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EP1282618A2 - 9-oxa-epothilon derivatives, method for the production and use thereof in pharmaceutical preparations - Google Patents

9-oxa-epothilon derivatives, method for the production and use thereof in pharmaceutical preparations

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Publication number
EP1282618A2
EP1282618A2 EP01927918A EP01927918A EP1282618A2 EP 1282618 A2 EP1282618 A2 EP 1282618A2 EP 01927918 A EP01927918 A EP 01927918A EP 01927918 A EP01927918 A EP 01927918A EP 1282618 A2 EP1282618 A2 EP 1282618A2
Authority
EP
European Patent Office
Prior art keywords
methyl
dihydroxy
dione
ethenyl
tetramethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01927918A
Other languages
German (de)
French (fr)
Inventor
Wolfgang Schwede
Ulrich Klar
Werner Skuballa
Bernd Buchmann
Jens Hoffmann
Rosemarie Lichtner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
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Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Publication of EP1282618A2 publication Critical patent/EP1282618A2/en
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • Epothilone A H
  • the aim of the structural changes is also to increase the therapeutic range. This can be achieved by improving the selectivity of the action and / or increasing the potency and / or reducing undesirable toxic side effects, as described in Proc. Natl. Acad. Be. USA 1998, 95, 9642-9647 are described.
  • Epothilone A The total synthesis of epothilone A is by Schinzer et al. in Chem. Eur. J. 1996, 2, No. 11, 1477-1482 and in Angew. Chem. 1997, 109, No. 5, pp. 543-544).
  • Epothilone derivatives have already been described by Höfle et al. described in WO 97/19086. These derivatives were made from natural epothilone A or B.
  • Epothilone derivatives partly also epothilones C and D are furthermore described in patent applications WO 99/07692, WO 99/02514, WO 99/01124, WO 99/67252, WO 98/25929, WO 97/19086, WO 98/38192, WO 99 / 22461 and WO 99/58534.
  • the object of the present invention is to provide new epothilone derivatives which are sufficiently stable both chemically and metabolically for drug development and which have a therapeutic breadth, their selectivity of action and / or undesirable toxic side effects and / or their Potency are superior to natural derivatives.
  • the present invention describes the new epothilone derivatives of the general formula I
  • R 9 is hydrogen, C ⁇ -C ⁇ Q-alkyl, aryl, C7-C20-aralkyl, C-
  • R3a is hydrogen, C- -C-Q-alkyl, aryl, C7-C20-aralkyl,
  • R 4 is hydrogen, C 1-8 alkyl, aryl, C7-C20 aralkyl
  • R 5 is hydrogen, CiC ⁇ Q-alkyl, aryl, C7-C20-aralkyl, halogen, cyano, (CH2) S -T where s is 1, 2, 3 or 4,
  • R "1 1 represents hydrogen or PG 1 1 ,
  • R6, R7 each represent a hydrogen atom, together an additional bond or an oxygen atom
  • G a group , a bi- or tricyclic aryl radical
  • R 12 is hydrogen, halogen, CN, C j -C20 alkyl, aryl, C7-C 20 aralkyl, which can all be substituted, X is an oxygen atom, two alkoxy groups OR ⁇ is a C2-CIQ-alkylene- ⁇ , co - Dioxy group, which can be straight-chain or branched, H / OR ⁇ 4 or a grouping CR 15 R 16 , wherein
  • R1 3 for a Cj-C20-alkyl radical
  • R " 14 for hydrogen or a protective group PG ⁇ 4 , R15 J R16 are identical or different and represent hydrogen, a C1-C20-alkyl, aryl, C7-C20-aralkyl radical,
  • R 17 is hydrogen, C-
  • R1 8 is hydrogen or a protective group PG " 1,
  • R 8 OH or OPG 8 shark halogen preferably fluorine, chlorine or bromine
  • A represents a C-j-Cg fragment (epothilone counting) of the general formula A-1 or A-2
  • R 1 a ', R 1 b ', R2a 'and R 2b ' those already mentioned for R 1 a , R 1 b , R 2a and R 2b
  • R 20 hydrogen, OR 20a , shark, OSO 2 R 20b , R 19a , R 20a hydrogen, S ⁇ 2-alkyl, SO2-A17I, S ⁇ 2-aralkyl or together one
  • R19b R 20b is hydrogen, C 1 -C 2 o-alkyl, aryl, C-
  • R 28a , R 23 are the same or different and are hydrogen, CjCj Q-alkyl, aryl,
  • R 21 is hydrogen
  • R 22 hydroxyl, or R21 R22 together represent an oxygen atom, or a C2-C-
  • Etherified or R21 J R22 are each a C j -C-Q-alkoxy group, including all stereoisomers and mixtures thereof, as well as mean free hydroxyl groups in R ⁇ 9, R 22 and R 2 ⁇ esterified, free carbonyl groups in A-1 or A-2 ketalized , converted into an enol ether or reduced and free acid groups in A-1 or A-2 in their salts with bases can be converted.
  • V is an oxygen atom, two alkoxy groups OR 23 , a C2-C-
  • W is an oxygen atom, two alkoxy groups OR 2 ⁇ , a C2-CiQ -Alkylene- ⁇ , ⁇ - dioxy group, which can be straight-chain or branched or H / OR 2 ⁇ ,
  • R 24 , R ⁇ independently of one another are hydrogen or a protective group PG 24 ,
  • R 23 , R ⁇ independently of one another are C 1 -C 20 -alkyl.
  • G ' is a group - ' , a bicyclic or tricyclic aryl radical
  • R ⁇ 2 ' has the meaning already given for R ⁇ 2 in the general formula I and R 7 ' is a hydrogen atom
  • R 27 halogen, N3, NHR 29 , a hydroxyl group, a protected hydroxyl group O-
  • R 28 is a hydroxy group, halogen, a protected hydroxy group OPG 28
  • X is an oxygen atom, two alkoxy groups OR ' ' 3 ', a C2-CiQ-alkylene- ⁇ , co-dioxy group, which can be straight-chain or branched, H / OR ⁇ 4 ' or a group CR15 R16 ', where R 13 ' is a C 1 -C 20 -alkyl radical,
  • R ' 5 , R 16 are the same or different and are hydrogen, a Cl-C20-alkyl
  • Aryl, C7-C20 aralkyl radical are mean.
  • the presentation of the new epothilone derivatives, in which R ⁇ is halogen or cyano, is based on the linkage of two partial fragments A and D.
  • the interfaces lie as indicated in the general formula I ".
  • A corresponds to the already described C-j-Cg fragment (epothilone counting) of the general formula A-1 or A-2.
  • R 5 is halogen or cyano and R 3a ", R 4 ", R 27 'and G" have the meanings already given for R 3a , R 4 , R 27 and G.
  • R 16 , R 6 ', R 19 , R 20b , R 23 , R 25 are straight or branched chain alkyl groups with 1-20 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl , Pentyl, isopentyl, neopentyl, heptyl, hexyl, decyl.
  • R15 ' ; R 16 , R16 ', Rl b , R 2 0, R 23 , R 23a , R 23 , R 2 5 can be perfluorinated or substituted be by 1-5 halogen atoms, hydroxyl groups, C ⁇ -C4-alkoxy groups, Cg-C ⁇ -
  • Aryl groups (which can be substituted by 1-3 halogen atoms).
  • R 0D , R 2 a , R b come substituted and unsubstituted carbocyclic or heterocyclic radicals with one or more heteroatoms such as phenyl, naphthyl, furyl, thienyl, pyridyl, pyrazolyl, pyrimidinyl, oxazolyl, pyridazinyl, pyrazinyl, quinolyl, thiazolyl, benzothiazolyl Benzoxazolyl, which can be mono- or polysubstituted by halogen, OH, O-alkyl, CO2H, CO 2 -alkyl, -NH2, -NO2, -N3, -CN, Cj-
  • C 20-alkyl, Cj-C20 acyl, Cj-C20-acyloxy groups, are suitable.
  • the bi- and tricyclic aryl radicals G are substituted and unsubstituted carbocyclic or heterocyclic radicals having one or more heteroatoms, such as, for example, naphthyl, anthryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolyl, isoquinolyl, benzoxazinyl, benzofuran, tololrahoxylolinolinolinolinylinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinylinolinolinolinolinolinylolinolinolinolinylolinolinolinylolinoxin Thienopyridinyl, pyridopyridinyl, benzopyrazolyl, benzotriazolyl, di
  • C 20 -alkyl, C j -C20 acyl, C ⁇ C20-acyloxy groups, are suitable.
  • the aralkyl groups in R a , R 1 , R 2a , R 2 , R 3a , R 4 , R 5 , R 9 , R 12 , R 15 , R 15 ', R 6 , R16' 7 Rl9b ⁇ 20b j 23a j R23b may contain up to 14 carbon atoms, preferably 6 to 10, and 1 to 8, preferably 1 to 4, atoms in the alkyl chain.
  • suitable aralkyl radicals are benzyl, phenylethyl, naphthylmethyl, naphthylethyl, furylmethyl, thienylethyl, pyridylpropyl.
  • the rings can be mono- or polysubstituted by halogen, OH, O-alkyl, CO2H, CO 2 -alkyl, -NO2, -N3, -CN, Cj-
  • -C20 acyl, Cj-C20 acyloxy groups The alkoxy groups contained in R 21 , R 22 and X in the general formula I are each intended to contain 1 to 20 carbon atoms, with methoxy, ethoxy-propoxy-isopropoxy and t-butyloxy groups being preferred.
  • Representing the protective groups PG are alkyl- and / or aryl-substituted silyl, Cj-
  • alkyl, silyl and acyl radicals for the protective groups PG are the radicals known to the person skilled in the art. Preferred are easily removable alkyl or silyl radicals from the corresponding alkyl and silyl ethers, such as, for example, methoxymethyl, methoxyethyl, ethoxyethyl, tetrahydropyranyl, tetrahydrofuranyl, Trimethylsilyl, triethylsilyl, tert.-butyldimethylsilyl, tert.-butyldiphenylsilyl, tribenzylsilyl, triisopropylsilyl, benzyl, para-nitrobenzyl, para-methoxybenzyl radicals and alkylsulfonyl and arylsulfonyl radicals.
  • suitable acyl radicals are formyl, acetyl, propionyl, isopropionyl, pivalyl,
  • residues known to the person skilled in the art are suitable as amino protective groups. Examples include the Alloc, Boc, Z, benzyl, f-Moc, Troc, stabase or benzostabase group.
  • the acyl groups PG can contain 1 to 20 carbon atoms, formyl, acetyl, propionyl, isopropionyl and pivalyl groups being preferred.
  • the index m in the alkylene group formed from R ⁇ a and R " " 3 is preferably 1, 2, 3 or 4.
  • the C2-C-JQ-alkylene, ⁇ -dioxy group which is possible for R 2 1, R 22 , V, W and X is preferably an ethylene ketal or neopentyl ketal group.
  • the partial fragments (synthesis building blocks) of the general formulas A-1 and A-2 can be prepared as in DE 197 51 200.3, DE 199 07 480.1, DE 199 21 0861.1 and WO 99/07692.
  • R ⁇ ' a can have all the meanings already mentioned for R ⁇ ' and can also be O-alkyl.
  • Step c (B-III ⁇ B-IV):
  • the aldehyde B-IV can be reduced.
  • the conversion into the aldehyde is carried out either directly, for example by reduction with diisobutylaluminum hydride at low temperatures (below -40 ° C.) or in two stages by reduction to alcohol and subsequent oxidation. Methods known to those skilled in the art are used for this.
  • complex hydrides such as lithium aluminum hydride are used for the reduction.
  • the oxidation can take place, for example, according to the methods described for the illustration of A-III.
  • Step d (B-IV »BV): by nucleophilic addition of organometallic compounds of the theoretical formula MR ⁇ ', in which M is indium, an alkali metal, preferably lithium or a divalent metal MX, in which X represents a halogen and the rest R' has the meanings given above.
  • M is indium
  • an alkali metal preferably lithium or a divalent metal
  • MX in which X represents a halogen and the rest R' has the meanings given above.
  • Magnesium and zinc are preferred as divalent metal, and chlorine, bromine and iodine are preferred as halogen X.
  • compounds of the type BV can also be obtained directly by nucleophilic addition. Methods known to those skilled in the art are used for this, such as the use of dialkyl copper lithium compounds.
  • compound B- can also be converted into partial fragments of type B analogously to WO 99/07692.
  • the partial fragments (synthesis building blocks) of the general formula C can be prepared as in DE 197 51 200.3, DE 199 07480.1 and WO 99/07692.
  • WO 99/07692 already proves the general applicability of the synthetic principle described below for the compounds according to the invention.
  • WO 99/07692 shows numerous synthesis building blocks of the general formulas A, B and C, with which further compounds of the general formula I claimed here can be obtained.
  • R ⁇ is a halogen atom, in particular a fluorine, chlorine or bromine atom, are the subject of DE 199 07 480.1 and PCT / EP00 / 01333.
  • Formula D-Il in which X can be a hydrogen and chG 2 can be a chiral auxiliary group, alkylated by the methods known to the person skilled in the art.
  • the enolate is produced by the action of strong bases such as lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures.
  • strong bases such as lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures.
  • Another possibility is a kind
  • Alcohols such as Pulegol, 2-phenylcyclohexanol, 2-hydroxy-1,2,2-triphenylethanol, 8-
  • Oxazolidinones are preferred, particularly preferably the compounds of the formulas D-lilac to D-Illd.
  • the choice of the respective antipode determines the absolute stereochemistry of the ⁇ -carbonyl carbon of the compound of the general formula D-IV.
  • the compounds of the general formulas D-IV to D-XV or their respective enantiomers ent-D-IV to ent-D-XV can be obtained enantiomerically pure. If an achiral alcohol such as ethanol is used as chG 2 -H (D-Ill); this gives the racemic compounds rac-D-IV to rac-D-XV.
  • Protecting groups PG15 are the protective groups known to the person skilled in the art, as have already been mentioned above for PG5 (A-1 ⁇ A-II).
  • Protective groups containing silicon which can be cleaved under acidic reaction conditions or using fluoride, such as e.g. the trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, tribenzylsilyl, triisopropylsilyl radical.
  • the tert-butyldiphenylsilyl and tert-butyldimethylsilyl radical is particularly preferred.
  • step a If the group chG 2 represents one of the chiral auxiliary groups mentioned under step a, this is recovered by transesterification of D-IV into an alkyl ester of the general formula DV.
  • the transesterification takes place according to the methods known to the person skilled in the art. Transesterification with simple alcohols such as methanol or ethanol in the presence of corresponding titanium (IV) alcoholates is preferred.
  • Step c (DN ⁇ D-VI):
  • Suitable reducing agents are the reducing agents known to the person skilled in the art, e.g. Aluminum hydrides such as Lithium aluminum hydride or diisobutyl aluminum hydride.
  • Aluminum hydrides such as Lithium aluminum hydride or diisobutyl aluminum hydride.
  • the reaction takes place in an inert solvent such as e.g. Diethyl ether, tetrahydrofuran, toluene.
  • the carbonyl group in D-IV can be reduced directly to the alcohols of the general formula D-VI under the conditions mentioned under step c).
  • the chiral auxiliary component chG -H can also be recovered here.
  • Tetrapropylammonium perruthenate in inert solvents Oxidation according to Swern, S ⁇ 3-pyridine complex and with N-methyl-morpholino-N-oxide using tetrapropylammonium perruthenate is preferred.
  • the unsaturated esters of the general formula D-VIII are produced by the processes known to the person skilled in the art. Methods such as the Wittig or Wittig / Horner reaction or the Peterson olefination are suitable for this.
  • the Wittig / Horner reaction is preferred using phosphonates of the alkylOOC-CHR5 "-P (O) (OAIkyl ') 2 type, where alkyl and alkyl' may be the same or different and are preferably methyl, ethyl, i-propyl or trifluoroethyl and R5 'has the meaning already mentioned, with bases such as, for example, potassium carbonate, sodium hydride, n-butyllithium, potassium tert-butanolate, sodium ethanolate, lithium hexamethyldisilazane, sodium hexamethyldisilazane, potassium hexamethyldisilazane and, if appropriate, with additions of, for example, crown
  • the E / Z diastereomers obtained can, for example, be separated at this or the next stage and can be converted individually into the corresponding E or Z olefin end products.
  • E-form is shown in the formula diagram. However, all of the following steps also apply to the corresponding Z isomer.
  • Type D-IX transferred is based on a multi-stage process.
  • the ester function in D-VIII can be reduced to a primary alcohol.
  • Suitable reducing agents are the reducing agents known to the person skilled in the art, such as, for example, aluminum hydrides such as, for example, lithium aluminum hydride or diisobutyl aluminum hydride.
  • the reaction takes place in an inert solvent such as diethyl ether, tetrahydrofuran, toluene.
  • the primary alcohol can then be converted into a leaving group, such as a halide or an OSO 2 alkyl, O-SO 2 aryl or OS ⁇ 2 aralkyl group.
  • the later C-14 can then be introduced, for example, by substitution with cyanide using NaCN or KCN.
  • the nitrile formed is then converted into an aldehyde by reduction with, for example, diisobutylaluminum hydride and acid cleavage of the primarily formed imine, which is then converted into the primary alcohol of type D-IX, for example with lithiumaluminum hydride, sodium borohydride or diisobutylaluminum hydride.
  • triphenylphosphine and azodiesters such as
  • OS ⁇ 2Aryl or OS ⁇ 2Araikyl group are transferred.
  • the escape group is preferably formed on the primary alcohol function in building block D-IX.
  • the free hydroxyl group in the other building block, preferably B-II is then mixed with suitable bases such as, for example, sodium hydride, n-butyllithium, 4-dimethylaminopyridine, Hünig base,
  • Step h (DX ⁇ D-Xl):
  • the protective group PG 7 is now split according to the methods known to the person skilled in the art. If it is an acidic cleavable protective group, dilute mineral acids in aqueous alcoholic solutions are suitable, the use of catalytic amounts of acids such as para-toluenesulfonic acid, para-toluenesulfonic acid pyridinium salt, camphorsulfonic acid in alcoholic solutions, preferably in ethanol or isopropanol.
  • a in the compounds of the formula I is an NR ⁇ 7 group
  • the protective group PG 7 is first split selectively by the methods known to the person skilled in the art (see also above) , The secondary alcohol thus obtained is converted with a sulfonyl chloride or a
  • Halides or sulfonates can then be replaced by a nucleophilic substitution with e.g. B.
  • the oxidation of the primary alcohol in D-Xl to the corresponding aldehyde takes place according to the methods known to the person skilled in the art. Examples include oxidation with pyridinium chlorochromate, pyridinium dichromate, chromium trioxide-pyridine complex, oxidation according to Swern or related methods, e.g. using SO3-
  • R 3a " ⁇ H can now by the methods known to those skilled in the art with organometallic compounds of the general formula MR 3a ", where M is an alkali metal, preferably lithium or a divalent metal MX, where X represents a halogen and the radical R 3a "has the meaning given above, the corresponding secondary alcohol is prepared.
  • M is an alkali metal, preferably lithium or a divalent metal MX, where X represents a halogen and the radical R 3a "has the meaning given above
  • the corresponding secondary alcohol is prepared.
  • Magnesium and zinc are preferred as the divalent metal
  • chlorine, bromine and iodine are preferred as the halogen X.
  • the secondary alcohol obtained in this way is converted by oxidation into the ketone of the general formula D with R3 'nach H according to the processes mentioned under i) at the beginning. Oxidation with N-methylmorpholino-N-oxide using tetrapropylammonium perruthenate is preferred.
  • RH R ⁇ ', R 2a ', R 2b ', R 3a ', R 4 ', ⁇ ' , R1 9 , R 2 0, R 2 " !, R 22 V and Z have the meanings already mentioned and PG 7 represents a hydrogen atom or a protective group PG, are obtained from the aforementioned fragments A and B by the method shown in Scheme 3.
  • the compound B in which W has the meaning of an oxygen atom and any additional carbonyl groups present are protected, is alkylated with the enolate of a carbonyl compound of the general formula A.
  • the enolate is formed by the action of strong bases such as e.g. Lithium diisopropylamide, lithium hexamethyldisilazane produced at low temperatures.
  • the compound C in which R 23 has the meaning of a Wittig salt and any additional carbonyl groups which may be present are protected, is deprotonated by a suitable base such as, for example, n-butyllithium, lithium diisopropylamide, potassium tert-butoxide, sodium or lithium hexamethyldisilazide and with a compound B, in which V the
  • the compound C in which R 23 has the meaning of a Wittig salt and any additional carbonyl groups that may be present are protected, is deprotonated by a suitable base, such as, for example, n-butyllithium, lithium diisopropylamide, potassium tert-butoxide, sodium or lithium hexamethyldisilazide, and with a compound AB, where V has the meaning of an oxygen atom, implemented.
  • a suitable base such as, for example, n-butyllithium, lithium diisopropylamide, potassium tert-butoxide, sodium or lithium hexamethyldisilazide, and with a compound AB, where V has the meaning of an oxygen atom, implemented.
  • the compound BC in which W has the meaning of an oxygen atom and any additional carbonyl groups which may be present are protected, is alkylated with the enolate of a carbonyl compound of the general formula A.
  • the enolate is produced by the action of strong bases such as lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures. Representation of the partial fragments AD:
  • the compound D is alkylated with the enolate of a carbonyl compound of the general formula A.
  • the enolate is formed by the action of strong bases such as e.g. Lithium diisopropylamide, lithium hexamethyldisilazane produced at low temperatures.
  • the fragments ABC and AD are converted into compounds of the general formula I by the processes described below.
  • the only difference between the fragments ABC and AD is that in the fragments ABC the residue R5 'can raise all meanings of R ⁇ except halogen and cyano, while in the fragments AD Rp "means halogen or cyano.
  • preferred for lactone formation is the method described in "Reagents for Organic Synthesis, Vol. 16, p 353"
  • Triethylamine 4-dimethylaminopyridine, sodium hydride.
  • Triethylamine 4-dimethylaminopyridine, sodium hydride.
  • Lactam formation is the implementation of the amino acid (R ⁇ 9 a carboxylic acid and CO2H
  • R 27 is an NHR 29 group) with diphenylphosphoryl azide in the presence of a base.
  • suitable bases such as sodium hydride, n-butyllithium, 4-dimethylaminopyridine, Hünig base, Cyclize alkylihexamethyldisilazanes to compounds of formula I in which AY has the meaning of an O-CH2 group.
  • Oxygen atom and R 27 represents an NR 29 S ⁇ 2CH3 ⁇ group, can be
  • Group has, cyclize.
  • phosphine such as triphenyiphosphine in the presence of water
  • the azide can be introduced using the Mitsunobu reaction in the presence of metal azides, preferably sodium or zinc azide or by substitution of one suitable leaving group such as a chlorine, bromine or iodine atom, an alkylsulfonyloxy, a perfluorinated alkylsulfonyloxy, an arylsulfonyloxy or an aralkylsulfonyloxy group by azides.
  • metal azides preferably sodium or zinc azide or by substitution of one suitable leaving group such as a chlorine, bromine or iodine atom, an alkylsulfonyloxy, a perfluorinated alkylsulfonyloxy, an arylsulfonyloxy or an aralkylsulfonyloxy group by azides.
  • Free hydroxyl groups in I, A, B, C, AB, BC, ABC can be etherified or
  • Esterification, free carbonyl groups can be further functionally modified by ketalization, enol ether formation or reduction.
  • the invention relates to all stereoisomers of these compounds and also theirs
  • the invention further relates to all prodrug formulations of these compounds, ie all compounds which release a bioactive active ingredient component of the general formula I in vivo.
  • the new compounds of formula I are valuable pharmaceuticals. They interact with tubulin by stabilizing formed microtubules and are therefore able to influence cell division in a phase-specific manner. This concerns above all fast growing, neoplastic cells, the growth of which is largely unaffected by intercellular control mechanisms.
  • active substances of this type are suitable for the treatment of malignant tumors. Areas of application include the therapy of ovarian, stomach, colon, adeno, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia.
  • the compounds according to the invention are suitable in principle for anti-angiogenesis therapy and for the treatment of chronic inflammatory diseases such as, for example, psoriasis, multiple sclerosis or arthritis.
  • chronic inflammatory diseases such as, for example, psoriasis, multiple sclerosis or arthritis.
  • they can in principle be applied or incorporated into the polymeric materials used for this.
  • the compounds according to the invention can be used alone or to achieve them.
  • additive or synergistic effects can be used in combination with other principles and substance classes applicable in tumor therapy. Examples include the combination with
  • Platinum complexes such as Cisplatin, carboplatin,
  • Intercalating substances e.g. from the class of anthracyclines such as Doxorubicin or from the class of antrapyrazoles such as e.g. CI-941,
  • Substances interacting with tubulin e.g. from the class of Vinka alkaloids such as Vincristine, vinblastine or from the taxane class such as Taxol, Taxotere or from the macrolide class such as e.g. Rhizoxin or other compounds such as e.g. Colchicine, combretastatin A-4, discodermolide and its analogues,
  • DNA topoisomerase inhibitors such as e.g. Camptothecin, etoposide, topotecan, teniposide, folate or pyrimidine antimetabolites such as e.g. Lometrexol, gemcitubin,
  • DNA alkylating compounds such as e.g. Adozelesin, dystamycin A,
  • Inhibitors of growth factors e.g. PDGF, EGF, TGFb, EGF
  • growth factors e.g. PDGF, EGF, TGFb, EGF
  • Somatostatin e.g. Somatostatin, suramin, bombesin antagonists
  • Inhibitors of protein tyrosine kinase or protein kinases A or C such as erbstatin, genistein, staurosporin, llmofosin, 8-CI-cAMP, Anti-hormones from the class of antigestagens such as mifepristone, onapristone or from the class of anti-estrogens such as tamoxifen or from the class of anti-androgens such as cyproterone acetate,
  • Metastasis inhibiting compounds e.g. from the class of eicosanoids such as PGI2, PGE ⁇ , 6-oxo-PGE-
  • as well as their stable derivatives e.g. Iloprost,
  • Inhibitors of oncogenic RAS proteins which influence mitotic signal transduction for example inhibitors of farnesyl protein transferase,
  • Natural or artificially produced antibodies which are directed against factors or their receptors which promote tumor growth such as the erbB2 antibody.
  • the invention also relates to pharmaceuticals based on the pharmaceutically acceptable, i.e. in the doses used, non-toxic compounds of the general formula I, if appropriate together with the customary auxiliaries and carriers.
  • the compounds according to the invention can be encapsulated with liposomes or enclosed in an ⁇ -, ⁇ - or ⁇ -cyclodextrin clathrate.
  • the compounds according to the invention can be processed into pharmaceutical preparations for enteral, percutaneous, parenteral or local application according to known galenical methods. They can be administered in the form of tablets, dragees, gel capsules, granules, suppositories, implants, injectable sterile aqueous or oily solutions, suspensions or emulsions, ointments, creams and gels.
  • the active ingredient (s) can be combined with the auxiliary agents commonly used in galenics, e.g.
  • compositions which contain at least one compound according to the invention as active ingredient.
  • One dose unit contains about 0.1-100 mg of active ingredient (s).
  • the dosage of the compounds according to the invention in humans is about 0.1-1000 mg per day.
  • Example 1 serve to explain the invention in more detail without wishing to restrict it:
  • Dichloromethane is added at -70 ° C a solution of 5.99 ml (85.25 mmol) of dimethyl sulfoxide in 10 ml of dichloromethane. The mixture is stirred for 3 minutes at -70 ° C and then a solution of 6.204g (28.41 mmol) 1c in 100 ml dichloromethane is added. The mixture is stirred for a further 30 minutes at -70 ° C. Then 31.5 ml (227.36 mmol) of triethylamine are added and the mixture is left to react at -50 ° C. for 30 minutes. The reaction mixture is then poured onto saturated aqueous sodium bicarbonate solution. It is extracted with dichloromethane. The organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The crude product obtained (6.15 g, 100%) is used in the next step without purification.
  • the mixture is then stirred at 0 ° C for 3 hours.
  • the reaction mixture is then poured onto saturated aqueous ammonium chloride solution. It is extracted with ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate.
  • the crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 1.043 g (1.98 mmol; 30%) of the title compound A and 870 mg (1.65 mmol; 25%) of the title compound B are obtained.
  • Lithium diisopropylamide is prepared in 20 ml of absolute tetrahydrofuran from 473 mg (3.37 mmol) of diisopropylamine and 1.37 ml (3.41 mmol) of a 2.5 molar solution of butyllithium in hexane.
  • a solution of 1.273 g (3.16 mmol) of (3S) -1,3-bis [[dimethyl (1,1-dimethylethyl) silyl] oxy] -4,4-dimethylheptane is then added at -70 ° C. -5- one in 15 ml of tetrahydrofuran and allowed to stir for one hour at -40 to -30 ° C.
  • Example 1m (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-1-ol
  • a solution of 527 mg (0.55 mmol) 11 and 128 mg ( 0.55 mmol) camphor-10-sulfonic acid in 20 ml of a 1: 1 mixture of dichloromethane and methanol is stirred at 25 ° C. for 2 hours.
  • Example 1n (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12-pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-1-al
  • the substance is used in the next stage without purification.
  • 1 H NMR (CDCI3): ⁇ 0.02-0.13 (18H), 0.83-0.92 (27H), 1.02 (3H), 1.09 (3H), 1.11
  • Example 1p (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -3,7-bis [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -16-fluoro-15-hydroxy-17- (2nd -methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12-pentamethyl-12, 16-dienoic acid
  • a solution of 345 mg (0.40 mmol) 10 in 15 ml of tetrahydrofuran is 6 ml of a 1 molar solution of tetrabutylammonium fluoride in tetrahydrofuran were added. The mixture is left to stir at 25 ° C.
  • 530 ⁇ l of HF-pyridine complex are added at 0 ° C. to a solution of 169 mg (0.23 mmol) of the compound described under 1q in 10 ml of tetrahydrofuran. The mixture is stirred at 25 ° C. for one hour and then 530 ⁇ l of HF-pyridine complex are added again. Then allowed to stir at 25 ° C for 10 hours. The reaction mixture is then poured onto saturated aqueous sodium hydrogen carbonate solution. It is extracted with dichloromethane, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate.
  • Example 3 4S, 7R, 8S, 9R, 13 (E), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ) ethenyl) -5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dione
  • 175 mg (0.24 mmol) of the compound described under 3i becomes 85 mg (0.17 mmol, 71%) of the title compound.

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Abstract

The invention relates to novel epothilon derivatives which are characterized by an oxygen atom in position 9 of the epothilon skeleton. The novel compounds interact with tubulin, stabilizing formed microtubuli. They can influence cell division in a phase-specific manner and are suitable for use in the treatment of malignant tumors such as ovarian, stomach, colon, adeno, breast, lungs, head and neck carcinoma, malignant melanoma, acute lymphocytic and myelocytic leukaemia. They are also suitable for anti-angiogenesis thereapy and for use in the treatment of chronic inflamatory diseases (psoriasis, arthritis). In order to avoid uncontrolled proliferation of cells on and to improve the compatibility of medical implants, they can be placed on or in polymer materials. The inventive compounds can be used on their own or to obtain additive or synergistic effects in combination with other classes of substances and principles which can be used in tumoral therapy.

Description

9-Oxa-Epothi Ion-Derivate, Verfahren zu deren Herstellung sowie ihre Verwendung in pharmazeutischen Präparaten9-Oxa-Epothi ion derivatives, process for their preparation and their use in pharmaceutical preparations

Von Höfle et ai. wird die cytotoxische Wirkung der Naturstoffe Epothilon A (R = Wasserstoff) und Epothilon B (R = Methyl)By Höfle et ai. the cytotoxic effects of the natural substances epothilone A (R = hydrogen) and epothilone B (R = methyl)

Epothilon A (R = H), Epothilon B (R=CH3)Epothilone A (R = H), epothilone B (R = CH 3 )

z.B. in Angew. Chem. 1996, 108, 1671-1673, beschrieben. Wegen der in-vitro- Selektivität gegenüber Brust- und Darmzelllinien und ihrer im Vergleich zu Taxol deutlich höheren Aktivität gegen P-GIycoprotein-bildende, multiresistente Tumorlinien sowie ihre gegenüber Taxol verbesserten physikalischen Eigenschaften, z.B eine um den Faktor 30 höhere Wasserlöslichkeit, ist diese neuartige Strukturklasse für die Entwicklung eines Arzneimittels zur Therapie maligner Tumoren besonders interessant. Die Naturstoffe sind sowohl chemisch als auch metabolisch für eine Arzneimittelentwicklung nicht ausreichend stabil. Zur Beseitigung dieser Nachteile sind Modifikationen an dem Naturstoff nötig. Derartige Modifikationen sind nur auf totalsynthetischem Wege möglich und setzen Synthesestrategien voraus, die eine breite Modifikation des Naturstoffes ermöglichen. Ziel der Strukturveränderungen ist es auch, die therapeutische Breite zu erhöhen. Dies kann durch eine Verbesserung der Selektivität der Wirkung und/oder eine Erhöhung der Wirkstärke und/oder eine Reduktion unerwünschter toxischer Nebenwirkungen, wie sie in Proc. Natl. Acad. Sei. USA 1998, 95, 9642-9647 beschrieben sind, erfolgen.e.g. in Angew. Chem. 1996, 108, 1671-1673. Because of the in vitro selectivity towards breast and intestinal cell lines and their significantly higher activity against P-glycoprotein-forming, multi-resistant tumor lines compared to Taxol as well as their improved physical properties compared to Taxol, e.g. a 30 times higher water solubility, this is new Structural class of particular interest for the development of a drug for the treatment of malignant tumors. The natural products are not sufficiently stable both chemically and metabolically for drug development. Modifications to the natural product are necessary to eliminate these disadvantages. Such modifications are only possible in a totally synthetic way and presuppose synthesis strategies that enable a broad modification of the natural product. The aim of the structural changes is also to increase the therapeutic range. This can be achieved by improving the selectivity of the action and / or increasing the potency and / or reducing undesirable toxic side effects, as described in Proc. Natl. Acad. Be. USA 1998, 95, 9642-9647 are described.

Die Totalsynthese von Epothilon A ist von Schinzer et al. in Chem. Eur. J. 1996, 2, No. 11, 1477-1482 und in Angew. Chem. 1997, 109, Nr. 5, S. 543-544) beschrieben. Epothilon-Derivate wurden bereits von Höfle et al. in der WO 97/19086 beschrieben. Diese Derivate wurden ausgehend vom natürlichen Epothilon A oder B hergestellt. Auch Epothilon C und D (Doppelbindung zwischen den Kohlenstoffatomen 12 und 13: Epothilon C = Desoxyepothilon A; Epothilon D = Desoxyepothilon B) sind als mögliche Ausgangsprodukte hierfür beschrieben. Eine weitere Synthese von Epothilon und Epothilonderivaten wurde von Nicolaou et al. in Angew. Chem. 1997, 109, Nr. 1/2, S. 170 - 172 beschrieben. Die Synthese von Epothilon A und B und einiger Epothilon-Analoga wurde in Nature, Vol. 387, 1997, S. 268-272, die Synthese von Epothilon A und seinen Derivaten in J. Am. Chem. Soc, Vol. 119, No. 34, 1997, S. 7960 - 7973 sowie die Synthese von Epothilon A und B und einiger Epothilon-Analoga in J. Am. Chem. Soc, Vol. 119, No. 34, 1997, S. 7974 - 7991 ebenfalls von Nicolaou et al. beschrieben.The total synthesis of epothilone A is by Schinzer et al. in Chem. Eur. J. 1996, 2, No. 11, 1477-1482 and in Angew. Chem. 1997, 109, No. 5, pp. 543-544). Epothilone derivatives have already been described by Höfle et al. described in WO 97/19086. These derivatives were made from natural epothilone A or B. Epothilones C and D (double bond between carbon atoms 12 and 13: epothilone C = deoxyepothilone A; epothilone D = deoxyepothilone B) are also described as possible starting products for this. Another synthesis of epothilone and epothilone derivatives was by Nicolaou et al. in Angew. Chem. 1997, 109, No. 1/2, pp. 170-172. The synthesis of epothilones A and B and some epothilone analogues was described in Nature, Vol. 387, 1997, pp. 268-272, the synthesis of epothilone A and its derivatives in J. Am. Chem. Soc, Vol. 119, No. 34, 1997, pp. 7960-7973 and the synthesis of epothilones A and B and some epothilone analogues in J. Am. Chem. Soc, Vol. 119, No. 34, 1997, pp. 7974-7991 also by Nicolaou et al. described.

Ebenfalls Nicolaou et al. beschreiben in Angew. Chem. 1997, 109, Nr. 19, S. 2181-2187 die Herstellung von Epothilon A-Analoga mittels kombinatorischer Festphasensynthese. Auch einige Epothilon B-Analoga sind dort beschrieben.Nicolaou et al. describe in Angew. Chem. 1997, 109, No. 19, pp. 2181-2187 the preparation of epothilone A analogues by means of combinatorial solid phase synthesis. Some epothilone B analogues are also described there.

Epothilon-Derivate, z.T. auch Epothilon C und D, sind des weiteren in den Patentanmeldungen WO 99/07692, WO 99/02514, WO 99/01124, WO 99/67252, WO 98/25929, WO 97/19086, WO 98/38192, WO 99/22461 und WO 99/58534 beschrieben.Epothilone derivatives, partly also epothilones C and D are furthermore described in patent applications WO 99/07692, WO 99/02514, WO 99/01124, WO 99/67252, WO 98/25929, WO 97/19086, WO 98/38192, WO 99 / 22461 and WO 99/58534.

Die Aufgabe der vorliegenden Erfindung besteht darin, neue Epothilon-Derivate zur Verfügung zu stellen, die sowohl chemisch als auch metabolisch für eine Arzneimittelentwicklung ausreichend stabil sind und die hinsichtlich ihrer therapeutischen Breite, ihrer Selektivität der Wirkung und/oder unerwünschter toxischer Nebenwirkungen und/oder ihrer Wirkstärke den natürlichen Derivaten überlegen sind.The object of the present invention is to provide new epothilone derivatives which are sufficiently stable both chemically and metabolically for drug development and which have a therapeutic breadth, their selectivity of action and / or undesirable toxic side effects and / or their Potency are superior to natural derivatives.

Die vorliegende Erfindung beschreibt die neuen Epothilon-Derivate der allgemeinen Formel I,The present invention describes the new epothilone derivatives of the general formula I

l, worin R^a, R^b gleich oder verschieden sind und Wasserstoff, C-j-C-in-Alkyl, Aryl, C7- C-20-Aralkyl, oder gemeinsam eine -(CH2)m-Gruppe mit m = 1 , 2, 3, 4 oder 5, oder eine -(CH2)-O-(CH2)-Gruppe,l, in which R ^ a , R ^ b are the same or different and are hydrogen, C- j- C-in-alkyl, aryl, C7-C-20-aralkyl, or together a - (CH2) m group with m = 1, 2 , 3, 4 or 5, or a - (CH2) -O- (CH2) group,

R2a,R2b gleich oder verschieden sind und Wasserstoff, C-j -C^ Q-Alkyl, Aryl, C7-C20- Aralkyl, -(CH2)rC≡C-(CH2)p-R9, -(CH2)rC=C-(CH2)p-R9, r gleich 0 bis 4, p gleich 0 bis 3,R2 a , R2b are the same or different and are hydrogen, C- j -C ^ Q-alkyl, aryl, C7-C20-aralkyl, - (CH 2 ) rC≡C- (CH 2 ) pR 9 , - (CH2) r C = C- (CH 2 ) pR 9 , r is 0 to 4, p is 0 to 3,

R9 Wasserstoff, C^-C^ Q-Alkyl, Aryl, C7-C20-Aralkyl, C-|-Cιo-Acyl, oder, falls p>0 ist, auch eine Gruppe OR^O, R10 Wasserstoff, eine Schutzgruppe PG 0,R 9 is hydrogen, C ^ -C ^ Q-alkyl, aryl, C7-C20-aralkyl, C- | -Cιo-acyl, or, if p> 0, also a group OR ^ O, R 10 hydrogen, a protective group PG 0 ,

R3a Wasserstoff, C- -C-j Q-Alkyl, Aryl, C7-C20-Aralkyl,R3a is hydrogen, C- -C-Q-alkyl, aryl, C7-C20-aralkyl,

R3b OH, OPG3 R 3b OH, OPG 3

R4 Wasserstoff, C^-Ci fj-Alkyl, Aryl, C7-C20-AralkylR 4 is hydrogen, C 1-8 alkyl, aryl, C7-C20 aralkyl

R5 Wasserstoff, C-i-C^ Q-Alkyl, Aryl, C7-C20-Aralkyl, Halogen, Cyano, (CH2)S-T wobei s für 1 , 2, 3 oder 4,R 5 is hydrogen, CiC ^ Q-alkyl, aryl, C7-C20-aralkyl, halogen, cyano, (CH2) S -T where s is 1, 2, 3 or 4,

T für OR1 1 oder Hai,T for OR 1 1 or shark,

R"1 1 für Wasserstoff oder PG1 1 stehen,R "1 1 represents hydrogen or PG 1 1 ,

R6, R7 je ein Wasserstoffatom, gemeinsam eine zusätzliche Bindung oder ein Sauerstoffatom,R6, R7 each represent a hydrogen atom, together an additional bond or an oxygen atom,

G eine Gruppe , ein bi- oder tricyclischer Arylrest,G a group , a bi- or tricyclic aryl radical,

R12 Wasserstoff, Halogen, CN, C-j-C20-Alkyl, Aryl, C7-C-20-Aralkyl, die alle substituiert sein können, X ein Sauerstoffatom, zwei Alkoxygruppen OR^ eine C2-CiQ-Alkylen-α,co- dioxygruppe, die geradkettig oder verzweigt sein kann, H/OR^4 oder eine Gruppierung CR15R16, wobeiR 12 is hydrogen, halogen, CN, C j -C20 alkyl, aryl, C7-C 20 aralkyl, which can all be substituted, X is an oxygen atom, two alkoxy groups OR ^ is a C2-CIQ-alkylene-α, co - Dioxy group, which can be straight-chain or branched, H / OR ^ 4 or a grouping CR 15 R 16 , wherein

R13 für einen C-j -C20-Alkylrest,R1 3 for a Cj-C20-alkyl radical,

R"l4 für Wasserstoff oder eine Schutzgruppe PG^4, R15J R16 gleich oder verschieden sind und für Wasserstoff, einen C1-C20- Alkyl-, Aryl-, C7-C20-Aralkylrest stehen,R " 14 for hydrogen or a protective group PG ^ 4 , R15 J R16 are identical or different and represent hydrogen, a C1-C20-alkyl, aryl, C7-C20-aralkyl radical,

A-Y eine Gruppe O-C(=O), O-CH2, CH2C(=O), NR17-C(=O), NR 7-SO2,AY a group OC (= O), O-CH 2 , CH 2 C (= O), NR 17 -C (= O), NR 7 -SO 2 ,

R17 Wasserstoff, C-| -C^ o-Alkyl, Z ein Sauerstoffatom oder H/OR18, wobeiR 17 is hydrogen, C- | -C ^ o-alkyl, Z is an oxygen atom or H / OR 18 , wherein

R18 Wasserstoff oder eine Schutzgruppe PG"1 ist,R1 8 is hydrogen or a protective group PG " 1,

R8 OH oder OPG8 Hai Halogen, vorzugsweise Fluor, Chlor oder Brom bedeutetR 8 OH or OPG 8 shark halogen, preferably fluorine, chlorine or bromine

ausgenommen derjenigen Verbindungen, in denen R2a Wasserstoff ist und R^b Wasserstoff, Alkyl oder Aryl und gleichzeitigexcluding those compounds in which R 2a is hydrogen and R ^ b is hydrogen, alkyl or aryl and simultaneously

R5 Wasserstoff, Alkyl oder Aryl und gleichzeitig A-Y eine Gruppierung O-C(=O), O-CH2 oder NR17-C(=O) und gleichzeitigR5 is hydrogen, alkyl or aryl and at the same time AY is a grouping OC (= O), O-CH 2 or NR 17 -C (= O) and simultaneously

G einen bi- oder tricyclischen Arylrest oder eine Gruppierung X=(CRl2)-bedeuten, wobei alle anderen Reste die angegebenen Bedeutungen haben können.G is a bi- or tricyclic aryl radical or a grouping X = (CRl2), where all other radicals can have the meanings given.

Durch den Disciaimer werden die in der WO 99/02514 beanspruchten Verbindungen ausgeschlossen.The compounds claimed in WO 99/02514 are excluded by the disc bucket.

Die nachstehend genannten Verbindungen sind erfindungsgemäß bevorzugt:The compounds mentioned below are preferred according to the invention:

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1-fluor-2-(2-methyl-4- thiazo!yl)ethenyl)- 5,5,7,9,13-pentamethyl-cyc!ohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazo! yl) ethenyl) - 5,5,7,9,13-pentamethyl-cyc! ohexadec-13-en-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8, 8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8, 8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclo [14.1. Ojheptadecan 5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-7-ethyl-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-7-ethyl-16- (1-fluoro-2- (2-methyl- 4-thiazolyl) ethenyl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -5,5,9,13-tetramethyl-dione cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)- 5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-7-ethyl-16-(1-fluor-2-(2- methyloxazol-4-yl)ethenyl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-jdion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-7-ethyl-16- (1-fluoro-2- (2-methyloxazole- 4-yl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-jdione

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1 -fluor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl ) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-pyridyl)ethenyl)- 5,5,7,9, 13-pentamethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 5 , 5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)- 8,8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclot14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) - 8.8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclot14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-7-ethyl-16-(1-fluor-2-(2- pyridyl)ethenyl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-10-ethyl-3-(1 -f!uor-2-(2- pyridyl)ethenyl)-8,8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-7-ethyl-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11 -dihydroxy-10-ethyl-3- (1 -f! Uor-2- (2-pyridyl) ethenyl) - 8,8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-fluor-2-(2-pyridyl)ethenyl)- 7-(prop-2-en-1 -yl)- 5,5,9, 13-tetramethyl-cycIohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 7 - (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) -10- (prop-2-ene -1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12,16-pentamethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -fluor-2-(2-methyI-4-thiazolyl)ethenyl)- 7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyI-cycIohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cycIohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -fluor-2-(2-methyloxazol-4-yl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyloxazol-4-yl)ethenyl)- 7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1 -yl)-8,8,12, 16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -f luor-2-(2-pyridyl)ethenyl)-1 -aza-10- oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1 -f luor-2- (2-pyridyl) ethenyl) -1 -aza-10- oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)- 8,8, 10, 12, 16-pentamethyl-4-aza-13, 17-dioxabicyclo[14.1.0]hep.adecan-5j,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) - 8.8, 10, 12, 16-pentamethyl-4-aza-13, 17-dioxabicyclo [14.1.0] hep.adecan-5j, 9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1-fluor-2-(2-pyridyl)ethenyl)-1- aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-fluoro-2- (2-pyridyl) ethenyl) -1- aza -10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2- pyridyl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-pyridyl) ethenyl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-pyridyl)ethenyl)-7-(prop-2- en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-pyridyl) ethenyl) -7- (prop-2- en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-3-(1 -fluor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1 -yl)-8,8, 12,16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1 -yl) -8.8, 12,16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecanoic

5,9-dion5,9-dione

(4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-7-ethyI-16-(1 -chlor-2-(2-methyl- 4-thiazolyl)ethenyl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-7-ethyI-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chIor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4,13, 17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12, 16-tetramethyl-4,13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)- 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-3-(1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -8, 8,10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-7-ethyl-16-(1-chlor-2-(2- methyloxazol-4-yl)ethenyl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-7-ethyl-16- (1-chloro-2- (2-methyloxazole- 4-yl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2-methyloxazol- 4-yi)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyloxazol-4-yi) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

f 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa16-(1-chlor-2-(2-pyridyl)ethenyl)- 5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dionf 1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa16- (1-chloro-2- (2-pyridyl) ethenyl) - 5.5 , 7,9,13--pentamethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -chlor-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4,13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) - 8,8,10, 12,16-pentamethyl-4,13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-7-ethyl-16-(1-chlor-2-(2- pyridyl)ethenyl)- 5,5,9,13-tetramethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-7-ethyl-16- (1-chloro-2- (2-pyridyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2- pyridyl)ethenyl)-8,8, 12, 16-tetramethyl-4, 13, 7-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-pyridyl) ethenyl) -8.8, 12, 16-tetramethyl-4, 13, 7-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-chlor-2-(2-pyridyl)ethenyl)- 7-(prop-2-en-1-yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-16- (1-chloro-2- (2-pyridyl) ethenyl) - 7 - (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione

{1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1 -chlor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion{1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11 -dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyl-4-thiazolyl)ethenyl)- 1 -aza-10-oxa-5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyl-4-thiazolyI)ethenyl)- 7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazolyI) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyloxazoI-4-yl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyloxazoI-4-yl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione

( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -8, 8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chIor-2-(2-methyIoxazol- 4-yl)ethenyl)-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyloxazol-4-yl)ethenyl)- 7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1 -chlor-2-(2-pyridyl)ethenyl)-1 -aza-10- oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-pyridyl) ethenyl) -1-aza-10-oxa -5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione

( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -chior-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) - 8,8,10, 12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyI-16-(1-chlor-2-(2-pyridyl)ethenyl)-1- aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-pyridyl) ethenyl) -1- aza -10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chIor-2-(2- pyridyl)ethenyl)-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-pyridyl) ethenyl) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-pyridyl)ethenyl)-7-(prop-2- en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-pyridyI)ethenyl)-10-(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-pyridyl) ethenyl) -7- (prop-2- en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) -10-

(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(prop-2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-methyl-4- thiazo!yl)ethenyl)- 7,9,13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazo! yl) ethenyl) - 7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-deca-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-deca-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-7-ethyl-16-(1- fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-7-ethyl-16- (1-fluoro-2 - (2-methyl-4-thiazolyl) ethenyl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-10-ethyl-3-(1-fluor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1 ,3-trimethylen)-4,13,17-trioxabicyclo[14.1.Ojhepta- decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-10-ethyl-3- (1-fluoro-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.Ojhepta-decan-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(1-fluor-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-fluoro-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-fluor-2-(2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione

4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1 -fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 1-aza-10-oxa-7,9,13-trimethyl-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza- 10-oxa-7,9,13- trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-deca-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-deca-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-7-ethyl-16-(1-fluor-2-(2- methyl-4-thiazolyl)ethenyl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6- dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-10-ethyl-3-(1-fIuor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-7-ethyl-16- (1-fluoro-2- (2-methyl- 4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-10-ethyl-3- (1-fluorine-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(1 -fluor-2-(2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl ) ethenyl) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decan-5, 9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)- 7,9, 13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-deca-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-deca-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9,13-dimethyl-7-ethyl-16-(1 - ch!or-2-(2-methyl-4-thiazoIyl)ethenyl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-7-ethyl-16- (1 - ch! Or -2- (2-methyl-4-thiazoIyl) ethenyl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-10-ethyl-3-(1-chlor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1 ,3-trimethylen)-4, 13, 17-trioxabicyclo[14.1.Ojhepta- decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-10-ethyl-3- (1-chloro-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4, 13, 17-trioxabicyclo [14.1.Ojhepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy1 ,10-dioxa-9,13-dimethyl-16-(1-chlor-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy1, 10-dioxa-9,13-dimethyl-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-chlor-2-(2-methyl-(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-chloro-2- (2-methyl-

4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion4-thiazolyl) ethenyl) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5 , 9-dione

4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyl-4-thiazolyl)ethenyl)- 1-aza-10-oxa-7,9,13-trimethyl-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-deca-5,9-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza- 10-oxa-7,9,13- trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-deca-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-7-ethyl-16-(1-chlor-2-(2- methyl-4-thiazolyl)ethenyl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-7-ethyl-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-10-ethyl-3-(1-chlor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-10-ethyl-3- (1-chloro-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-chlor-2-(2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5.9- dion

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -5,5,9,13-tetramethyl-dione cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione

( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-( 1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -methyl-2-(2- pyridyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (prop-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cycIohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -methyl-2-(2-pyridyl)ethenyl)-7-(prop- 2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (prop- 2- en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1-yl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1-yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec- 13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13, 17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13, 17-dioxabicyclo [14.1.0] hepta-decane-5.9- dion

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -methyl-2-(2-methyl-4- thiazoIyl)ethenyl)-7-(prop-2-in-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazoIyl) ethenyl) -7- (prop-2-in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7,11 -Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop-2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(prop-2-in-1-yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-in-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7,11 -Dihydroxy-3-(1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop-2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(prop-2-in-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (prop-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyI)-10- (prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyI) -10- (prop-2-in -1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( prop-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-in-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop-2-in-1-yl) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en- 2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-in-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( prop-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-in-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(prop- 2-in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (prop- 2- in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-in-1-yl)-8,8,12,16-tetramethyI-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2-in -1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-in-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl ) ethenyl) -10- (prop-2-in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5.9- dion

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-in-1 -yl)-8,8-( 1 ,3-trimethylen)-4-aza-13, 17- dioxabicyc!o[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13, 17-dioxabicyc! O [14.1.0] hepta-decane-5, 9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-en-1-yi)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-en-1-yl) -5,5,9,13-tetramethyl-dione cyclohexadec-13-ene-2,6-

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(but-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazoI-4- yl)ethenyl)-10-(but-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (but-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazoI-4-yl) ethenyl) -10- (but -2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(but-2-en-1 -yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (but-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-3-(1 -methyI-2-(2-pyridyl)ethenyl)-10- (but-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13, 1 -trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2 -en-1 -yl) -8.8, 12, 16-tetramethyl-4, 13, 1 -trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( but-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1 S,3S(Z),7S, 10R,11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but-2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyioxazol-4- yl)ethenyl)-7-(but-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-methyl-2- (2-methyioxazol-4-yl) ethenyl) -7- ( but-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-en-1 -yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)etheny!)-7-(but-2- en-1 -yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-methyl-2- (2-pyridyl) etheny!) - 7- (but-2 - en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2-ene -1-yl) -8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazoIyl)ethenyl)-7-(but-2-en-1-yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-en-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazoIyl) ethenyl) -7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -10- (but-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5.9- dion

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-en-1-yl)-1-aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methy!-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methy! -2- (2-methyl-4-thiazolyl) ethenyl) -10- (but-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5.9 -dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-yn-1-yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but -2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(but-2-in-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (but-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyIoxazol-4- yl)ethenyl)-10-(but-2-in-1 -yl)-8,8, 12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but -2-in-1-yl) -8,8, 12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(but-2-in-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (but-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-in-1 -yl)-8,8, 12, 16-tetrametfιyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2-in -1 -yl) -8.8, 12, 16-tetrametfιyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13- en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( but-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but-2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(but-2-in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( but-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but-2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(but-2- in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (but-2- dione -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-in-1-yl)

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2 -in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(but-2-in-1-yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (but-2-yn-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-in-1 -yl)-8,8-(1 ,3-trimethylen)-4, 13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-in-1-yl) -8,8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-in-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5.9- dion

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (prop-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-5- benzoxazolyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -en-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-5-benzoxazolyl) -10- (prop-2 -en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(prop-2-en- 1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (prop-2-en-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(prop- 2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-en-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -en-1 -yl) -1 -aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop-2- en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (prop-2-in-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(prop- 2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(prop-2-in- 1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (prop-2-in-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(prop- 2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-in-1 -yl)-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (prop-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethyIen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop-2- in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-in-1-yI)-1-aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -in-1-yI) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-in-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13, 17- dioxabicydo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop-2- in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13, 17-dioxabicydo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (but-2-en-1-yl)-5,5,9,13-tetramethyl-cydohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -en-1-yl) -5,5,9,13-tetramethyl-cydohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(but-2-en- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (but-2-en-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9, 13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-en-1-yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4, 13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- en-1-yl) -8,8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Difιydroxy-9,13-dimethyl-16-(2-methyi-5- benzoxazolyl)-7-(but-2-en-1 -yl)-1-aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-en-1-yI)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-difydroxy-9,13-dimethyl-16- (2-methyi-5-benzoxazolyl) -7- (but-2 -en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- en-1-yI) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -in-1 -yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)- 10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 10- (but-2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane 5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(but-2-in-1 - yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (but-2-in-1 - yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-in-1 -yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-in-1 - yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (but-2-in-1-yl) -5,5 (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethylen)-4,13,17-trioxabicyclo[14.1.0]hepta- decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-in-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclot14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclot14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(prop-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1 -yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2 -en-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-5-benzothiazolyl) -10- (prop-2 -en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(prop-2- en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (prop-2-en-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-en-1 -yl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-en-1-yl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyI-5- benzothiazolyl)-7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (prop-2 -en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- en-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(2-methyl-5-benzothiazolyl)- 7-(prop-2-in-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2 -in-1 -yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-in-1-yI)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-in-1- yI) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(prop-2- in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-in-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (prop-2-in-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-in-1-yl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9, 13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2-in-1-yl) -5,5 (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (prop-2 -in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-in-1-yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(but-2-en-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (but-2 -en-1 -yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-en-1 -yl)-8,8, 12,16-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-en-1-yl) -8.8, 12.16-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(but-2-en- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (but-2-en-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-en-1 -yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethyIen)-4, 13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-en-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethyIen)cyclohexadec-13- en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- en-1-yl) -8,8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (but-2 -en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-en-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- en-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(but-2-in-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (but-2 -in-1 -yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,1 OR, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzothiazoly!)-10-(but- 2-in-1-yI)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 1 OR, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzothiazoly!) - 10- (but- 2-in- 1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazoIyl)-7-(but-2-in- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (2-methyl-5-benzothiazoIyl) -7- (but-2-in-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,1 OR, 11 S, 12R,16R)-7,11 -Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadeean-5,9-dion(1 S, 3S (Z), 7S, 1 OR, 11 S, 12R, 16R) -7.11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-in-1 -yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadeean-5,9-dione

(4S,7R,8S,9R, 13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9, 13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (but-2-in-1-yl) -5,5 (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-in-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (but-2 -in-1 -yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyi-2-(2-mefhyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-dione 5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6- (4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-dione 5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-

(1 S,3S(E),7S,10R,11 S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(E),7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-chIor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 , 10-dioxa-5,5,7,9-tetraamethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyI-cyclohexadec-13-ene-2,6-

(4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-dione 5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-

(1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S(E),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8.8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-7-ethyl-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-ethyl-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(E),7S,10R,11S,12S,16S)-16-Fluor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4, 13,17-trioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8, 12-trimethyl-4, 13,17-trioxabicyclo [14.1.Ojheptadecan-5,9-dione

(1R,3S(E),7S,10R,11S,12S,16R)-16-Fluor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4, 13, 17-trioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8, 12-trimethyl-4, 13, 17-trioxabicyclo [14.1.Ojheptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-7-allyl-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 , 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion (1S,3S(E) S,10R 1S,12S,16S)-16-Chlor-10-allyl-7,11-dihydrox -3-(1-mβthyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4, 13,17-trioxabicyclo[14.1. Ojheptadecan- 5,9-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-allyl-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (E) S, 10R 1S, 12S, 16S) -16-chloro-10-allyl-7,11-dihydrox -3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,12-trimethyl-4, 13,17-trioxabicyclo [14.1. Ojheptadecan 5,9-dione

(1 R,3S(E),7S, 10R, 11 S, 12S, 16R)-16-Chlor-10-aIlyl-7, 11 -dihydroxy-3-(1 -methy)-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4, 13,17-trioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-10-alyl-7, 11 -dihydroxy-3- (1-methy) -2- (2-methyl- 4-thiazolyl) ethenyl) -8,8,12-trimethyl-4, 13,17-trioxabicyclo [14.1. Ojheptadecan 5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-1 , 10-dioxa-5,5,7,9-tetraamethy!-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) -1, dion -cyclohexadec-13-en-2,6-10 dioxa-5,5,7,9-tetraamethy!

(1 S,3S(E),7S,1 OR, 11 S,12S, 16S)-16-Chlor-7,11 -dihydroxy-3-(1 -methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (E), 7S, 1 OR, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(E),7S,10R,11 S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxablcyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl ) -8,8,10,12-tetramethyl-4,13,17-trioxablcyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E, 16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -f luor-2-(2-methyI-4- thiazolyl)ethenyl)-1 , 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluorine-2- (2-methyl-4-thiazolyl) ethenyl) -1 , 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E, 16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -chlor-2-(2-methyl-4- thiazoIyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazoIyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6-

(1 S,3S(Z),7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion (1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 ,10-dioxa-7,9-dimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1, 10-dioxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10,12-dimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8,8-trimethylene-10,12-dimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 ,10-dioxa-7,9-dimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1, 10-dioxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7, 11 -dihydroxy-3-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11 -dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8-trimethylene-10,12-dimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8,8-trimethylene-10,12-dimethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- oxazolyl)ethenyl)-1 , 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) - 8,8, 10, 12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(1 -fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyI-cyclohexadec-13-en-2,6-dion(1 R, 3S (Z), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl ) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyI-cyclohexadec-13-ene-2,6-

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyI-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-7-ethyl-13-chlor-16-(1-chlor-2-(2-methyl-2- pyridyl)ethenyl)-1 ,10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-7-ethyl-13-chloro-16- (1-chloro-2- (2-methyl-2-pyridyl) ethenyl ) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyI-2-pyridyl)ethenyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2-pyridyl ) ethenyl) -8,8,12-trimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2- pyridyl) ethenyl) -8,8,12-trimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione

(4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S,7S, 10R, 11 S, 12S, 16S)-16-Fluor-7, 11 -dihydroxy-3-(2-methy!-5-benzothiazolyl)- 8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7, 11 -dihydroxy-3- (2-methy! -5-benzothiazolyl) - 8.8, 10, 12-tetramethyl -4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R.3S.7S, 10R, 1 S, 12S, 16R)-16-Fluor-7, 11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R.3S.7S, 10R, 1 S, 12S, 16R) -16-fluoro-7, 11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8, 10, 12-tetramethyl- 4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzothiazolyl)-1 , 10- dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1, 10- dioxa-5,5,7,9- tetraamethyl-Cyclohexadec-13-en-2,6-dione

(4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzothiazolyl)-1,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8, 10, 12-tetramethyl-4,13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dϊon(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1,10-dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dϊone

(1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-ethyl-13-chlor-16-(2-methyl-5-benzothiazoIyl)- 1 , 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-ethyl-13-chloro-16- (2-methyl-5-benzothiazoIyl) - 1, 10-dioxa-5,5, 9-trimethyl-cyclohexadec-13-en-dione 2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-trimethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S,7S,1 OR, 11 S,12S,16R)-16-Chlor-7,11 -dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 1 OR, 11 S, 12S, 16R) -16-chloro-7.11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8.8.12 tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-allyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1,10-dioxa-5,5,9-trimethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-allyl-13-chloro-16- (2-methyl-5-benzothiazolyl) - 1,10-dioxa-5,5, 9-trimethyl-cyclohexadec-13-en-dione 2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-trimethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12-trimethyl- 4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1,10-dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione

(4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1,10-dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S,7S,10R,11S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicycIo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4, 13,17-trioxabicycIo [14.1.0] heptadecane-5,9-dione

(1 R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4 , 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 ,10- dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1, 10- dioxa-5,5,7,9- tetraamethyl-Cyclohexadec-13-en-2,6-dione (4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicycIo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4, 13,17-trioxabicycIo [14.1.0] heptadecane-5,9-dione

(1 R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4 , 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione

(4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-Dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(E),7S, 10R, 11 S, 12S, 16S)-16-Fluor-7, 11 -dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion /(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione /

(1 R,3S(E),7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(1-methyl-2-(2-methyI-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1 R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.Ojheptadecan-5,9-dione

(4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-chlor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyI-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyI-cyclohexadec-13-ene-2,6-dione

(4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-Dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione

(1R,3S(E),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion (4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-7-ethyl-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione (4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-ethyl-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1-Aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(E),7S,10R,11S,12S,16S)-16-Fluor-10-ethyi-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4-aza-13, 17- dioxabicydo[14.1.0]heptadecan-5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8,12-trimethyl-4-aza-13, 17-dioxabicydo [14.1.0] heptadecane-5,9-dione

(1 R,3S(E),7S,10R,11S,12S,16R)-16-FIuor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17- dioxabicydo[14.1.0]heptadecan-5,9-dion(1 R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluor-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4- thiazolyl) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicydo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-7-allyl-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-101 -oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-allyl-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1-Aza-101-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dione

(1 S,3S(E),7S, 10R, 11 S, 12S, 16S)-16-Chlor-10-allyl-7, 11 -dihydroxy-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-chloro-10-allyl-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4 -thiazolyl) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(E),7S, 10R, 11 S, 12S, 16R)-16-Chlor-10-allyl-7, 11 -dihydroxy-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-10-allyl-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8, 12-trimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-chlor-16-(1 -methyl-2-(2-methyl-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-Dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(E),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7, 11 -dihydroxy-3-(1 -methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl ) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S(E),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-1-aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -1- aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione

(4S,7R,8S,9S, 13E, 16S(Z))-4,8-Dihydroxy-13-chior-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-1-aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -1- aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7, 11-dihydroxy-3-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.Ojheptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 -aza-10-oxa-7,9-dimethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1-aza-10-oxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7, 11 -dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10, 12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8-trimethylene-10, 12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S(Z),7S,10R,11S,12S,16R)-16 Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10, 12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16 chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10, 12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 -aza-10-oxa-7,9-dimethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1-aza-10-oxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10, 12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyI)ethenyl)-8,8-trimethylen-10,12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10, 12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyI) ethenyl) - 8,8-trimethylene-10,12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -f luor-2-(2-methyl-4- oxazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-f luor-2- (2-methyl-4-oxazolyl) ethenyl) -1 aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione

(1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione

(1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) - 8.8, 10, 12-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1. Ojheptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -f luor-2-(2-methyl-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-f luor-2- (2-methyl-2-pyridyl) ethenyl) -1 aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1 -fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl ) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-7-ethyl-13-chlor-16-(1 -chlor-2-(2-methyl-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-7-ethyl-13-chloro-16- (1-chloro-2- (2-methyl-2-pyridyl) ethenyl ) -1-Aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione

(1 S,3S(Z),7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1 -chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2 pyridyl) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecanoic

5,9-dion5,9-dione

(1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17-dioxabicyclo[ 14.1.OJheptadecan- 5,9-dion (4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetramethyl-cydohexadec-13-en-2,6-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2-pyridyl) ) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicyclo [14.1.OJheptadecan-5,9-dione (4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cydohexadec dione-13-en-2,6-

(4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6-

(1 S,3S,7S, 10R, 11 S, 12S, 16S)-16-FIuor-7, 11 -dihydroxy-3-(2-methyl-5-benzothiazolyi)- 8,8,10,12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-fluorine-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyi) - 8,8,10,12-tetramethyl- 4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4- aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetraamethyl cyclohexadec-dione-13-en-2,6-

(4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyI-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4- aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8, 10, 12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8, 10, 12-tetramethyl- 4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-ethyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-ethyl-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza-10-oxa-5, 5,9-trimethyl-cyclohexadec-13-en-dione 2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-trimethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-trimethyl- 4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-tetramethyl- 4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-7-allyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion (1 S,3S,7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-10-aIIyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-allyl-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza-10-oxa-5, 5,9-trimethyl-cyclohexadec-13-en-dione 2,6- (1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-aIIyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12- trimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12-tetramethyl- 4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1-aza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1-aza-10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6-

(4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1 -aza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1 -aza-10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyI)- 8,8,10,12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyI) - 8,8,10,12-tetramethyl-4- aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(1 R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4 aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

(4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 -aza-10- oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1 -aza-10-oxa-5,5,7, 9-tetraamethyl cyclohexadec-dione-13-en-2,6-

(4S,7R,8S,9S, 13Z, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 raza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1 raza-10-oxa-5,5,7,9 tetramethyl-Cyclohexadec dion-13-en-2,6-

(1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1 ,0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4- aza-13, 17-dioxabicyclo [14.1, 0] heptadecane-5,9-dione

(1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicycIo[14.1.0]heptadecan-5,9-dion (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-ChIor-7, 11 -dihydroxy-3-(2-methyI-5-benzothiazoIyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion (1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl- 4-aza-13,17-dioxabicycIo [14.1.0] heptadecane-5,9-dione (1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazoIyl) - 8,8,10,12-tetramethyl- 4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione

Die Darstellung der neuen Epothilon-Derivate, in denen R^ nicht Halogen oder Cyano ist, basiert auf der Verknüpfung dreier Teilfragmente A, B und C. Die Schnittstellen liegen wie in der allgemeinen Formel I' angedeutet.The representation of the new epothilone derivatives, in which R ^ is not halogen or cyano, is based on the linkage of three partial fragments A, B and C. The interfaces lie as indicated in the general formula I '.

ι\ι \

A bedeutet ein C-j-Cg-Fragment (Epothilon-Zählweise) der allgemeinen Formel A-1 oderA-2A represents a C-j-Cg fragment (epothilone counting) of the general formula A-1 or A-2

A"1 oder ^"^J worinA "1 or ^" ^ J wherein

R1 a', R1 b', R2a' und R2b' die bereits für R1 a, R1 b, R2a und R2b genanntenR 1 a ', R 1 b ', R2a 'and R 2b ' those already mentioned for R 1 a , R 1 b , R 2a and R 2b

Bedeutungen haben undHave meanings and

R19 CH2OR 9a, CH2-Hal, CHO, CO2R19b, COHal,R 19 CH 2 OR 9a , CH 2 -Hal, CHO, CO 2 R 19b , COHal,

R20 Wasserstoff, OR20a, Hai, OSO2R20b, R19a, R20a Wasserstoff, Sθ2-Alkyl, SO2-A17I, Sθ2-Aralkyl oder gemeinsam eineR 20 hydrogen, OR 20a , shark, OSO 2 R 20b , R 19a , R 20a hydrogen, Sθ2-alkyl, SO2-A17I, Sθ2-aralkyl or together one

-(CH2)0-Gruppe oder gemeinsam eine CR23aR23b-Gruppe,- (CH2) 0 group or together a CR 23a R 23b group,

R19b R20b Wasserstoff, C1 -C2o-Alkyl, Aryl, C-| -C2o-Aralkyl,R19b R 20b is hydrogen, C 1 -C 2 o-alkyl, aryl, C- | -C 2 o-aralkyl,

R28a, R23 gleich oder verschieden sind und Wasserstoff, C-j-C-j Q-Alkyl, Aryl,R 28a , R 23 are the same or different and are hydrogen, CjCj Q-alkyl, aryl,

C7-C20-Aralkyl, oder gemeinsam eine -(CH2)q-Gruppe, o 2 bis 4, q 3 bis 6,C7-C20-aralkyl, or together a - (CH2) q group, o 2 to 4, q 3 to 6,

R21 Wasserstoff,R 21 is hydrogen,

R22 Hydroxyl, oder R21 R22 gemeinsam ein Sauerstoffatom, oder eine C2-C-|Q-Alkylen-α,ω- dioxygruppe, die geradkettig oder verzweigt sein kann,R 22 hydroxyl, or R21 R22 together represent an oxygen atom, or a C2-C- | Q-alkylene-α, ω- dioxy group, which can be straight-chain or branched,

R21 J R22 jeweils eine C-j -C- Q-Alkoxygruppe, einschließlich aller Stereoisomeren sowie deren Gemische bedeuten sowie freie Hydroxylgruppen in R^9, R2υ und R22 verethert oder verestert, freie Carbonylgruppen in A-1 bzw A-2 ketalisiert, in einen Enolether überführt oder reduziert sowie freie Säuregruppen in A-1 bzw A-2 in deren Salze mit Basen überführt sein können.Etherified or R21 J R22 are each a C j -C-Q-alkoxy group, including all stereoisomers and mixtures thereof, as well as mean free hydroxyl groups in R ^ 9, R 22 and R 2υ esterified, free carbonyl groups in A-1 or A-2 ketalized , converted into an enol ether or reduced and free acid groups in A-1 or A-2 in their salts with bases can be converted.

B steht für ein C7-C^2-Fragment (Epothilon-Zählweise) der allgemeinen FormelB stands for a C7-C ^ 2 fragment (epothilone counting) of the general formula

worin R3a', R4' und R5' die bereits für R3a, R4 und R5 (außer R5'=Hal, CN) genannten Bedeutungen haben, und wherein R 3a ', R 4 ' and R 5 'have the meanings already given for R 3a , R 4 and R 5 (except R 5 ' = Hal, CN), and

V ein Sauerstoffatom, zwei Alkoxygruppen OR23, eine C2-C-|Q-Alkylen- ,ω- dioxygruppe, die geradkettig oder verzweigt sein kann oder H/OR24, W ein Sauerstoffatom, zwei Alkoxygruppen OR2^, eine C2-CiQ-Alkylen-α,ω- dioxygruppe, die geradkettig oder verzweigt sein kann oder H/OR2^,V is an oxygen atom, two alkoxy groups OR 23 , a C2-C- | Q-alkylene, ω-dioxy group, which can be straight-chain or branched or H / OR 24 , W is an oxygen atom, two alkoxy groups OR 2 ^, a C2-CiQ -Alkylene-α, ω- dioxy group, which can be straight-chain or branched or H / OR 2 ^,

R24, R ^ unabhängig voneinander Wasserstoff oder eine Schutzgruppe PG24,R 24 , R ^ independently of one another are hydrogen or a protective group PG 24 ,

R23, R ^ unabhängig voneinander C-ι-C20-Alkyl, bedeuten.R 23 , R ^ independently of one another are C 1 -C 20 -alkyl.

C steht für ein C13-C16~Fragment (Epothilon-Zählweise) der allgemeinen Formel C stands for a C13-C16 ~ fragment (epothilone counting) of the general formula

worinwherein

,12', 12 '

X'X '

G' eine Gruppe -' , ein bi-oder tricyclischer Arylrest,G 'is a group - ' , a bicyclic or tricyclic aryl radical,

R^2' die bereits in der allgemeinen Formel I für R^2 genannte Bedeutung hat und R7' ein Wasserstoffatom,R ^ 2 'has the meaning already given for R ^ 2 in the general formula I and R 7 ' is a hydrogen atom,

R27 Halogen, N3, NHR29, eine Hydroxygruppe, eine geschützte Hydroxygruppe O-R 27 halogen, N3, NHR 29 , a hydroxyl group, a protected hydroxyl group O-

PG27, eine geschützte Aminogruppe NR29PG27, eine C-j -C-j Q-PG 27 , a protected amino group NR 29 PG 27 , a Cj -C- j Q-

Alkylsulfonyloxygruppe, die gegebenenfalls perfluoriert sein kann, eine gegebenenfalls durch C-j-C4-Alkyl, Nitro, Chlor oder Brom substituierte Benzoyloxy-Gruppe, eine R2 Sθ2CH3-Gruppe, eine NR 9C(=O)CH3~Gruppe, eine CH2-C(=O)-CH3-Gruppe,Alkylsulfonyloxy group, which optionally can be perfluorinated, a substituted optionally substituted by C j-C4 alkyl, nitro, chlorine or bromine benzoyloxy group, an R 2 Sθ2CH3 group, a NR 9 C (= O) CH3 ~ group, a CH2 -C (= O) -CH 3 group,

R28 eine Hydroxygruppe, Halogen, eine geschützte Hydroxygruppe OPG28, einR 28 is a hydroxy group, halogen, a protected hydroxy group OPG 28

Phosphoniumhalogenidrest PPh3+Hal" (Ph = Phenyl; Hai = F, Cl, Br, I), einPhosphonium halide residue PPh3 + Hal " (Ph = phenyl; Hai = F, Cl, Br, I)

Phosphonatrest P(O)(OQ)2 (Q = C-j -C-j Q-Alkyl oder Phenyl) oder ein Phosphinoxidrest P(O)Ph2 (Ph = Phenyl),Phosphonate residue P (O) (OQ) 2 (Q = C-j -C-j Q-alkyl or phenyl) or a phosphine oxide residue P (O) Ph2 (Ph = phenyl),

X ein Sauerstoffatom, zwei Alkoxygruppen OR''3', eine C2-CiQ-Alkylen-α,co- dioxygruppe, die geradkettig oder verzweigt sein kann, H/OR^4' oder eine Gruppierung CR15 R16', wobei R13' für einen Cι-C20-Alkylrest,X is an oxygen atom, two alkoxy groups OR ' ' 3 ', a C2-CiQ-alkylene-α, co-dioxy group, which can be straight-chain or branched, H / OR ^ 4 ' or a group CR15 R16 ', where R 13 ' is a C 1 -C 20 -alkyl radical,

R^4' für Wasserstoff oder eine Schutzgruppe PG^4,R ^ 4 'for hydrogen or a protective group PG ^ 4 ,

R '5 , R16 gleich oder verschieden sind und für Wasserstoff, einen Cl-C20-Alkyl-,R ' 5 , R 16 are the same or different and are hydrogen, a Cl-C20-alkyl,

Aryl-, C7-C20-Aralkylrest stehen, bedeuten. Die Darstellung der neuen Epothilon-Derivate, in denen R^ gleich Halogen oder Cyano ist, basiert auf der Verknüpfung zweier Teilfragmente A und D. Die Schnittstellen liegen wie in der allgemeinen Formel I" angedeutet.Aryl, C7-C20 aralkyl radical are mean. The presentation of the new epothilone derivatives, in which R ^ is halogen or cyano, is based on the linkage of two partial fragments A and D. The interfaces lie as indicated in the general formula I ".

A entspricht hierbei dem bereits beschriebenen C-j-Cg-Fragment (Epothilon-Zählweise) der allgemeinen Formel A-1 oder A-2.A corresponds to the already described C-j-Cg fragment (epothilone counting) of the general formula A-1 or A-2.

D steht für ein C7-C15-Fragment (Epothilon-Zählweise) der allgemeinen FormelD stands for a C7-C15 fragment (epothilone counting) of the general formula

worin R5" für Halogen oder Cyano steht und R3a", R4", R27' und G" die bereits für R3a, R4, R27 und G genannten Bedeutungen haben.wherein R 5 "is halogen or cyano and R 3a ", R 4 ", R 27 'and G" have the meanings already given for R 3a , R 4 , R 27 and G.

Als Alkylgruppen Rla, R"1 , R2 , R2b, R3a, R4, R5, R9, R1 , R13, R13', R15, I Ö^As alkyl groups Rl a , R " 1, R 2 , R 2b , R 3a , R 4 , R5, R 9 , R1, R1 3 , R1 3 ', R15, I Ö ^

R16, R 6', R19 , R20b, R23, R25 sind gerad- oder verzweigtkettige Alkylgruppen mit 1-20 Kohlenstoffatomen zu betrachten, wie beispielsweise Methyl, Ethyl, Propyl, Isopropyl, Butyl, Isobutyl, tert.-Butyl, Pentyl, Isopentyl, Neopentyl, Heptyl, Hexyl, Decyl. Die Alkylgruppen R1 a, Rlb, R2a, R , R3a, R4, R5, R9, R12, R13 R13', R15? R15'; R16, R16', Rl b, R20 , R23, R23a, R23 , R25 können perfluoriert oder substituiert sein durch 1-5 Halogenatome, Hydroxygruppen, C^-C4-Alkoxygruppen, Cg-C^-R 16 , R 6 ', R 19 , R 20b , R 23 , R 25 are straight or branched chain alkyl groups with 1-20 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl , Pentyl, isopentyl, neopentyl, heptyl, hexyl, decyl. The alkyl groups R 1 a , Rl b , R 2a , R, R 3a , R 4 , R5, R 9 , R1 2 , R1 3 R1 3 ', R15 ? R15 '; R 16 , R16 ', Rl b , R 2 0, R 23 , R 23a , R 23 , R 2 5 can be perfluorinated or substituted be by 1-5 halogen atoms, hydroxyl groups, C ^ -C4-alkoxy groups, Cg-C ^ -

Arylgruppen (die durch 1-3 Halogenatome substituiert sein können).Aryl groups (which can be substituted by 1-3 halogen atoms).

Als Arylrest Rla, Rlb, R a, R b, R3a, R4, R5, R9, R12 R15, R15'? R16? R16'f R19bAs aryl radical Rl a , Rl b , R a , R b , R 3a , R 4 , R5, R 9 , R1 2 R15, R 15 ' ? R16 ? R 16 ' f R 19b

R 0D, R2 a, R b kommen substituierte und unsubstituierte carbocyclische oder heterocyclische Reste mit einem oder mehreren Heteroatomen wie z.B. Phenyl, Naphthyl, Furyl, Thienyl, Pyridyl, Pyrazolyl, Pyrimidinyl, Oxazolyl, Pyridazinyl, Pyrazinyl, Chinolyl, Thiazolyl, Benzothiazolyl, Benzoxazolyl, die einfach oder mehrfach substituiert sein können durch Halogen, OH, O-Alkyl, CO2H, Cθ2-Alkyl, -NH2, -NO2, -N3, -CN, C-j-R 0D , R 2 a , R b come substituted and unsubstituted carbocyclic or heterocyclic radicals with one or more heteroatoms such as phenyl, naphthyl, furyl, thienyl, pyridyl, pyrazolyl, pyrimidinyl, oxazolyl, pyridazinyl, pyrazinyl, quinolyl, thiazolyl, benzothiazolyl Benzoxazolyl, which can be mono- or polysubstituted by halogen, OH, O-alkyl, CO2H, CO 2 -alkyl, -NH2, -NO2, -N3, -CN, Cj-

C20-Alkyl, C-j-C20-Acyl, C-j-C20-Acyloxy-Gruppen, in Frage. Als bi- und tricyclische Arylreste G kommen substituierte und unsubstituierte carbocyclische oder heterocyclische Reste mit einem oder mehreren Heteroatomen wie z.B. Naphthyl, Anthryl, Benzothiazolyl, Benzoxazolyl, Benzimidazolyl, Chinolyl, Isochinolyl, Benzoxazinyl, Benzofuran, Indolyl, Indazolyl, Chinoxalinyl, Tetrahydroisochinolinyl, Tetrahydrochinolinyl, Thienopyridinyl, Pyridopyridinyl, Benzopyrazolyl, Benzotriazolyl, Dihydroindolyl, die einfach oder mehrfach substituiert sein können durch Halogen, OH, O-Alkyl, CO2H, Cθ2-Alkyl, -NH2, -NO2, -N3, -CN, C-j- C 20-alkyl, Cj-C20 acyl, Cj-C20-acyloxy groups, are suitable. The bi- and tricyclic aryl radicals G are substituted and unsubstituted carbocyclic or heterocyclic radicals having one or more heteroatoms, such as, for example, naphthyl, anthryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolyl, isoquinolyl, benzoxazinyl, benzofuran, tololrahoxylolinolinolinylinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinolinylinolinolinolinolinylinolinolinolinylinolinolinolinolinylolinolinylolinolinolinylolinolinolinolinolinolinolinylolinolinylolinolinylinolinolinylolinoxin Thienopyridinyl, pyridopyridinyl, benzopyrazolyl, benzotriazolyl, dihydroindolyl, which can be mono- or polysubstituted by halogen, OH, O-alkyl, CO2H, CO 2 -alkyl, -NH 2 , -NO2, -N 3 , -CN, Cj-

C20-Alkyl, C-j-C20-Acyl, C^-C20-Acyloxy-Gruppen, in Frage. C 20 -alkyl, C j -C20 acyl, C ^ C20-acyloxy groups, are suitable.

Die Aralkylgruppen in R a, R1 , R2a, R2 , R3a, R4, R5, R9, R12, R15, R15', R 6, R16'7 Rl9bι 20bj 23aj R23b können im Ring bis 14 C-Atome, bevorzugt 6 bis 10 und in der Alkylkette 1 bis 8, bevorzugt 1 bis 4 Atome enthalten. Als Aralkylreste kommen beispielweise in Betracht Benzyl, Phenylethyl, Naphthylmethyl, Naphthylethyl, Furylmethyl, Thienylethyl, Pyridylpropyl. Die Ringe können einfach oder mehrfach substituiert sein durch Halogen, OH, O-Alkyl, CO2H, Cθ2-Alkyl, -NO2, -N3, -CN, C-j-The aralkyl groups in R a , R 1 , R 2a , R 2 , R 3a , R 4 , R 5 , R 9 , R 12 , R 15 , R 15 ', R 6 , R16' 7 Rl9b ι 20b j 23a j R23b may contain up to 14 carbon atoms, preferably 6 to 10, and 1 to 8, preferably 1 to 4, atoms in the alkyl chain. Examples of suitable aralkyl radicals are benzyl, phenylethyl, naphthylmethyl, naphthylethyl, furylmethyl, thienylethyl, pyridylpropyl. The rings can be mono- or polysubstituted by halogen, OH, O-alkyl, CO2H, CO 2 -alkyl, -NO2, -N3, -CN, Cj-

C20-Alkyl, C-|-C20-Acyl, C-j-C20-Acyloxy-Gruppen. Die in R21 , R22 und X in der allgemeinen Formel I enthaltenen Alkoxygruppen sollen jeweils 1 bis 20 Kohlenstoffatome enthalten, wobei Methoxy-, Ethoxy- Propoxy- Isopropoxy- und t-Butyloxygruppen bevorzugt sind. Als Vertreter für die Schutzgruppen PG sind Alkyl- und/oder Aryl-substituiertes Silyl, C-j-C20 alkyl, C- | -C20 acyl, Cj-C20 acyloxy groups. The alkoxy groups contained in R 21 , R 22 and X in the general formula I are each intended to contain 1 to 20 carbon atoms, with methoxy, ethoxy-propoxy-isopropoxy and t-butyloxy groups being preferred. Representing the protective groups PG are alkyl- and / or aryl-substituted silyl, Cj-

C2o-Alkyl, C4-C7~Cycloalkyl, das im Ring zusätzlich ein Sauerstoffatom enthalten kann, Aryl, C7-C20-Aralkyl, C^-C20-Acyl sowie Aroyl zu nennen.C2o-alkyl, C4-C7 ~ cycloalkyl, which can additionally contain an oxygen atom in the ring, aryl, C7-C20-aralkyl, C ^ -C20-acyl and aroyl.

Als Alkyl-, Silyl- und Acylreste für die Schutzgruppen PG kommen die dem Fachmann bekannten Reste in Betracht. Bevorzugt sind aus den entsprechenden Alkyl- und Silylethem leicht abspaltbare Alkyl- bzw. Silylreste, wie beispielsweise der Methoxymethyl-, Methoxyethyl, Ethoxyethyl-, Tetrahydropyranyl-, Tetrahydrofuranyl-, Trimethylsilyl-, Triethylsilyl-, tert.-Butyldimethylsilyl-, tert.-Butyldiphenylsilyl-, Tribenzylsilyl-, Triisopropylsilyl-, Benzyl, para-Nitrobenzyl-, para-Methoxybenzyl-Rest sowie Alkylsulfonyl- und Arylsulfonylreste. Als Acylreste kommen z.B. Formyl, Acetyl, Propionyl, Isopropionyl, Pivalyl-, Butyryl oder Benzoyl, die mit Amino- und/oder Hydroxygruppen substituiert sein können, in Frage.The alkyl, silyl and acyl radicals for the protective groups PG are the radicals known to the person skilled in the art. Preferred are easily removable alkyl or silyl radicals from the corresponding alkyl and silyl ethers, such as, for example, methoxymethyl, methoxyethyl, ethoxyethyl, tetrahydropyranyl, tetrahydrofuranyl, Trimethylsilyl, triethylsilyl, tert.-butyldimethylsilyl, tert.-butyldiphenylsilyl, tribenzylsilyl, triisopropylsilyl, benzyl, para-nitrobenzyl, para-methoxybenzyl radicals and alkylsulfonyl and arylsulfonyl radicals. Examples of suitable acyl radicals are formyl, acetyl, propionyl, isopropionyl, pivalyl, butyryl or benzoyl, which can be substituted with amino and / or hydroxyl groups.

Als Aminoschutzgruppen kommen die dem Fachmann bekannten Reste in Betracht. Beispielsweise genannt seien die Alloc-, Boc-, Z-, Benzyl, f-Moc-, Troc-, Stabase- oder Benzostabase-Gruppe.The residues known to the person skilled in the art are suitable as amino protective groups. Examples include the Alloc, Boc, Z, benzyl, f-Moc, Troc, stabase or benzostabase group.

Die Acylgruppen PG können 1 bis 20 Kohlenstoffatome enthalten, wobei Formyl-, Acetyl-, Propionyl-, Isopropionyl und Pivalylgruppen bevorzugt sind.The acyl groups PG can contain 1 to 20 carbon atoms, formyl, acetyl, propionyl, isopropionyl and pivalyl groups being preferred.

Der Index m in der aus R^a und R""3 gebildeten Alkylengruppe steht vorzugsweise für 1, 2, 3 oder 4.The index m in the alkylene group formed from R ^ a and R " " 3 is preferably 1, 2, 3 or 4.

Die für R21, R22, V, W und X mögliche C2-C-jQ-Alkylen- ,ω-dioxygruppe ist vorzugsweise eine Ethylenketal- oder Neopentylketalgruppe. The C2-C-JQ-alkylene, ω-dioxy group which is possible for R 2 1, R 22 , V, W and X is preferably an ethylene ketal or neopentyl ketal group.

Darstellung der Teilfragmente A:Representation of partial fragments A:

Die Teilfragmente (Synthesebausteine) der allgemeinen Formel A-1 und A-2 lassen sich wie in DE 197 51 200.3, DE 199 07 480.1 , DE 199 21 0861.1 und WO 99/07692 herstellen.The partial fragments (synthesis building blocks) of the general formulas A-1 and A-2 can be prepared as in DE 197 51 200.3, DE 199 07 480.1, DE 199 21 0861.1 and WO 99/07692.

Darstellung der Teilfragmente B:Representation of partial fragments B:

Schema 1Scheme 1

B-IV B-V B B-IV BV B

Die Darstellung von Fragmenten des Typs B, in denen R3a', R ',R5', V und W alle bereits genannten Bedeutungen haben können, ist in Schema 1 gezeigt. Die Synthese kann sowohl ausgehend von enantiomerenreien Verbindungen B-l als auch racemisch durchgeführt werden.The illustration of fragments of type B, in which R 3a ', R', R5 ', V and W can have all the meanings already mentioned, is shown in Scheme 1. The synthesis can be carried out either from enantiomerically free compounds B1 or racemically.

Schritt a (B-l => B-Il): Verbindungen des Typs B-l sind z.T. käuflich. In diesen Fällen wird nach dem Fachmann bekannten Verfahren die primäre Alkoholfunktion selektiv geschützt.Step a (B-l => B-Il): Compounds of the type B-l are partly sale. In these cases, the primary alcohol function is selectively protected by methods known to those skilled in the art.

Prinzipiell kommen alle z.B. für PG5 genannten Schutzgruppen in Frage. Besonders bevorzugt ist z.B. die Tetrahydropyranylschutzgruppe. Für nicht käufliche Verbindungen des Typs B-I wird der Rest R4' nach den dem Fachmann bekannten Verfahren, z. B. durch nukleophile Substitution an entsprechende Aldehyde hergestellt.In principle, all protective groups mentioned, for example, for PG 5 can be used. For example, the tetrahydropyranyl protecting group is particularly preferred. For connections not for sale of type BI, the radical R 4 'according to the methods known to those skilled in the art, for. B. prepared by nucleophilic substitution to corresponding aldehydes.

Schritt b (B-Il= B-Ill): Durch 1,4-Addition von Verbindungen des Typs B-Il an α,ß-ungesättigte Carbonylverbindungen werden Verbindungen des Typs B-Ill erhalten. R^'a kann hierbei alle bereits für R^' genannten Bedeutungen haben und zusätzlich gleich O-Alkyl sein.Step b (B-Il = B-Ill): 1,4-addition of compounds of the type B-Il to α, β-unsaturated carbonyl compounds gives compounds of the type B-Ill. R ^ ' a can have all the meanings already mentioned for R ^' and can also be O-alkyl.

Schritt c (B-III^ B-IV): Für Verbindungen des Typs B-Ill, in denen R5'a die Bedeutung O-Alkyl hat, kann zum Aldehyd B-IV reduziert werden. Die Überführung in den Aldehyd erfolgt entweder direkt z.B. durch Reduktion mit Diisobutylaluminiumhydrid bei tiefen Temperaturen (unter -40°C) oder aber zweistufig durch Reduktion zum Alkohol und anschließende Oxidation. Hierfür kommen dem Fachmann bekannte Verfahren zur Anwendung. Für die Reduktion werden z.B. komplexe Hydride wie Lithiumaluminiumhydrid verwendet. Die Oxidation kann z.B. nach den zur Darstellung von A-Ill beschriebenen Verfahren erfolgen.Step c (B-III ^ B-IV): For compounds of the type B-III in which R 5 ' a is O-alkyl, the aldehyde B-IV can be reduced. The conversion into the aldehyde is carried out either directly, for example by reduction with diisobutylaluminum hydride at low temperatures (below -40 ° C.) or in two stages by reduction to alcohol and subsequent oxidation. Methods known to those skilled in the art are used for this. For example, complex hydrides such as lithium aluminum hydride are used for the reduction. The oxidation can take place, for example, according to the methods described for the illustration of A-III.

Schritt d (B-IV=» B-V): Durch nucleophile Addition von metallorganischen Verbindungen der theoretischen Formel M-R^', worin M für Indium, ein Alkalimetall, vorzugsweise Lithium oder ein zweiwertiges Metall MX, worin X ein Halogen repräsentiert und der Rest R ' die oben genannten Bedeutungen aufweist. Als zweiwertiges Metall ist bevorzugt Magnesium und Zink, als Halogen X ist bevorzugt Chlor, Brom und lod.Step d (B-IV = »BV): by nucleophilic addition of organometallic compounds of the theoretical formula MR ^ ', in which M is indium, an alkali metal, preferably lithium or a divalent metal MX, in which X represents a halogen and the rest R' has the meanings given above. Magnesium and zinc are preferred as divalent metal, and chlorine, bromine and iodine are preferred as halogen X.

Schritt e (B-Ill^ B-V):Step e (B-Ill ^ B-V):

Für Verbindungen, in denen R5'a für O-Alkyl steht, kann man auch direkt durch nucleophile Addition zu Verbindungen des Typs B-V gelangen. Hierfür kommen dem Fachmann bekannte Methoden zum Einsatz, wie z.B. die Verwendung von Dialkylkupferlithium-Verbindungen.For compounds in which R 5 ' a is O-alkyl, compounds of the type BV can also be obtained directly by nucleophilic addition. Methods known to those skilled in the art are used for this, such as the use of dialkyl copper lithium compounds.

Schritt f (B-V=> B):Step f (B-V => B):

Die Überführung von B-V in Teilfragmente der allgemeinen Formel B erfolgt analog zu den in WO 99/07692 beschriebenen Verfahren. Schritt g (B-Ill=> B):BV is converted into partial fragments of the general formula B analogously to the processes described in WO 99/07692. Step g (B-Ill => B):

Für Verbindungen, in denen R5'a nicht O-Alkyl bedeutet, kann Verbindung B- ebenfalls analog WO 99/07692 in Teilfragmente des Typs B überführt werden. For compounds in which R 5 ' a is not O-alkyl, compound B- can also be converted into partial fragments of type B analogously to WO 99/07692.

Darstellung der Teilfragmente C:Representation of the partial fragments C:

Die Teilfragmente (Synthesebausteine) der allgemeinen Formel C lassen sich wie in DE 197 51 200.3, DE 199 07480.1 und WO 99/07692 hersteilen.The partial fragments (synthesis building blocks) of the general formula C can be prepared as in DE 197 51 200.3, DE 199 07480.1 and WO 99/07692.

Darstellung der Teilfragmente ABC und deren Zyklisierung zu I erfolgt ebenfalls analog wie in WO 99/07692 für zahlreiche Epothilon-Derivate beschrieben ist,Representation of the partial fragments ABC and their cyclization to I is likewise carried out analogously as described in WO 99/07692 for numerous epothilone derivatives,

WO 99/07692 belegt schon die allgemeine Anwendbarkeit des nachfolgend für die erfindungsgemäßen Verbindungen beschriebenen Syntheseprinzips. Außerdem gehen aus WO 99/07692 zahlreiche Synthesebausteine der allgemeinen Formeln A, B und C hervor, mit denen sich weitere der hier beanspruchten Verbindungen der allgemeinen Formel I erhalten lassen. Synthesebausteine der allgemeinen Formel C, in denen alsWO 99/07692 already proves the general applicability of the synthetic principle described below for the compounds according to the invention. In addition, WO 99/07692 shows numerous synthesis building blocks of the general formulas A, B and C, with which further compounds of the general formula I claimed here can be obtained. Synthesis building blocks of the general formula C, in which as

R^ ein Halogenatom, insbesondere ein Fluor-, Chlor- oder Bromatom, vorhanden ist, sind Gegenstand der DE 199 07 480.1 und PCT/EP00/01333. R ^ is a halogen atom, in particular a fluorine, chlorine or bromine atom, are the subject of DE 199 07 480.1 and PCT / EP00 / 01333.

Darstellung der Teilfragmente D:Representation of the partial fragments D:

Die Synthese der Teilfragmente D ist im folgenden Schema 2 ausgehend von den Aldehyden der allgemeinen Formel D-l beschrieben.The synthesis of the partial fragments D is described in the following scheme 2 starting from the aldehydes of the general formula D-1.

Schema 2Scheme 2

D-IlldD-Hid

B-IlB-Il

Schritt a (D-l → D-IV): Step a (Dl → D-IV):

Die Verbindung D-l wird mit dem Enolat einer Carbonylverbindung der allgemeinenThe compound D-1 with the enolate of a carbonyl compound of the general

Formel D-Il, worin X ein Wasserstoff und chG2 eine chirale Hilfsgruppe sein kann, nach den, dem Fachmann bekannten Methoden alkyliert. Das Enolat wird durch Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Lithiumhexamethyldisilazan bei niedrigen Temperaturen hergestellt. Eine weitere Möglichkeit besteht in einer ArtFormula D-Il, in which X can be a hydrogen and chG 2 can be a chiral auxiliary group, alkylated by the methods known to the person skilled in the art. The enolate is produced by the action of strong bases such as lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures. Another possibility is a kind

Reformatzsky-Reaktion bei der die Verbindung der allgemeinen Formel D-Il mit X = Halogen, vorzugsweise Chlor oder Brom, mit CrCl2 in ein metallorganisches Reagenz überführt wird, welches dann mit dem Aldehyd D-l zu D-IV reagiert. Als chirale Hilfsgruppe chG2-H (D-HI) eignen sich chirale, optisch rein herstellbare und wohlfeileReformatzsky reaction in which the compound of the general formula D-II with X = halogen, preferably chlorine or bromine, is converted with CrCl2 into an organometallic reagent which then reacts with the aldehyde Dl to give D-IV. As a chiral auxiliary group chG 2 -H (D-HI), chiral, optically purely producible and inexpensive are suitable

Alkohole wie z.B. Pulegol, 2-Phenylcyclohexanol, 2-Hydroxy-1,2,2-triphenylethanol, 8-Alcohols such as Pulegol, 2-phenylcyclohexanol, 2-hydroxy-1,2,2-triphenylethanol, 8-

Phenylmenthol oder optisch rein herstellbare und wohlfeile, reaktive NH-GruppenPhenylmenthol or inexpensive, inexpensive, reactive NH groups

/ enthaltende Verbindungen wie z.B. Amine, Aminosäuren, Lactame oder Oxazolidinone./ containing compounds such as Amines, amino acids, lactams or oxazolidinones.

Bevorzugt sind Oxazolidinone, besonders bevorzugt die Verbindungen der Formeln D- lila bis D-Illd. Durch die Wahl des jeweiligen Antipoden wird die absolute Stereochemie am α-Carbonylkohlenstoff der Verbindung der allgemeinen Formel D-IV festgelegt. Auf diesem Wege lassen sich die Verbindungen der allgemeinen Formeln D-IV bis D-XV bzw. deren jeweilige Enantiomere ent-D-IV bis ent-D-XV enantiomerenrein erhalten. Wird als chG2-H (D-Ill) ein achiraler Alkohol wie z.B. Ethanol eingesetzt; so erhält man die racemischen Verbindungen rac-D-IV bis rac-D-XV.Oxazolidinones are preferred, particularly preferably the compounds of the formulas D-lilac to D-Illd. The choice of the respective antipode determines the absolute stereochemistry of the α-carbonyl carbon of the compound of the general formula D-IV. In this way, the compounds of the general formulas D-IV to D-XV or their respective enantiomers ent-D-IV to ent-D-XV can be obtained enantiomerically pure. If an achiral alcohol such as ethanol is used as chG 2 -H (D-Ill); this gives the racemic compounds rac-D-IV to rac-D-XV.

Anschließend wird die freie Hydroxylgruppe in B-IV nach den, dem Fachmann bekannten Methoden geschützt. Als Schutzgruppen PG15 kommen die, dem Fachmann bekannten Schutzgruppen, wie sie schon vorstehend für PG5 (A-l → A-Il) genannt wurden, in Frage. Bevorzugt sind Silizium haltige Schutzgruppen, die unter sauren Reaktionsbedingungen oder Anwendung von Fluorid gespalten werden können, wie z.B. der Trimethylsilyl-, Triethylsilyl-, tert.-Butyldimethylsilyl-, tert.-Butyldiphenylsilyl-, Tribenzylsilyl-, Triisopropylsilyl-Rest. Besonders bevorzugt ist der tert.-Butyldiphenylsilyl- und tert.-Butyldimethylsilyl Rest.The free hydroxyl group in B-IV is then protected by the methods known to the person skilled in the art. Protecting groups PG15 are the protective groups known to the person skilled in the art, as have already been mentioned above for PG5 (A-1 → A-II). Protective groups containing silicon which can be cleaved under acidic reaction conditions or using fluoride, such as e.g. the trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, tribenzylsilyl, triisopropylsilyl radical. The tert-butyldiphenylsilyl and tert-butyldimethylsilyl radical is particularly preferred.

Schritt b (D-IV → D-V):Step b (D-IV → D-V):

Repräsentiert die Gruppe chG2 eine der unter Schritt a erwähnten chiralen Hilfsgruppen, so wird diese durch Umesterung von D-IV in einen Alkylester der allgemeinen Formel D-V wiedergewonnen. Die Umesterung erfolgt nach den, dem Fachmann bekannten Methoden. Bevorzugt ist die Umesterung mit einfachen Alkoholen wie z.B. Methanol oder Ethanol in Gegenwart entsprechender Titan(IV)alkoholate. Schritt c (DN → D-VI):If the group chG 2 represents one of the chiral auxiliary groups mentioned under step a, this is recovered by transesterification of D-IV into an alkyl ester of the general formula DV. The transesterification takes place according to the methods known to the person skilled in the art. Transesterification with simple alcohols such as methanol or ethanol in the presence of corresponding titanium (IV) alcoholates is preferred. Step c (DN → D-VI):

Der Ester in D-V wird zum Alkohol D-Vl reduziert. Als Reduktionsmittel eignen sich die, dem Fachmann bekannten Reduktionsmittel wie z.B. Aluminiumhydride wie z.B. Lithiumaluminiumhydrid oder Diisobutylaluminium-hydrid. Die Reaktion erfolgt in einem inerten Lösungsmittel wie z.B. Diethylether, Tetrahydrofuran, Toluol.The ester in D-V is reduced to alcohol D-Vl. Suitable reducing agents are the reducing agents known to the person skilled in the art, e.g. Aluminum hydrides such as Lithium aluminum hydride or diisobutyl aluminum hydride. The reaction takes place in an inert solvent such as e.g. Diethyl ether, tetrahydrofuran, toluene.

Schritt c* (D-IV → D-Vl):Step c * (D-IV → D-Vl):

Alternativ zu den Schritten b) und c) kann die Carbonylgruppe in D-IV nach den unter Schritt c) genannten Bedingungen direkt zu den Alkoholen der allgemeinen Formel D-Vl reduziert werden. Auch hier kann die chirale Hilfskomponente chG -H wiedergewonnen werden.As an alternative to steps b) and c), the carbonyl group in D-IV can be reduced directly to the alcohols of the general formula D-VI under the conditions mentioned under step c). The chiral auxiliary component chG -H can also be recovered here.

Schritt d (D-VI → D-Vl I):Step d (D-VI → D-VI I):

Die Oxidation des primären Alkohols in D-Vl zum Aldehyd der allgemeinen Formel D-Vll erfolgt nach den, dem Fachmann bekannten Verfahren. Beispielsweise genannt sei dieThe oxidation of the primary alcohol in D-VI to the aldehyde of the general formula D-VIII takes place according to the methods known to the person skilled in the art. For example, the

Oxidation mit Pyridiniumchlorochro at, Pyridiniumdichromat, Chromtrioxid-Pyridin-Oxidation with pyridinium chlorochroate, pyridinium dichromate, chromium trioxide pyridine

Komplex, die Oxidation nach Swern oder verwandter Methoden z.B. unter Verwendung von Sθ3-Pyridin-Komplex oder Oxalylchlorid in Dimethylsulfoxid, die Verwendung desComplex, oxidation according to Swern or related methods e.g. using Sθ3-pyridine complex or oxalyl chloride in dimethyl sulfoxide, the use of the

Dess-Martin-Periodinans, die Verwendung von Stickstoffoxiden wie z.B. N-Methyl- morpholino-N-oxid in Gegenwart geeigneter Katalysatoren wie z.B.Dess-Martin periodinans, the use of nitrogen oxides such as N-methylmorpholino-N-oxide in the presence of suitable catalysts such as e.g.

Tetrapropylammoniumperruthenat in inerten Lösungsmitteln. Bevorzugt ist die Oxidation nach Swern, Sθ3-Pyridin-Komplex sowie mit N-Methyl-morpholino-N-oxid unter Verwendung von Tetrapropylammoniumperruthenat.Tetrapropylammonium perruthenate in inert solvents. Oxidation according to Swern, Sθ3-pyridine complex and with N-methyl-morpholino-N-oxide using tetrapropylammonium perruthenate is preferred.

Schritt e (D-Vll - D-Vlll):Step e (D-Vll - D-Vlll):

Die ungesättigten Ester der allgemeinen Formel D-Vlll werden durch die dem Fachmann bekannten Verfahren hergestellt. Hierzu eignen sich Methoden wie z.B. die Wittig- oder Wittig/Horner-Reaktion, oder auch die Peterson-Olefinierung. Bevorzugt ist die Wittig/Horner-Reaktion unter Verwendung von Phosphonaten des Typs AlkylOOC- CHR5"-P(O)(OAIkyl')2 wobei Alkyl und Alkyl' gleich oder verschieden sein können und vorzugsweise Methyl, Ethyl, i-Propyl oder Trifluorethyl bedeuten und R5' die bereits genannte Bedeutung hat, mit Basen wie z.B. Kaliumcarbonat, Natriumhydrid, n- Butyllithium, Kalium-tert.-butanolat, Natriumethanolat, Lithiumhexamethyldisilazan, Natriumhexamethyldisilazan, Kaliumhexamethyldisilazan und gegebenenfalls mit Zusätzen von beispielsweise Kronenethern, DMPU oder HMPA, in Lösungsmittel wie Methanol, Tetrahydrofuran, Dimethylformamid, Diethylether, bevorzugt ist die Kombination von Kaliumcarbonat in Methanol, Natriumhydrid in Dimethylformamid oder Tetrahydrofuran und Kaliumhexamethyldisilazan mit 18-Krone-6 in Tetrahydrofuran. Die erhaltenen E/Z-Diastereomeren können beispielsweise auf dieser oder der nächsten Stufe getrennt werden und können einzeln für sich in die entsprechenden E- bzw. Z-Olefinendprodukte überführt werden. In dem Formelschema ist der übersichtlichkeithalber nur die E-Form dargestellt. Alle folgende Schritte gelten jedoch auch für das entsprechende Z-Isomer.The unsaturated esters of the general formula D-VIII are produced by the processes known to the person skilled in the art. Methods such as the Wittig or Wittig / Horner reaction or the Peterson olefination are suitable for this. The Wittig / Horner reaction is preferred using phosphonates of the alkylOOC-CHR5 "-P (O) (OAIkyl ') 2 type, where alkyl and alkyl' may be the same or different and are preferably methyl, ethyl, i-propyl or trifluoroethyl and R5 'has the meaning already mentioned, with bases such as, for example, potassium carbonate, sodium hydride, n-butyllithium, potassium tert-butanolate, sodium ethanolate, lithium hexamethyldisilazane, sodium hexamethyldisilazane, potassium hexamethyldisilazane and, if appropriate, with additions of, for example, crown ethers, DMPU or HMPA, in solvents such as Methanol, tetrahydrofuran, dimethylformamide, diethyl ether, preference is given to the combination of potassium carbonate in methanol, sodium hydride in dimethylformamide or tetrahydrofuran and potassium hexamethyldisilazane with 18-crown-6 in tetrahydrofuran. The E / Z diastereomers obtained can, for example, be separated at this or the next stage and can be converted individually into the corresponding E or Z olefin end products. For the sake of clarity, only the E-form is shown in the formula diagram. However, all of the following steps also apply to the corresponding Z isomer.

Schritt f (D-Vlll → D-IX):Step f (D-VIII → D-IX):

Verbindungen des Typs D-Vlll werden durch d-Verlängerung in Verbindungen desCompounds of the type D-VIII are converted into compounds of the by d-extension

Typs D-IX überführt. Diese C Verlängerung erfolgt nach mehrstufigen Verfahren. Beispielsweise kann die Esterfunktion in D-Vlll zu einem primären Alkohol reduziert werden. Als Reduktionsmittel eignen sich die, dem Fachmann bekannten Reduktionsmittel wie z.B. Aluminiumhydride wie z.B. Lithiumaluminiumhydrid oder Diisobutylaluminium-hydrid. Die Reaktion erfolgt in einem inerten Lösungsmittel wie z.B. Diethylether, Tetrahydrofuran, Toluol. Der primäre Alkohol kann dann in eine Fluchtgruppe, wie z.B. ein Halogenid oder eine OSO2-Alkyl-, O-SO2-Aryl- oder OSÖ2- Aralkylgruppe überführt werden. Die Einführung des späteren C-14 kann dann z.B. mittels Substitution durch Cyanid unter Verwendung von NaCN oder KCN erfolgen. Das gebildete Nitril wird anschließend durch Reduktion mit z.B. Diisobutylaluminium-hydrid und saure Spaltung des primär gebildeten Imins in einen Aldehyd überführt, der dann z.B. mit Lithiumaluminiumhydrid, Natriumborhydrid oder Diisobutylaluminium-hydrid in den primären Alkohol des Typs D-IX überführt wird.Type D-IX transferred. This C extension is based on a multi-stage process. For example, the ester function in D-VIII can be reduced to a primary alcohol. Suitable reducing agents are the reducing agents known to the person skilled in the art, such as, for example, aluminum hydrides such as, for example, lithium aluminum hydride or diisobutyl aluminum hydride. The reaction takes place in an inert solvent such as diethyl ether, tetrahydrofuran, toluene. The primary alcohol can then be converted into a leaving group, such as a halide or an OSO 2 alkyl, O-SO 2 aryl or OSÖ 2 aralkyl group. The later C-14 can then be introduced, for example, by substitution with cyanide using NaCN or KCN. The nitrile formed is then converted into an aldehyde by reduction with, for example, diisobutylaluminum hydride and acid cleavage of the primarily formed imine, which is then converted into the primary alcohol of type D-IX, for example with lithiumaluminum hydride, sodium borohydride or diisobutylaluminum hydride.

Schritt g (D-IX + B-Il→ D-X):Step g (D-IX + B-Il → D-X):

Die Darstellung von Verbindungen des Typs D-X erfolgt dann durch Verknüpfung von D-IX mit bereits beschriebenen Verbindungen des Typs B-Il. Diese läßt sich z.B. unterCompounds of type D-X are then represented by linking D-IX with previously described compounds of type B-II. This can e.g. under

Verwendung von Triphenylphosphin und Azodiestem wie beispielsweiseUse of triphenylphosphine and azodiesters such as

Azodicarbonsäurediethylester durchführen. Alternativ hierzu kann auch eine der beiden Hydroxyfunktionen (in Baustein D-IX oder B-Il) in ein Halogenid oder eine OSθ2Alkyl,Carry out diethyl azodicarboxylate. Alternatively, one of the two hydroxyl functions (in building block D-IX or B-II) can be converted into a halide or an OSO 2 alkyl,

OSθ2Aryl oder OSθ2Araikyl-Gruppe überführt werden. Vorzugsweise wird die Fluchtgruppe an der primären Alkoholfunktion in Baustein D-IX gebildet. Zur Verknüpfung beider Bausteine wird dann die freie Hydroxylgruppe in dem jeweils anderen Baustein, vorzugsweise B-Il, mit geeigneten Basen wie beispielsweise Natriumhydrid, n-Buthyllithium, 4-Dimethylaminopyridin, Hünig-Base,OSθ2Aryl or OSθ2Araikyl group are transferred. The escape group is preferably formed on the primary alcohol function in building block D-IX. To link both building blocks, the free hydroxyl group in the other building block, preferably B-II, is then mixed with suitable bases such as, for example, sodium hydride, n-butyllithium, 4-dimethylaminopyridine, Hünig base,

Alkylihexamethyldisilazanen deprotoniert und durch nucleophile Substitution in Verbindungen des Typs D-X überführt.Deprotonated alkylihexamethyldisilazanes and converted into compounds of type D-X by nucleophilic substitution.

Schritt h (D-X→ D-Xl): Für den Fall, daß R27'= OPG27 ist wird die Schutzgruppe PG7 nun nach den, dem Fachmann bekannten Verfahren gespalten. Handelt es sich um eine sauer spaltbare Schutzgruppe, so eignen sich für die Spaltung verdünnte Mineralsäuren in wässrig- alkoholischen Lösungen, die Verwendung von katalytischen Mengen Säuren wie z.B. para-Toluolsulfonsäure, para-Toluolsulfonsäure-pyridiniumsalz, Camphersulfonsäure in alkoholischen Lösungen, vorzugsweise in Ethanol oder Isopropanol.Step h (DX → D-Xl): In the event that R 27 '= OPG 27 , the protective group PG 7 is now split according to the methods known to the person skilled in the art. If it is an acidic cleavable protective group, dilute mineral acids in aqueous alcoholic solutions are suitable, the use of catalytic amounts of acids such as para-toluenesulfonic acid, para-toluenesulfonic acid pyridinium salt, camphorsulfonic acid in alcoholic solutions, preferably in ethanol or isopropanol.

Für den Fall, daß A in den Verbindungen der Formel I eine NR^7-Gruppe ist, wird vor der Abspaltung der Schutzgruppe PG7 zuerst die Schutzgruppe PG27 selektiv nach den, dem Fachmann bekannten Methoden gespalten (s. hierzu auch weiter oben). Den so erhaltenen sekundären Alkohol überführt man mit einem Sulfonylchlorid oder einemIn the event that A in the compounds of the formula I is an NR ^ 7 group, before the protective group PG 7 is split off, the protective group PG 27 is first split selectively by the methods known to the person skilled in the art (see also above) , The secondary alcohol thus obtained is converted with a sulfonyl chloride or a

Sulfonsäureanhydrid in ein Sulfonat und gegebenfalls anschließend in einer Finkelstein-Sulfonic anhydride in a sulfonate and, if appropriate, subsequently in a Finkelstein

Reaktion mit einem Alkalibromid oder -chlorid, oder durch Reaktion des sekundären Alkohols mit CBr4 in Gegenwart von Triphenylphosphin bzw. Bis(diphenylphosphinoethan) in ein sekundäres Halogenid. Die so erhaltenenReaction with an alkali bromide or chloride, or by reaction of the secondary alcohol with CBr4 in the presence of triphenylphosphine or bis (diphenylphosphinoethane) in a secondary halide. The so obtained

Halogenide oder Sulfonate können dann durch eine nucleophile Substitution mit z. B.Halides or sulfonates can then be replaced by a nucleophilic substitution with e.g. B.

Natriumazid in einem neutralen polaren Lösungsmittel wie beispielsweise Dimethylformamid oder Dimethylsulfoxid in ein entsprechendes Azid (L' = N3) überführt werden. Danach würde sich die oben beschriebene Spaltung der Schutzgruppe PG7 anschließen.Sodium azide in a neutral polar solvent such as dimethylformamide or dimethyl sulfoxide can be converted into a corresponding azide (L '= N3). This would be followed by the splitting of the PG 7 protective group described above.

Schritt i (D-Xl → D):Step i (D-Xl → D):

Die Oxidation des primären Alkohols in D-Xl zum entsprechenden Aldehyd erfolgt nach den, dem Fachmann bekannten Verfahren. Beispielsweise genannt sei die Oxidation mit Pyridiniumchlorochromat, Pyridiniumdichromat, Chromtrioxid-Pyridin-Komplex, die Oxidation nach Swern oder verwandter Methoden z.B. unter Verwendung von SO3-The oxidation of the primary alcohol in D-Xl to the corresponding aldehyde takes place according to the methods known to the person skilled in the art. Examples include oxidation with pyridinium chlorochromate, pyridinium dichromate, chromium trioxide-pyridine complex, oxidation according to Swern or related methods, e.g. using SO3-

Pyridin-Komplex oder von Oxalylchlorid in Dimethylsulfoxid, die Verwendung des Dess- Martin-Periodinans, die Verwendung von Stickstoffoxiden wie z.B. N-Methyl- morpholino-N-oxid in Gegenwart geeigneter Katalysatoren wie z.B. Tetrapropylammoniumperruthenat in inerten Lösungsmitteln. Bevorzugt ist die Oxidation nach Swern sowie mit N-Methyl-morpholino-N-oxid unter Verwendung von Tetrapropylammoniumperruthenat.Pyridine complex or of oxalyl chloride in dimethyl sulfoxide, the use of Dess-Martin periodinane, the use of nitrogen oxides such as e.g. N-methylmorpholino-N-oxide in the presence of suitable catalysts such as e.g. Tetrapropylammonium perruthenate in inert solvents. Oxidation according to Swern and with N-methyl-morpholino-N-oxide using tetrapropylammonium perruthenate is preferred.

Für den Fall das R3a" ≠ H ist, kann jetzt nach den, dem Fachmann bekannten Methoden mit metallorganischen Verbindungen der allgemeinen Formel M-R3a", worin M für ein Alkalimetall, vorzugsweise Lithium oder ein zweiwertiges Metall MX, worin X ein Halogen repräsentiert und der Rest R3a" die oben genannte Bedeutung aufweist, der entsprechende sekundäre Alkohol hergestellt werden. Als zweiwertiges Metall ist bevorzugt Magnesium und Zink, als Halogen X ist bevorzugt Chlor, Brom und lod. Der so erhaltene sekundäre Alkohol wird durch Oxidation in das Keton der allgemeinen Formel D mit R3'≠ H nach den unter i) zu anfangs genannten Verfahren überführt. Bevorzugt ist die Oxidation mit N-Methyl-morpholino-N-oxid unter Verwendung von Tetrapropylammoniumperruthenat.In the event that R 3a "≠ H, can now by the methods known to those skilled in the art with organometallic compounds of the general formula MR 3a ", where M is an alkali metal, preferably lithium or a divalent metal MX, where X represents a halogen and the radical R 3a "has the meaning given above, the corresponding secondary alcohol is prepared. Magnesium and zinc are preferred as the divalent metal, chlorine, bromine and iodine are preferred as the halogen X. The secondary alcohol obtained in this way is converted by oxidation into the ketone of the general formula D with R3 'nach H according to the processes mentioned under i) at the beginning. Oxidation with N-methylmorpholino-N-oxide using tetrapropylammonium perruthenate is preferred.

Teilfragmente der allgemeinen Formel ABPartial fragments of the general formula AB

worin RH R^', R2a', R2b', R3a', R4', ≠', R19, R20, R2"!, R22 V und Z die bereits genannten Bedeutungen haben und PG7 ein Wasserstoffatom oder eine Schutzgruppe PG darstellt, werden aus den zuvor genannten Fragmenten A und B nach dem in Schema 3 gezeigten Verfahren erhalten.wherein RH R ^ ', R 2a ', R 2b ', R 3a ', R 4 ', ≠ ' , R1 9 , R 2 0, R 2 " !, R 22 V and Z have the meanings already mentioned and PG 7 represents a hydrogen atom or a protective group PG, are obtained from the aforementioned fragments A and B by the method shown in Scheme 3.

Schema 3Scheme 3

A-1 B AB-1 A-1 B AB-1

A-2 B AB-2A-2 B AB-2

Schritt aa (A + B => AB):Step aa (A + B => AB):

Die Verbindung B, worin W die Bedeutung eines Sauerstoffatomes hat und eventuell vorhandene zusätzliche Carbonylgruppen geschützt sind, wird mit dem Enolat einer Carbonylverbindung der allgemeinen Formel A alkyliert. Das Enolat wird durch Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Lithiumhexamethyldisilazan bei niedrigen Temperaturen hergestellt.The compound B, in which W has the meaning of an oxygen atom and any additional carbonyl groups present are protected, is alkylated with the enolate of a carbonyl compound of the general formula A. The enolate is formed by the action of strong bases such as e.g. Lithium diisopropylamide, lithium hexamethyldisilazane produced at low temperatures.

Teilfragmente der allgemeinen Formel BCPartial fragments of the general formula BC

BC,BC,

worin R3a", R4', R5', R6, R7, R27, G und W die bereits genannten Bedeutungen haben, werden aus den zuvor beschriebenen Fragmenten B und C nach dem in Schema 4 gezeigten Verfahren erhalten.where R 3a ", R 4 ', R 5 ', R 6 , R 7 , R 27 , G and W have the meanings already mentioned, are obtained from the fragments B and C described above by the process shown in Scheme 4.

Schema 4Scheme 4

Schritt ab (B + C => BC): Step from (B + C => BC):

Die Verbindung C, in der R23 die Bedeutung eines Wittigsalzes hat und eventuell vorhandene zusätzliche Carbonylgruppen geschützt sind, wird durch eine geeignete Base wie z.B. n-Butyllithium, Lithiumdiisopropylamid, Kalium-tertbutanolat, Natriumoder Lithium-hexamethyldisilazid deprotoniert und mit einer Verbindung B, worin V dieThe compound C, in which R 23 has the meaning of a Wittig salt and any additional carbonyl groups which may be present are protected, is deprotonated by a suitable base such as, for example, n-butyllithium, lithium diisopropylamide, potassium tert-butoxide, sodium or lithium hexamethyldisilazide and with a compound B, in which V the

Bedeutung von Sauerstoff und W die Bedeutung zweier Alkoxygruppen OR2^, einer C2-C-)o-Alkylen-α,ω-dioxygruppe, die geradkettig oder verzweigt sein kann oderMeaning of oxygen and W the meaning of two alkoxy groups OR 2 ^, a C2-C-) o-alkylene-α, ω-dioxy group, which can be straight-chain or branched or

H/OR26 hat, umsetzt.H / OR 26 has implemented.

Teilfragmente der allgemeinen Formel ABC (AB + C)Partial fragments of the general formula ABC (AB + C)

ABC-1 bzw. ABC-2,ABC-1 or ABC-2,

worin Rla', Rl b', R2a', R ', R3a', R4', R5', R6, R7; R19 R20, R21, R22 G- und z die bereits genannten Bedeutungen haben und PG7 ein Wasserstoffatom oder eine Schutzgruppe PG darstellt, werden aus den zuvor beschriebenen Fragmenten AB und C nach dem in Schema 5 und Schema 6 gezeigten Verfahren erhalten.wherein Rl a ', Rl b ', R 2a ', R', R 3a ', R 4 ', R5 ', R6, R7 ; R 19 R20, R 21, R 22 G - and z have the meanings already mentioned and PG 7 represents a hydrogen atom or a protective group PG are obtained from the fragments AB and C described above by the process shown in Scheme 5 and Scheme 6.

Schema 5Scheme 5

AB-1 ABC-1 AB-1 ABC-1

AB-2 C ABC-2AB-2 C ABC-2

Schritt ac (AB + C => ABC):Step ac (AB + C => ABC):

Die Verbindung C, in der R23 die Bedeutung eines Wittigsalzes hat und eventuell vorhandene zusätzliche Carbonylgruppen gegebenenfalls geschützt sind, wird durch eine geeignete Base wie z.B. n-Butyllithium, Lithiumdiisopropylamid, Kalium- tertbutanolat, Natrium- oder Lithium-hexamethyldisilazid deprotoniert und mit einer Verbindung AB, worin V die Bedeutung eines Sauerstoffatomes hat, umgesetzt.The compound C, in which R 23 has the meaning of a Wittig salt and any additional carbonyl groups that may be present are protected, is deprotonated by a suitable base, such as, for example, n-butyllithium, lithium diisopropylamide, potassium tert-butoxide, sodium or lithium hexamethyldisilazide, and with a compound AB, where V has the meaning of an oxygen atom, implemented.

Schema 6Scheme 6

A-1 BC ABC-1A-1 BC ABC-1

Schritt ad (A+BC => ABC):Step ad (A + BC => ABC):

Die Verbindung BC, worin W die Bedeutung eines Sauerstoffatomes hat und eventuell vorhandene zusätzliche Carbonylgruppen geschützt sind, wird mit dem Enolat einer Carbonylverbindung der allgemeinen Formel A alkyliert. Das Enolat wird durch Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Lithiumhexamethyldisilazan bei niedrigen Temperaturen hergestellt. Darstellung der Teilfragmente AD:The compound BC, in which W has the meaning of an oxygen atom and any additional carbonyl groups which may be present are protected, is alkylated with the enolate of a carbonyl compound of the general formula A. The enolate is produced by the action of strong bases such as lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures. Representation of the partial fragments AD:

Teilfragmente der allgemeinen Formel ADPartial fragments of the general formula AD

AD-1 AD-2AD-1 AD-2

worin Ria*, Rlb', R2a'> ^2^ R3a* f R4'f R5"; R19 R20, R27', G « und z die bereits genannten Bedeutungen haben, werden aus den zuvor beschriebenen Fragmenten A und D nach dem in Schema 7 gezeigten Verfahren erhalten.wherein Ria * , Rlb ', R 2a'> ^ 2 ^ R 3a * f R 4 ' f R 5 "; R 19 R20, R27', G « and z have the meanings already mentioned, the fragments A and D obtained by the method shown in Scheme 7.

Schema 7Scheme 7

A-1 AD-1A-1 AD-1

A-2 AD-2 Schritt a (A+ D =* AD):A-2 AD-2 Step a (A + D = * AD):

Die Verbindung D wird mit dem Enolat einer Carbonylverbindung der allgemeinen Formel A alkyliert. Das Enolat wird durch Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Lithiumhexamethyldisilazan bei niedrigen Temperaturen hergestellt.The compound D is alkylated with the enolate of a carbonyl compound of the general formula A. The enolate is formed by the action of strong bases such as e.g. Lithium diisopropylamide, lithium hexamethyldisilazane produced at low temperatures.

Die Überführung von den Fragmenten ABC bzw. AD in Verbindungen der allgemeinen Formel I erfolgt nach den im folgenden beschriebenen Verfahren. Der einzige Unterschied zwischen den Fragmenten ABC und AD besteht darin, daß in den Fragmenten ABC der Rest R5' alle Bedeutungen von R^ außer Halogen und Cyano heben kann, während in den Fragmenten AD Rp" Halogen oder Cyano bedeutet.The fragments ABC and AD are converted into compounds of the general formula I by the processes described below. The only difference between the fragments ABC and AD is that in the fragments ABC the residue R5 'can raise all meanings of R ^ except halogen and cyano, while in the fragments AD Rp "means halogen or cyano.

Schritt ae (ABC-1 oder AD-1= I): Die Verbindungen ABC-1 oder AD-1, in denen R19 eine Carbonsäure CO2H und R27 eine Hydroxylgruppe oder eine Aminogruppe darstellt, setzt man nach den, dem Fachmann bekannten Methoden für die Bildung großer Macrolide bzw. Marolactame zu Verbindungen der Formel I, in denen A-Y die Bedeutung einer O-(C=O)-Gruppe oderStep ae (ABC-1 or AD-1 = I): The compounds ABC-1 or AD-1, in which R 19 represents a carboxylic acid CO2H and R 27 represents a hydroxyl group or an amino group, are set by the methods known to the person skilled in the art for the formation of large macrolides or marolactams to give compounds of the formula I in which AY has the meaning of an O - (C = O) group or

NR2 -C(C=O)-Gruppe besitzt, um. Beispielsweise bevorzugt für die Lactonbildung wird die in "Reagents for Organic Synthesis, Vol. 16, p 353" beschriebene Methode unterNR 2 -C (C = O) group has to. For example, preferred for lactone formation is the method described in "Reagents for Organic Synthesis, Vol. 16, p 353"

Verwendung von 2,4,6-Trichlorbenzoesäurechlorid und geeigneten Basen wie z.B.Use of 2,4,6-trichlorobenzoic acid chloride and suitable bases such as e.g.

Triethylamin, 4-Dimethylaminopyridin, Natriumhydrid. Beispielsweise bevorzugt für dieTriethylamine, 4-dimethylaminopyridine, sodium hydride. For example, preferred for the

Lactambildung wird die Umsetzung der Aminosäure (R^9 eine Carbonsäure CO2H undLactam formation is the implementation of the amino acid (R ^ 9 a carboxylic acid and CO2H

R27 eine NHR29-Gruppe) mit Diphenylphosphorylazid in Gegenwart einer Base.R 27 is an NHR 29 group) with diphenylphosphoryl azide in the presence of a base.

Schritt af (ABC-1 oder AD-1=> I):Step af (ABC-1 or AD-1 => I):

Die Verbindungen ABC-1 oder AD-1 , in denen R19 eine Gruppe CH2OH und R27 eineThe compounds ABC-1 or AD-1, in which R 19 is a group CH2OH and R 27 is a

Hydroxylgruppe darstellt, lassen sich vorzugsweise unter Verwendung vonRepresents hydroxyl group, preferably using

Triphenylphosphin und Azodiestern wie beispielsweise Azodicarbonsäurediethylester zu Verbindungen der Formel I, in denen A-Y die Bedeutung einer O-CH2-Gruppe hat, umsetzen.Convert triphenylphosphine and azodiesters such as, for example, diethyl azodicarboxylate to compounds of the formula I in which A-Y has the meaning of an O-CH2 group.

Die Verbindungen ABC oder AD, in denen R19 eine Gruppe CH2-Hal oderThe compounds ABC or AD in which R 19 is a group CH2-Hal or

CH2θSθ2Alkyl oder CH2OSO2A1 I oder CH2θSO2Aralkyl und R27 eineCH2θSθ2alkyl or CH2OSO2A1 I or CH2θSO 2 aralkyl and R 27 a

Hydroxylgruppe darstellt, lassen sich nach Deprotonierung mit geeigneten Basen wie beispielsweise Natriumhydrid, n-Buthyllithium, 4-Dimethylaminopyridin, Hünig-Base, Alkylihexamethyldisilazanen zu Verbindungen der Formel I, in denen A-Y die Bedeutung einer O-CH2-Gruppe hat, zyklisieren.Represents hydroxyl group, after deprotonation with suitable bases such as sodium hydride, n-butyllithium, 4-dimethylaminopyridine, Hünig base, Cyclize alkylihexamethyldisilazanes to compounds of formula I in which AY has the meaning of an O-CH2 group.

Schritt ag (ABC-2 oder AD-2=» I): Die Verbindungen ABC-2 oder AD-2, in denen R2"1 und R22 gemeinsam einStep ag (ABC-2 or AD-2 = »I): The compounds ABC-2 or AD-2, in which R 2" 1 and R 22 together

Sauerstoffatom und R27 eine NR29Sθ2CH3~Gruppe darstellt, lassen sich durchOxygen atom and R 27 represents an NR 29 Sθ2CH3 ~ group, can be

Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Lithiumhexamethyldisilazan bei niedrigen Temperaturen zum Sulfonamid 1, in dem A-Y die Bedeutung einerExposure to strong bases such as Lithium diisopropylamide, lithium hexamethyldisilazane at low temperatures to sulfonamide 1, in which A-Y the meaning of a

NR29S02-Gruppe hat, zyklisieren.NR 29 S02 group, cyclize.

Schritt ah (ABC-2 oder AD-2^ I):Step ah (ABC-2 or AD-2 ^ I):

Die Verbindungen ABC-2 oder AD-2, in denen R21 und R22 gemeinsam einThe compounds ABC-2 or AD-2, in which R 21 and R 22 together

Sauerstoffatom und R27 eine O-C(=O)CH3-Gruppe darstellt, lassen sich durchOxygen atom and R 27 represents an OC (= O) CH3 group, can be

Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Alkalihexamethyldisilazan bei niedrigen Temperaturen zum Lacton I, in dem A-Y die Bedeutung einer O-C(=O)- Gruppe hat, zyklisieren.Exposure to strong bases such as Cyclize lithium diisopropylamide, alkali hexamethyldisilazane at low temperatures to lactone I, in which A-Y has the meaning of an O-C (= O) group.

Schritt ah (ABC-2 oder AD-2=> I):Step ah (ABC-2 or AD-2 => I):

Die Verbindungen ABC-2 oder AD-2, in denen R2^ und R22^ gemeinsam ein Sauerstoffatom und R27 eine CH2C(=O)CH3-Gruppe darstellt, lassen sich durchThe compounds ABC-2 or AD-2, in which R 2 ^ and R 22 ^ together represent an oxygen atom and R 27 represents a CH2C (= O) CH3 group, can be passed through

Einwirkung starker Basen wie z.B. Lithiumdiisopropylamid, Alkalihexamethyldisilazan bei niedrigen Temperaturen zum Lacton I, in dem A-Y die Bedeutung einer CH2C(=O)-Exposure to strong bases such as Lithium diisopropylamide, alkali hexamethyl disilazane at low temperatures to lactone I, in which A-Y has the meaning of a CH2C (= O) -

Gruppe hat, zyklisieren.Group has, cyclize.

Einführung der Stickstoffunktion für R27:Introduction of the nitrogen function for R 27 :

Die Aminogruppe NHR29 kann auf der Stufe des C-Fragmentes, des BC-Fragmentes oder des ABC-Fragmentes nach den, dem Fachmann bekannten Methoden eingeführt werden. Bevorzugt ist die Herstellung aus dem Azid (R 7= N3), das nach den, demThe amino group NHR 29 can be introduced at the level of the C fragment, the BC fragment or the ABC fragment by the methods known to the person skilled in the art. Preferred is the preparation from the azide (R 7 = N3), which according to the

Fachmann bekannten Methoden vorzugsweise unter Verwendung eines Phosphins wie beispielsweise Triphenyiphosphin in Gegenwart von Wasser in das gegebenenfalls für den weiteren Reaktionsverlauf zu schützende Amin (R27= NHR29) überführt wird. Die Einführung des Azides kann unter Anwendung der Mitsunobu-Reaktion in Gegenwart von Metallaziden vorzugsweise Natrium- oder Zinkazid oder durch Substitution einer geeigneten Abgangsgruppe wie beispielsweise eines Chlor-, Brom- oder lodatomes, einer Alkylsulfonyloxy-, einer perfluorierten Alkylsulfonyloxy-, einer Arylsulfonyloxy- oder einer Aralkylsulfonyloxy-Gruppe durch Azide erfolgen. Methods known to those skilled in the art, preferably using a phosphine such as triphenyiphosphine in the presence of water, are converted into the amine (R 27 = NHR 29 ) to be protected for the further course of the reaction. The azide can be introduced using the Mitsunobu reaction in the presence of metal azides, preferably sodium or zinc azide or by substitution of one suitable leaving group such as a chlorine, bromine or iodine atom, an alkylsulfonyloxy, a perfluorinated alkylsulfonyloxy, an arylsulfonyloxy or an aralkylsulfonyloxy group by azides.

Die flexible Funktionalisierung der beschriebenen Bausteine A, B und C gewährleistet auch eine von dem oben beschriebenen Verfahren abweichende Verknüpfungsreihenfolge, die zu den Bausteinen ABC führt. Diese Verfahren sind in der folgenden Tabelle zusammengestellt:The flexible functionalization of the described modules A, B and C also ensures a linking sequence which deviates from the method described above and which leads to the modules ABC. These procedures are summarized in the following table:

Nach diesen Verfahren lassen sich die Bausteine A, B und C, wie in Schema 10 angegeben, verknüpfen: Using these methods, building blocks A, B and C can be linked as shown in Scheme 10:

Schema 10Scheme 10

b oder eb or e

A-B-C c, d, f, g, oder iA-B-C c, d, f, g, or i

A + B A-B + C r c, d, f, g, h oder i C-A-B b oder ιA + B AB + C r c, d, f, g, h or i CAB b or ι

b oder e B-C-Ab or e B-C-A

a C-B-A ^ c> d* f> g> h oder ' b oder e B + C ► C-B + A r c, d, f, g, h oder i A-C-B a CBA ^ c> d * f> g > h or 'b or e B + C ► CB + A rc, d, f, g, h or i ACB

Freie Hydroxylgruppen in I, A, B, C, AB, BC, ABC können durch Veretherung oderFree hydroxyl groups in I, A, B, C, AB, BC, ABC can be etherified or

Veresterung, freie Carbonylgruppen durch Ketalisierung, Enoletherbildung oder Reduktion weiter funktioneil abgewandelt sein.Esterification, free carbonyl groups can be further functionally modified by ketalization, enol ether formation or reduction.

Die Erfindung betrifft alle Stereoisomeren dieser Verbindungen und auch derenThe invention relates to all stereoisomers of these compounds and also theirs

Gemische.Mixtures.

Die Erfindung betrifft weiterhin alle Prodrugformulierungen dieser Verbindungen, d.h. alle Verbindungen, die in vivo eine bioaktive Wirkstoffkomponente der allgemeinen Formel I freisetzen. Biologische Wirkungen und Anwendungsbereiche der neuen Derivate:The invention further relates to all prodrug formulations of these compounds, ie all compounds which release a bioactive active ingredient component of the general formula I in vivo. Biological effects and areas of application of the new derivatives:

Die neuen Verbindungen der Formel I sind wertvolle Pharmaka. Sie interagieren mit Tubulin, indem sie gebildete Mikrotubuli stabilisieren und sind somit in der Lage, die Zellteilung phasenspezifisch zu beeinflussen. Dies betrifft vor allem schnell wachsende, neoplastische Zellen, deren Wachstum durch interzelluläre Regelmechnismen weitgehend unbeeinflußt ist. Wirkstoffe dieser Art sind prinzipiell geeignet zur Behandlung maligner Tumoren. Als Anwendungsbereich seien beispielweise genannt die Therapie von Ovarial-, Magen-, Colon-, Adeno-, Brust-, Lungen-, Kopf- und Nacken- Karzinomen, dem malignen Melanom, der akuten lymphozytären und myelocytären Leukämie. Die erfindungsgemäßen Verbindungen eignen sich aufgrund ihrer Eigenschaften prinzipiell zur Anti-Angiogenese-Therapie sowie zur Behandlung chronischer entzündlicher Erkrankungen wie beispielsweise der Psoriasis, der multiplen Sklerose oder der Arthritis. Zur Vermeidung unkontrollierter Zellwucherungen an sowie der besseren Verträglichkeit von medizinischen Implantaten lassen sie sich prinzipiell in die hierfür verwendeten polymeren Materialien auf- bzw. einbringen. Die erfindungsgemäßen Verbindungen können alleine oder zur Erzielung. additiver oder synergistischer Wirkungen in Kombination mit weiteren in der Tumortherapie anwendbaren Prinzipien und Substanzklassen verwendet werden. Als Beispiele seien genannt die Kombination mitThe new compounds of formula I are valuable pharmaceuticals. They interact with tubulin by stabilizing formed microtubules and are therefore able to influence cell division in a phase-specific manner. This concerns above all fast growing, neoplastic cells, the growth of which is largely unaffected by intercellular control mechanisms. In principle, active substances of this type are suitable for the treatment of malignant tumors. Areas of application include the therapy of ovarian, stomach, colon, adeno, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. Due to their properties, the compounds according to the invention are suitable in principle for anti-angiogenesis therapy and for the treatment of chronic inflammatory diseases such as, for example, psoriasis, multiple sclerosis or arthritis. In order to avoid uncontrolled cell growth on and the better compatibility of medical implants, they can in principle be applied or incorporated into the polymeric materials used for this. The compounds according to the invention can be used alone or to achieve them. additive or synergistic effects can be used in combination with other principles and substance classes applicable in tumor therapy. Examples include the combination with

• Platinkomplexen wie z.B. Cisplatin, Carboplatin,Platinum complexes such as Cisplatin, carboplatin,

• interkalierenden Substanzen z.B. aus der Klasse der Anthracycline wie z.B. Doxorubicin oder aus der Klasse der Antrapyrazole wie z.B. CI-941 ,Intercalating substances e.g. from the class of anthracyclines such as Doxorubicin or from the class of antrapyrazoles such as e.g. CI-941,

• mit Tubulin interagierenden Substanzen z.B. aus der Klasse der Vinka-Alkaloide wie z.B. Vincristin, Vinblastin oder aus der Klasse der Taxane wie z.B. Taxol, Taxotere oder aus der Klasse der Makrolide wie z.B. Rhizoxin oder andere Verbindungen wie z.B. Colchicin, Combretastatin A-4, Discodermolid und seine Analoga,Substances interacting with tubulin e.g. from the class of Vinka alkaloids such as Vincristine, vinblastine or from the taxane class such as Taxol, Taxotere or from the macrolide class such as e.g. Rhizoxin or other compounds such as e.g. Colchicine, combretastatin A-4, discodermolide and its analogues,

• DNA Topoisomeraseinhibitoren wie z.B. Camptothecin, Etoposid, Topotecan, Teniposid, • Folat- oder Pyrimidin-Antimetaboliten wie z.B. Lometrexol, Gemcitubin,DNA topoisomerase inhibitors such as e.g. Camptothecin, etoposide, topotecan, teniposide, folate or pyrimidine antimetabolites such as e.g. Lometrexol, gemcitubin,

• DNA alkylierenden Verbindungen wie z.B. Adozelesin, Dystamycin A,DNA alkylating compounds such as e.g. Adozelesin, dystamycin A,

• Inhibitoren von Wachstumsfaktoren (z.B. von PDGF, EGF, TGFb, EGF) wie z.B. Somatostatin, Suramin, Bombesin-Antagonisten,Inhibitors of growth factors (e.g. PDGF, EGF, TGFb, EGF) such as e.g. Somatostatin, suramin, bombesin antagonists,

• . Inhibitoren der Protein Tyrosin Kinase oder der Protein Kinasen A oder C wie z.B. Erbstatin, Genistein, Staurosporin, llmofosin, 8-CI-cAMP, • Antihormonen aus der Klasse der Antigestagene wie z.B. Mifepriston, Onapriston oder aus der Klasse der Antiöstrogene wie z.B. Tamoxifen oder aus der Klasse der Antiandrogene wie z.B. Cyproteronacetat,•. Inhibitors of protein tyrosine kinase or protein kinases A or C such as erbstatin, genistein, staurosporin, llmofosin, 8-CI-cAMP, Anti-hormones from the class of antigestagens such as mifepristone, onapristone or from the class of anti-estrogens such as tamoxifen or from the class of anti-androgens such as cyproterone acetate,

• Metastasen inhibierenden Verbindungen z.B. aus der Klasse der Eicosanoide wie z.B. PGI2, PGE^, 6-Oxo-PGE-| sowie deren stabiler Derivate (z.B. Iloprost,Metastasis inhibiting compounds e.g. from the class of eicosanoids such as PGI2, PGE ^, 6-oxo-PGE- | as well as their stable derivatives (e.g. Iloprost,

Cicaprost, Misoprostol).Cicaprost, misoprostol).

• Inhibitoren onkogener RAS-Proteine, welche die mitotische Signaltransduktion beeinflussen wie beispielsweise Inhibitoren der Farnesyl-Protein-Transferase,Inhibitors of oncogenic RAS proteins which influence mitotic signal transduction, for example inhibitors of farnesyl protein transferase,

• natürlichen oder künstlich erzeugten Antikörpern, die gegen Faktoren bzw. deren Rezeptoren, die das Tumorwachstum fördern, gerichtet sind wie beispielsweise der erbB2-Antikörper.Natural or artificially produced antibodies which are directed against factors or their receptors which promote tumor growth, such as the erbB2 antibody.

Die Erfindung betrifft auch Arzneimittel auf Basis der pharmazeutisch verträglichen, d.h. in den verwendeten Dosen nicht toxischen Verbindungen der allgemeinen Formel I, gegebenenfalls zusammen mit den üblichen Hilfs- und Trägerstoffen.The invention also relates to pharmaceuticals based on the pharmaceutically acceptable, i.e. in the doses used, non-toxic compounds of the general formula I, if appropriate together with the customary auxiliaries and carriers.

Die erfindungsgemäßen Verbindungen können mit Liposomen verkapselt oder in ein α-, ß- oder γ-Cyclodextrinclathrat eingeschlossen sein.The compounds according to the invention can be encapsulated with liposomes or enclosed in an α-, β- or γ-cyclodextrin clathrate.

Die erfindungsgemäßen Verbindungen können nach an sich bekannten Methoden der Galenik zu pharmazeutischen Präparaten für die enterale, percutane, parenterale oder lokale Applikation verarbeitet werden. Sie können in Form von Tabletten, Dragees, Gelkapseln, Granulaten, Suppositorien, Implantaten, injizierbaren sterilen wäßrigen oder öligen Lösungen, Suspensionen oder Emulsionen, Salben, Cremes und Gelen verabreicht werden. Der oder die Wirkstoffe können dabei mit den in der Galenik üblichen Hilfsstoffen wie z.B. Gummiarabikum, Talk, Stärke, Mannit, Methylcellulose, Laktose, Tensiden wie Tweens oder Myrj, Magnesiumstearat, wäßrigen oder nicht wäßrigen Trägern, Paraffinderivaten, Netz-, Dispergier-, Emulgier-, Konservierungsmitteln und Aromastoffen zur Geschmackskorrektur (z.B. etherischen Ölen) gemischt werden. Die Erfindung betrifft somit auch pharmazeutische Zusammensetzungen, die als Wirk- stoff zumindest eine erfindungsgemäße Verbindung enthalten. Eine Dosiseinheit enthält etwa 0,1-100 mg Wirkstoff(e). Die Dosierung der erfindungsgemäßen Verbindungen liegt beim Menschen bei etwa 0,1-1000 mg pro Tag.The compounds according to the invention can be processed into pharmaceutical preparations for enteral, percutaneous, parenteral or local application according to known galenical methods. They can be administered in the form of tablets, dragees, gel capsules, granules, suppositories, implants, injectable sterile aqueous or oily solutions, suspensions or emulsions, ointments, creams and gels. The active ingredient (s) can be combined with the auxiliary agents commonly used in galenics, e.g. Gum arabic, talc, starch, mannitol, methyl cellulose, lactose, surfactants such as tweens or myrj, magnesium stearate, aqueous or non-aqueous vehicles, paraffin derivatives, wetting, dispersing, emulsifying, preserving agents and flavoring agents for flavor correction (e.g. essential oils). The invention thus also relates to pharmaceutical compositions which contain at least one compound according to the invention as active ingredient. One dose unit contains about 0.1-100 mg of active ingredient (s). The dosage of the compounds according to the invention in humans is about 0.1-1000 mg per day.

Die nachfolgenden Beispiele dienen der näheren Erläuterung der Erfindung, ohne sie darauf einschränken zu wollen: Beispiel 1 :The following examples serve to explain the invention in more detail without wishing to restrict it: Example 1 :

4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -f luor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-f luor-2- (2-methyl-4-thiazolyl) ethenyl) -5,5,7,9,13-pentamethylcyclohexadec-13-ene-2,6-dione

Beispiel 1aExample 1a

(R)-1-(Tetrahydro-2H-pyran-2-yl(oxy))-propan-2-ol(R) -1- (tetrahydro-2H-pyran-2-yl (oxy)) - propan-2-ol

Eine Lösung von 5g (65,70 mmol) R-1 ,2-Propandiol, 6,15 ml (68 mmol) 3,4-Dihydro-2H- pyran und 0,2g p-Toluolsulfonsäure-Pyridiniumsalz in 100ml Dichlormethan wird 20 Stunden bei 25°C gerührt. Anschließend wird durch Zugabe von Triethylamin neutraliert und dann die Reaktionslösung im Vakuum eingegengt. Nach Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan werden 7,08g (44,18 mmol; 67%) 1a erhalten. 1H-NMR (CDCI3): δ = 1,13 (3H), 1,48-1,59 (4H), 1 ,70-1 ,90 (2H), 3,40-4,00 (5H) 4,55A solution of 5g (65.70 mmol) of R-1, 2-propanediol, 6.15 ml (68 mmol) of 3,4-dihydro-2H-pyran and 0.2 g of p-toluenesulfonic acid pyridinium salt in 100 ml of dichloromethane is used for 20 hours stirred at 25 ° C. It is then neutralized by adding triethylamine and then the reaction solution is concentrated in vacuo. After column chromatography on silica gel with a mixture of ethyl acetate / hexane, 7.08 g (44.18 mmol; 67%) 1a are obtained. 1 H-NMR (CDCI 3 ): δ = 1.13 (3H), 1.48-1.59 (4H), 1.70-1, 90 (2H), 3.40-4.00 (5H) 4.55

(1H) ppm.(1H) ppm.

Beispiel 1bExample 1b

(5R)-5-Methyl-4-oxa-6-(tetrahydro-2H-pyran-2-yl(oxy))hexansäureethylester(5R) -5-methyl-4-oxa-6- (tetrahydro-2H-pyran-2-yl (oxy)) hexanoic acid ethyl ester

Eine Lösung aus 7,08g (44,18 mmol) der unter 1a beschriebenen Verbindung, 95 mlA solution of 7.08 g (44.18 mmol) of the compound described in 1a, 95 ml

(877mmol) Acrylsäureethylester, 3,5 ml wäßrige Tetrabutylammoniumhydroxidlösung (10%ig), 180 ml 50%ige wäßrige Natriumhydroxidlösung in 300 ml Toluol wird 2 Stunden bei 25°C gerührt. Danach wird die Lösung auf Eiswasser gegossen. Man extrahiert mit Ethylacetat, wäscht die organische Phase mit gesättigter wäßriger Natriumchloridlösung, trocknet über Natriumsulfat und engt im Vakuum ein. Säulenchromatographie des erhaltenen Rohprodukts an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan ergibt 7,704g (29,60 mmol; 67%) 1b. H-NMR (CDCI3): δ = 1,12-1,20 (3H), 1,27 (3H), 1,48-1,90 (6H), 2,58 (2H), 3,30-4,00 (7H), 4,15 (2H), 4,60+4,70 (1H) ppm.(877mmol) ethyl acrylate, 3.5 ml aqueous tetrabutylammonium hydroxide solution (10%), 180 ml 50% aqueous sodium hydroxide solution in 300 ml toluene is stirred at 25 ° C for 2 hours. Then the solution is poured onto ice water. It is extracted with ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. Column chromatography of the crude product obtained on silica gel with a mixture of ethyl acetate / hexane gives 7.704 g (29.60 mmol; 67%) 1b. H-NMR (CDCI3): δ = 1.12-1.20 (3H), 1.27 (3H), 1.48-1.90 (6H), 2.58 (2H), 3.30-4 , 00 (7H), 4.15 (2H), 4.60 + 4.70 (1H) ppm.

Beispiel 1c (5R)-5-Methyl-4-Oxa-6-(tetrahydro-2H-pyran-2-yl(oxy))hexan-1-olExample 1c (5R) -5-methyl-4-oxa-6- (tetrahydro-2H-pyran-2-yl (oxy)) hexan-1-ol

Eine Lösung von 7,704 g (29,60 mmol) 1b in 70 ml Tetrahydrofuran wird bei 0°C zu einer Suspension von 1,7 g (44,80 mmol) Lithiumaluminiumhydrid in 100 ml Tetrahydrofuran getropft. Man läßt eine Stunde bei 0°C nachrühren und addiert dann 10 ml gesättigte wäßrige Ammoniumchloridlösung. Anschließend wird über Celite filtriert und im Vakuum eingeengt. Säulenchromatographie des erhaltenen Rohprodukts an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan ergibt 6,204g (28,41 mmol; 96%) 1c.A solution of 7.704 g (29.60 mmol) of 1b in 70 ml of tetrahydrofuran is added dropwise at 0 ° C. to a suspension of 1.7 g (44.80 mmol) of lithium aluminum hydride in 100 ml of tetrahydrofuran. The mixture is stirred for one hour at 0 ° C. and then 10 ml of saturated aqueous ammonium chloride solution are added. The mixture is then filtered through Celite and concentrated in vacuo. Column chromatography of the crude product obtained on silica gel with a mixture of ethyl acetate / hexane gives 6.204 g (28.41 mmol; 96%) 1c.

1 H-NMR (CDCI3): δ = 1,10-1,22 (3H), 1,45-1,90 (8H), 2,95 (1H), 3,30-4,05 (8H), 4,58- 1 H-NMR (CDCI 3 ): δ = 1.10-1.22 (3H), 1.45-1.90 (8H), 2.95 (1H), 3.30-4.05 (8H) , 4.58-

4,70 (1H) ppm.4.70 (1H) ppm.

Beispiel 1dExample 1d

(5R)-5-Methyl-4-Oxa-6-(tetrahydro-2H-pyran-2-yI(oxy))hexan-1-al(5R) -5-methyl-4-oxa-6- (tetrahydro-2H-pyran-2-yl (oxy)) hexan-1-al

Zu einer Lösung von 3,67 ml (42,62 mmol) Oxalylchlorid in 100 ml wasserfreiemTo a solution of 3.67 ml (42.62 mmol) oxalyl chloride in 100 ml anhydrous

Dichlormethan wird bei -70°C eine Lösung von 5,99 ml (85,25 mmol) Dimethylsulfoxid, in 10 ml Dichlormethan addiert. Man rührt 3 Minuten bei -70°C nach und addiert dann eine Lösung von 6,204g (28,41 mmol) 1c in 100 ml Dichlormethan. Man läßt weitere 30 Minuten bei -70°C nachrühren. Anschließend versetzt man mit 31 ,5 ml ( 227,36 mmol) Triethylamin, läßt 30 Minuten bei -50°C reagieren. Danach wird das Reaktionsgemisch auf gesättigte wäßrige Natrϊumhydrogencarbonatlösung gegossen. Es wird mit Dichlormethan extrahiert. Die organische Phase wird mit gesättigter wäßriger Natriumchloridlösung gewaschen und über Natriumsulfat getrocknet. Das erhaltene Rohprodukt (6,15 g, 100%) wird ohne Aufreinigung in die Folgestufe eingesetzt.Dichloromethane is added at -70 ° C a solution of 5.99 ml (85.25 mmol) of dimethyl sulfoxide in 10 ml of dichloromethane. The mixture is stirred for 3 minutes at -70 ° C and then a solution of 6.204g (28.41 mmol) 1c in 100 ml dichloromethane is added. The mixture is stirred for a further 30 minutes at -70 ° C. Then 31.5 ml (227.36 mmol) of triethylamine are added and the mixture is left to react at -50 ° C. for 30 minutes. The reaction mixture is then poured onto saturated aqueous sodium bicarbonate solution. It is extracted with dichloromethane. The organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The crude product obtained (6.15 g, 100%) is used in the next step without purification.

Beispiel 1e (6R)-6-Methyl-5-oxa-7-(tetrahydro-2H-pyran-2-yl(oxy))heptan-2-olExample 1e (6R) -6-Methyl-5-oxa-7- (tetrahydro-2H-pyran-2-yl (oxy)) heptan-2-ol

19 ml (57 mmol) einer 3 molaren Lösung von Methylmagnesiumchlorid in Tetrahydrofuran werden mit 80 ml Tetrahydrofuran verdünnt. Anschließend kühlt man auf 0°C und addiert eine lösung von 6,15 g (28,41 mmol) der unter 1d beschriebenen Verbindung in 70 ml Tetrahydrofuran. Man rührt 30 Minuten bei 0°C nach und gießt dann das Reaktionsgemisch auf gesättigte wäßrige Ammoniumchloridlösung. Anschließend wird mit Ethylacetat extrahiert. Die organische Phase wird mit gesättigter wäßriger Natriumchloridlösung gewaschen und über Magnesiumsulfat getrocknet. Säulenchromatographie des erhaltenen Rohprodukts an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan ergibt 6,008g (25,86 mmol; 91%) 1e. 1H-NMR (CDCI3): δ = 1,12-1 ,22 (6H), 1,50-1 ,90 (8H), 3,32-4,07 (8H), 4,58-4,69 (1H) ppm.19 ml (57 mmol) of a 3 molar solution of methyl magnesium chloride in tetrahydrofuran are diluted with 80 ml of tetrahydrofuran. The mixture is then cooled to 0 ° C. and a solution of 6.15 g (28.41 mmol) of the compound described under 1d in 70 ml of tetrahydrofuran is added. The mixture is stirred at 0 ° C for 30 minutes and then poured the reaction mixture onto saturated aqueous ammonium chloride solution. The mixture is then extracted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. Column chromatography of the crude product obtained on silica gel with a mixture of ethyl acetate / hexane gives 6.008 g (25.86 mmol; 91%) 1e. 1 H NMR (CDCI3): δ = 1.12-1, 22 (6H), 1.50-1, 90 (8H), 3.32-4.07 (8H), 4.58-4.69 (1H) ppm.

Beispiel 1fExample 1f

(6R)-6-Methyl-5-oxa-7-(tetrahydro-2H-pyran-2-yl(oxy))heptan-2-on Eine Lösung von 6,008 g (25,86 mmol) der unter 1e beschriebenen Verbindung, 5,38 g (46,02 mmol) N-Methylmorpholino-N-oxid, 407 mg (1 ,16 mmol) Tetrapropylammoniumperruthenat in 200 ml Dichlormethan wird mit Molekularsieb (4A, ca. 600 Kugeln) versetzt. Man läßt 20 Stunden bei 25°C nachrühren. Anschließend wird im Vakuum eingeengt. Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 5,892 g (25,60 mmol; 99%) 1f.(6R) -6-methyl-5-oxa-7- (tetrahydro-2H-pyran-2-yl (oxy)) heptan-2-one A solution of 6.008 g (25.86 mmol) of the compound described under 1e, 5.38 g (46.02 mmol) N-methylmorpholino-N-oxide, 407 mg (1.16 mmol) Molecular sieve (4A, approx. 600 spheres) is added to tetrapropylammonium perruthenate in 200 ml dichloromethane. The mixture is stirred at 25 ° C for 20 hours. It is then concentrated in vacuo. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 5.892 g (25.60 mmol; 99%) 1f are obtained.

1H-NMR (CDCI3): δ = 1 ,11-1,18 (3H), 1,45-1,88 (6H), 2,18 (3H), 2,67 (2H), 3,30-3,98 1 H-NMR (CDCI 3 ): δ = 1.11-1.18 (3H), 1.45-1.88 (6H), 2.18 (3H), 2.67 (2H), 3.30 -3.98

(7H), 4,59 + 4,70 (1H) ppm.(7H), 4.59 + 4.70 (1H) ppm.

Beispiel 1g (2R,6Z,9S,10Z)-2,6-Dimethyl-9-[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]-10-fluor-11-(2- methyl-4-thiazolyl)-3-oxa-undeca-6,10-dien-1-ol-tetrahydropyran-2-yl-ether (A) (2R,6E,9S, 10Z)-2,6-Dimethyl-9-[[dimethyl(1 , 1 -dimethylethyl)silyl]oxy]-10-fluor-11 -(2- methyl-4-thiazolyl)-3-oxa-undeca-6,10-dien-1-ol-tetrahydropyran-2-yl-ether (B)Example 1g (2R, 6Z, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -10-fluoro-11- (2-methyl-4-thiazolyl) -3-oxa-undeca-6,10-dien-1-ol-tetrahydropyran-2-yl ether (A) (2R, 6E, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1 , 1-dimethylethyl) silyl] oxy] -10-fluoro-11 - (2-methyl-4-thiazolyl) -3-oxa-undeca-6,10-dien-1-ol-tetrahydropyran-2-yl ether ( B)

Zu einer Suspension von 4,498 g (7,81 mmol) (3S,4Z)-5-(2-Methylthiazol-4-yl)-3-(tert.- butyl-dimethylsilyloxy)-4-fluor-4-penten-triphenylphosphoniumiodid in 35 ml Tetrahydrofuran wird bei 0°C eine Lösung von Butyllithium in Hexan getropft (3,73 ml; 9,33 mmol; 2,5 M). Man läßt 30 Minuten nachrühren und addiert dann eine Lösung von 1 ,5 g (6,51 mmol) der unter 1f beschriebenen Verbindung in 35 ml Tetrahydrofuran. Anschließend wird 3 Stunden bei 0°C nachgerührt. Danach wird das Reaktionsgemisch auf gesättigte wäßrige Ammoniumchloridlösung gegossen. Man extrahiert mit Ethylacetat, wäscht die organische Phase mit gesättigter wäßriger Natriumchloridlösung und trocknet über Natriumsulfat. Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 1,043 g (1,98 mmol; 30 %) der Titelverbindung A und 870 mg (1,65 mmol; 25 %) der Titelverbindung B.To a suspension of 4.498 g (7.81 mmol) (3S, 4Z) -5- (2-methylthiazol-4-yl) -3- (tert-butyl-dimethylsilyloxy) -4-fluoro-4-pentene-triphenylphosphonium iodide In 35 ml of tetrahydrofuran, a solution of butyllithium in hexane is added dropwise at 3.degree. C. (3.73 ml; 9.33 mmol; 2.5 M). The mixture is stirred for 30 minutes and then a solution of 1.5 g (6.51 mmol) of the compound described under 1f in 35 ml of tetrahydrofuran is added. The mixture is then stirred at 0 ° C for 3 hours. The reaction mixture is then poured onto saturated aqueous ammonium chloride solution. It is extracted with ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 1.043 g (1.98 mmol; 30%) of the title compound A and 870 mg (1.65 mmol; 25%) of the title compound B are obtained.

Verbindung A: H-NMR (CDCI3): δ = 0,07 (6H), 0,90 (9H), 1 ,12-1 ,20 (3H), 1 ,45-1,67Compound A: H NMR (CDCI3): δ = 0.07 (6H), 0.90 (9H), 1, 12-1, 20 (3H), 1, 45-1.67

(5H), 1,71 (3H), 1 ,81 (1H), 2,24-2,51 (4H), 2,70 (3H), 3,30-3,77 (5H), 3,81-4,00 (1H), 4,17-4,27 (1H), 4,61 (1H), 5,23 (1H), 5,99-6,12 (1H), 7,34 (1H) ppm. Verbindung B: 1H-NMR (CDCI3): δ = 0,09 (6H), 0,90 (9H), 1,11-1 ,20 (3H), 1,48-1,61(5H), 1.71 (3H), 1.81 (1H), 2.24-2.51 (4H), 2.70 (3H), 3.30-3.77 (5H), 3.81 -4.00 (1H), 4.17-4.27 (1H), 4.61 (1H), 5.23 (1H), 5.99-6.12 (1H), 7.34 (1H) ppm. Compound B: 1 H NMR (CDCI3): δ = 0.09 (6H), 0.90 (9H), 1.11-1, 20 (3H), 1.48-1.61

(4H), 1 ,62 (3H), 1 ,68-1,90 (2H), 1 ,22-1 ,32 (2H), 1 ,39-1 ,47 (2H), 2,70 (3H), 3,28-3,65 (5H), 3,80-3,99 (1H), 1,16-4,27 (1H), 4,61 (1H), 5,21 (1H), 5,98-6,12 (1H), 7,33 (1H) ppm. Beispiel 1h(4H), 1, 62 (3H), 1, 68-1.90 (2H), 1, 22-1, 32 (2H), 1, 39-1, 47 (2H), 2.70 (3H) , 3.28-3.65 (5H), 3.80-3.99 (1H), 1.16-4.27 (1H), 4.61 (1H), 5.21 (1H), 5, 98-6.12 (1H), 7.33 (1H) ppm. Example 1h

(2R,6Z,9S,10Z)-2,6-Dimethyl-9-[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]-10-fIuor-11-(2- methyl-4-thiazolyl)-3-oxa-undeca-6,10-dien-1-ol(2R, 6Z, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -10-fluorine-11- (2-methyl-4-thiazolyl) -3 oxa-undeca-6,10-diene-1-ol

Eine Lösung von 1 ,043 g (1 ,98 mmol) der unter 1g beschriebenen Verbindung A und 990 mg (3,94 mmol) p-Toluolsulfonsäure-Pyridiniumsalz in 50 ml Ethanol wird 2 Stunden bei 50°C gerührt. Anschließend verdünnt man mit Dichlormethan. Die organische Phase wird mit gesättigter wäßriger Natriumhydrogencarbonatlösung und mit gesättigter wäßriger Natriumchloridlösung gewaschen. Man trcknet über Natriumsulfat Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 702 mg (1,58 mmol; 80 %) 1h. H-NMR (CDCI3): δ = 0,09 (6H), 0,91 (9H), 1,10 (3H), 1 ,72 (3H), 2,28-2,37 (2H), 2,40-A solution of 1 043 g (1.98 mmol) of the compound A described under 1 g and 990 mg (3.94 mmol) of p-toluenesulfonic acid pyridinium salt in 50 ml of ethanol is stirred at 50 ° C. for 2 hours. Then diluted with dichloromethane. The organic phase is washed with saturated aqueous sodium hydrogen carbonate solution and with saturated aqueous sodium chloride solution. It is dried over sodium sulfate. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 702 mg (1.58 mmol; 80%) are obtained for 1 hour. H-NMR (CDCI 3 ): δ = 0.09 (6H), 0.91 (9H), 1.10 (3H), 1.72 (3H), 2.28-2.37 (2H), 2nd , 40-

2,51 (2H), 2,70 (3H), 3,35-3,65 (5H), 4,17-4,28 (1 H), 5,28 (1 H), 6,00-6,13 (1H), 7,342.51 (2H), 2.70 (3H), 3.35-3.65 (5H), 4.17-4.28 (1H), 5.28 (1H), 6.00-6 , 13 (1H), 7.34

(1 H) ppm.(1H) ppm.

Beispiel 1iExample 1i

(2R,6Z,9S,10Z)-2,6-Dimethyl-9-[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]-10-fluor-11-(2- methyl-4-thiazolyl)-3-oxa-undeca-6,10-dien-1-al(2R, 6Z, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -10-fluoro-11- (2-methyl-4-thiazolyl) -3 oxa-undeca-6,10-dien-1-al

In Analogie zu Beispiel 1d werden aus 702 mg (1,58 mmol) 1h 698 mg (1,58 mmol; 100%) rohes 1i erhalten, welches ohne Aufreinigung in die Folgestufe eingesetzt wird.Analogously to Example 1d, 708 mg (1.58 mmol; 100%) of crude 1i are obtained from 702 mg (1.58 mmol) for 1 h, which is used without purification in the next stage.

1H-NMR (CDCI3): δ = 0,07 (6H), 0,88 (9H), 1 ,25 83H), 1,70 (3H), 2,23-2,48 (4H), 2,69 1 H-NMR (CDCI3): δ = 0.07 (6H), 0.88 (9H), 1, 25 83H), 1.70 (3H), 2.23-2.48 (4H), 2, 69

(3H), 3,44-3,59 (2H), 3,72 (1H), 4,14-4,26 (1H), 5,25 (1H), 5,98-6,11 (1 H), 7,31 (1H), 9,61 (1H) ppm.(3H), 3.44-3.59 (2H), 3.72 (1H), 4.14-4.26 (1H), 5.25 (1H), 5.98-6.11 (1H ), 7.31 (1H), 9.61 (1H) ppm.

Beispiel 1kExample 1k

(3S,6R,7S,8R,12Z,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1 ,3,15-tris[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-7-ol(3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1, 3,15-tris [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-7-ol

(A)(A)

(3S,6S,7R,8R, 12Z, 15S, 16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-1 ,3,7,15-tris[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-7- ol (B)(3S, 6S, 7R, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-1, 3,7,15-tris [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-7-ol (B)

Aus 473 mg (3,37 mmol) Diisopropylamin und 1 ,37 ml (3,41 mmol) einer 2,5 molaren Lösung von Butyllithium in Hexan wird in 20 ml absolutem Tetrahydrofuran Lithiumdiisopropylamid hergestellt. Man addiert dann bei -70°C eine Lösung von 1 ,273 g (3,16 mmol) (3S)-1,3-Bis[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]-4,4-dimethylheptan-5- on in 15 ml Tetrahydrofuran und läßt eine Stunde bei -40 bis -30°C nachrühren. Anschließend kühlt man erneut auf -70°C und tropft man eine Lösung von 698 mg (1 ,58 mmol) 1i in 15 ml Tetrahydrofuran langsam hinzu. Man läßt eine Stunde bei - 70°C nachrühren und gießt dann das Reaktionsgemisch auf gesättigte wäßrige Ammoniumchloridlösung. Man extrahiert mit Ethylacetat, wäscht die organische Phase mit gesättigter wäßriger Natriumchloridlösung und trocknet über Natriumsulfat. Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 494 mg (0,59 mmol; 37 %) der Titelverbindung A und 464 mg (0,55 mmol; 35 %) der Titelverbindung B.Lithium diisopropylamide is prepared in 20 ml of absolute tetrahydrofuran from 473 mg (3.37 mmol) of diisopropylamine and 1.37 ml (3.41 mmol) of a 2.5 molar solution of butyllithium in hexane. A solution of 1.273 g (3.16 mmol) of (3S) -1,3-bis [[dimethyl (1,1-dimethylethyl) silyl] oxy] -4,4-dimethylheptane is then added at -70 ° C. -5- one in 15 ml of tetrahydrofuran and allowed to stir for one hour at -40 to -30 ° C. The mixture is then cooled again to -70 ° C. and a solution of 698 mg (1, 58 mmol) 1i in 15 ml of tetrahydrofuran is slowly added dropwise. The mixture is left to stir at -70 ° C. for one hour and then the reaction mixture is poured onto saturated aqueous ammonium chloride solution. It is extracted with ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 494 mg (0.59 mmol; 37%) of the title compound A and 464 mg (0.55 mmol; 35%) of the title compound B are obtained.

Verbindung A: 1H-NMR (CDCI3): δ = 0,00-0,18 (18H), 0,84.0,99 (27H), 1,05 (3H), 1 ,08- 1,18 (6H), 1 ,21 (3H), 1 ,71 (3H), 2,20-2,47 (4H), 2,69 (3H), 3,18-3,36 (3H), 3,50-3,70 (4H), 3,90 (1H), 4,15-4,28 (1H), 5,24 (1H), 5,98-6,12 (1H), 7,32 (1H) ppm.Compound A: 1 H-NMR (CDCI3): δ = 0.00-0.18 (18H), 0.84.0.99 (27H), 1.05 (3H), 1.08-1.18 (6H) , 1, 21 (3H), 1, 71 (3H), 2.20-2.47 (4H), 2.69 (3H), 3.18-3.36 (3H), 3.50-3, 70 (4H), 3.90 (1H), 4.15-4.28 (1H), 5.24 (1H), 5.98-6.12 (1H), 7.32 (1H) ppm.

Verbindung B: 1H-NMR (CDCI3): δ = 0,02-0,15 (18H), 0,85-0,94 (27H), 1 ,05 (3H), 1 ,08Compound B: 1 H NMR (CDCI3): δ = 0.02-0.15 (18H), 0.85-0.94 (27H), 1.05 (3H), 1.08

(3H), 1 ,15 (3H), 1 ,20 (3H), 1 ,75 (3H), 2,30 (2H), 2,37-2,52 (2H), 2,70 (3H), 3,20-3,74 (7H), 4,09 (1H), 4,17-4,26 (1H), 5,25 (1H), 6,00-6,14 (1H), 7,34 (1H) ppm.(3H), 1, 15 (3H), 1, 20 (3H), 1, 75 (3H), 2.30 (2H), 2.37-2.52 (2H), 2.70 (3H), 3.20-3.74 (7H), 4.09 (1H), 4.17-4.26 (1H), 5.25 (1H), 6.00-6.14 (1H), 7.34 (1H) ppm.

Beispiel 11Example 11

(3S,6R,7S,8R,12Z,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1 ,3,7,15-tetrakis[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16- dien(3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1, 3,7,15-tetrakis [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-diene

Zu einer Lösung von 494 mg (0,59 mmol) der unter 1k beschriebenen Verbindung A in 30 ml Dichlormethan werden bei -10°C 135μl (1,17 mmol) 2,6-Lutidin und 161μl (0,70 mmol) ml Trifluormethansulfonsäure-tert.butyldimethylsilylester addiert. Man läßt 2 Stunden bei 0°C nachrühren. Danach wird das Reaktionsgemisch auf gesättigte wäßrige Natriumhydrogencarbonatlösung gegossen. Man extrahiert mit Dichlormethan, wäscht die organische Phase mit gesättigter wäßriger Natriumchloridlösung, trocknet über Natriumsulfat und engt im Vakuum ein. Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 527 g (0,55 mmol; 93 %) 11. 1H-NMR (CDCI3): δ = 0,00-0,15 (24H), 0,82-0,97 (36H), 1 ,03 (3H), 1,06 (3H), 1,11135 μl (1.17 mmol) of 2,6-lutidine and 161 μl (0.70 mmol) ml of trifluoromethanesulfonic acid are added to a solution of 494 mg (0.59 mmol) of the compound A described under 1k in 30 ml of dichloromethane at -10 ° C. -tert.butyldimethylsilylester added. The mixture is stirred at 0 ° C for 2 hours. The reaction mixture is then poured onto saturated aqueous sodium hydrogen carbonate solution. The mixture is extracted with dichloromethane, the organic phase is washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 527 g (0.55 mmol; 93%) of 11 are obtained. 1H-NMR (CDCI3): δ = 0.00-0.15 (24H), 0.82-0.97 (36H), 1.03 ( 3H), 1.06 (3H), 1.11

(3H), 1 ,28 (3H), 1 ,69 (3H), 2,22-2,46 (4H), 2,70 (3H), 3,18-3,40 (4H), 3,52-3,72 (2H), 3,80 (1H), 3,99 (1H), 4,13-4,27 (1H), 5,22 (1H), 5,99-6,12 (1H), 7,33 (1H) ppm.(3H), 1, 28 (3H), 1, 69 (3H), 2.22-2.46 (4H), 2.70 (3H), 3.18-3.40 (4H), 3.52 -3.72 (2H), 3.80 (1H), 3.99 (1H), 4.13-4.27 (1H), 5.22 (1H), 5.99-6.12 (1H) , 7.33 (1H) ppm.

Beispiel 1m (3S,6R,7S,8R, 12Z, 15S, 16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-3,7,15-tris[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-1-ol Eine Lösung von 527 mg (0,55 mmol) 11 und 128 mg (0,55 mmol) Campher-10- sulfonsäure in 20 ml eines 1 :1 Gemisches aus Dichlormethan und Methanol wird 2 Stunden bei 25°C gerührt. Anschließend addiert man einen Überschuß Triethylamin und engt im Vakuum ein. Das erhaltene Rohprodukt wird durch Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan gereinigt. Man erhält 404 mg (0,48 mmol; 87 %) 1m.Example 1m (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-1-ol A solution of 527 mg (0.55 mmol) 11 and 128 mg ( 0.55 mmol) camphor-10-sulfonic acid in 20 ml of a 1: 1 mixture of dichloromethane and methanol is stirred at 25 ° C. for 2 hours. An excess of triethylamine is then added and the mixture is concentrated in vacuo. The crude product obtained is purified by column chromatography on silica gel with a mixture of ethyl acetate / hexane. 404 mg (0.48 mmol; 87%) of 1 m are obtained.

1H-NMR (CDCI3): δ = 0,03-0,14 (18H), 0,85-0,95 (27H), 1,06 (3H), 1,08-1,15 (6H), 1,24 (3H), 1,71 (3H), 2,11-2,35 (3H), 2,42 (2H), 2,69 (3H), 3,15-3,40 (4H), 3,59-3,69 (2H), 3,99-4,06 (2H), 4,14-4,25 (1H), 5,21 (1 H), 5,99-6,12 (1H), 7,34 (1H) ppm. 1 H-NMR (CDCI 3 ): δ = 0.03-0.14 (18H), 0.85-0.95 (27H), 1.06 (3H), 1.08-1.15 (6H) , 1.24 (3H), 1.71 (3H), 2.11-2.35 (3H), 2.42 (2H), 2.69 (3H), 3.15-3.40 (4H) , 3.59-3.69 (2H), 3.99-4.06 (2H), 4.14-4.25 (1H), 5.21 (1H), 5.99-6.12 ( 1H), 7.34 (1H) ppm.

Beispiel 1n (3S,6R,7S,8R, 12Z, 15S, 16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-3,7,15-tris[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-1-al Analog zu Beispiel 1d werden aus 404 mg (0,48 mmol) der unter Beispiel 1m beschriebenen Substanz 403 mg (0,48 mmol, 100%) 1n erhalten. Die Substanz wird ohne Aufreinigung in die Folgestufe eingesetzt. 1H-NMR (CDCI3): δ = 0,02-0,13 (18H), 0,83-0,92 (27H), 1,02 (3H), 1,09 (3H), 1,11Example 1n (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12-pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-1-al Analogously to Example 1d, 404 mg (0.48 mmol) of the substance described in Example 1m, 403 mg (0.48 mmol, 100%) 1n. The substance is used in the next stage without purification. 1 H NMR (CDCI3): δ = 0.02-0.13 (18H), 0.83-0.92 (27H), 1.02 (3H), 1.09 (3H), 1.11

(3H), 1,39 (3H), 1,71 (3H), 2,10-2,31 (2H), 2,34-2,45 (3H), 2,58-2,63 (1H), 2,71 (3H), 3,14-3,40 (4H), 4,01 (1H), 4,14-4,26 (1H), 4,49 (1H), 5,22 (1H), 5,99-6,12 (1H), 7,34 (1H) ppm.(3H), 1.39 (3H), 1.71 (3H), 2.10-2.31 (2H), 2.34-2.45 (3H), 2.58-2.63 (1H) , 2.71 (3H), 3.14-3.40 (4H), 4.01 (1H), 4.14-4.26 (1H), 4.49 (1H), 5.22 (1H) , 5.99-6.12 (1H), 7.34 (1H) ppm.

Beispiel 1oExample 1o

(3S,6R,7S,8R,12Z,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris[[dimethyl(1 ,1-dimethyIethyl)silyl]oxy]heptadeca-12,16-diensäure Eine Lösung von 403 mg (0,48 mmol) der unter 1n beschriebenen Substanz in 15 ml tert.Butanol wird mit 13,7 ml 2-Methyl-2-buten (27,4 mmol) versetzt. Man kühlt dann auf 2°C und addiert 3,7 ml Wasser, 198 mg (1,44 mmol) Natriumdihydrogenphosohat- Monohydrat, 336 mg Natriumchlorit (2,97 mmol) und läßt eine 1 Stunde bei 2°C nachrühren. Anschließend gießt man in gesättigte Natriumthiosulfatlösung, verdünnt mit Wasser und extrahiert mehrfach mit Ethylacetat. Die vereinigten organischen Extrakte trocknet man über Natriumsulfat und reinigt den nach Filtration und Lösungsmittelabzug erhaltenen Rückstand durch Chromatographie an feinem Kieselgel mit einem Gradientensystem aus n-Hexan und Ethylacetat. Man erhält 345 mg (0,40 mmol, 84%) 1o.(3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethyl) silyl] oxy] heptadeca-12,16-dienoic acid A solution of 403 mg (0.48 mmol) of the substance described under 1n in 15 ml tert 13.7 ml of 2-methyl-2-butene (27.4 mmol) are added to butanol. The mixture is then cooled to 2 ° C. and 3.7 ml of water, 198 mg (1.44 mmol) of sodium dihydrogen phosphate monohydrate, 336 mg of sodium chlorite (2.97 mmol) are added and the mixture is stirred for a further hour at 2 ° C. Then poured into saturated sodium thiosulfate solution, diluted with water and extracted several times with ethyl acetate. The combined organic extracts are dried over sodium sulfate and the residue obtained after filtration and removal of the solvent is purified by chromatography on fine silica gel using a Gradient system made of n-hexane and ethyl acetate. 345 mg (0.40 mmol, 84%) 10 are obtained.

1H-NMR (CDCI3): δ = 0,04-0,15 (18H), 0,86-0,94 (27H), 1,05 (3H), 1,14 (3H), 1,18 1 H NMR (CDCI 3 ): δ = 0.04-0.15 (18H), 0.86-0.94 (27H), 1.05 (3H), 1.14 (3H), 1.18

(3H), 1 ,28 (3H), 1 ,71 (3H), 2,05 (3H), 2,26-2,48 (4H), 2,63-2,71 (1 H), 2,72 (3H), 3,10- 3,42 (4H), 4,08 (1H), 4,13-4,26 (1H), 4,37 (1H), 5,23 (1H), 6,20-6,33 (1H), 7,33 (1 H) ppm.(3H), 1, 28 (3H), 1, 71 (3H), 2.05 (3H), 2.26-2.48 (4H), 2.63-2.71 (1H), 2, 72 (3H), 3.10-3.42 (4H), 4.08 (1H), 4.13-4.26 (1H), 4.37 (1H), 5.23 (1H), 6, 20-6.33 (1H), 7.33 (1H) ppm.

Beispiel 1p (3S,6R,7S,8R, 12Z, 15S, 16Z)-3,7-Bis[[dimethyl(1 ,1 -dimethylethyl)silyl]oxy]-16-fluor-15- hydroxy-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8, 12-pentamethyl-12, 16-diensäure Eine Lösung von 345 mg (0,40 mmol) 1o in 15 ml Tetrahydrofuran wird mit 6 ml einer 1 molaren lösung von Tetrabutylammoniumfluorid in Tetrahydrofuran versetzt. Man läßt eine Stunde bei 25°C nachrühren und gießt dann das reaktionsgemisch auf eiskalte gesättigte wäßrige Ammoniumchloridlösung. Man extrahiert mit Ethylacetat und wäscht die organische Phase mit 1 normaler Salzsäure und gesättigter wäßriger Natriumhydrogencarbonatlösung. Danach wird über Natriumsulfat getrocknet. Das erhaltene Rohprodukt (299 mg; 0,40 mmol; 100%) wird ohne aufreinigung in die Folgestufe eingesetzt. 1H-NMR (CDCI3): δ = 0,03-0,13 (12H), 0,86-0,92 (18H), 1 ,06 (3H), 1,11 (3H), 1,16Example 1p (3S, 6R, 7S, 8R, 12Z, 15S, 16Z) -3,7-bis [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -16-fluoro-15-hydroxy-17- (2nd -methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8, 12-pentamethyl-12, 16-dienoic acid A solution of 345 mg (0.40 mmol) 10 in 15 ml of tetrahydrofuran is 6 ml of a 1 molar solution of tetrabutylammonium fluoride in tetrahydrofuran were added. The mixture is left to stir at 25 ° C. for one hour and then the reaction mixture is poured onto ice-cold saturated aqueous ammonium chloride solution. It is extracted with ethyl acetate and the organic phase is washed with 1 normal hydrochloric acid and saturated aqueous sodium hydrogen carbonate solution. Then it is dried over sodium sulfate. The crude product obtained (299 mg; 0.40 mmol; 100%) is used in the next step without purification. 1 H NMR (CDCI3): δ = 0.03-0.13 (12H), 0.86-0.92 (18H), 1.06 (3H), 1.11 (3H), 1.16

(3H), 1 ,28 (3H), 1,73 (3H), 2,27-2,59 (6H), 2,71 (3H), 3,08-3,17 (1H), 3,30-3,49 (3H), 4,08 (1H), 4,21-4,30 (1 H), 4,37 (1H), 5,28 (1H), 6,28-6,42 (1H), 7,33 (1H) ppm.(3H), 1, 28 (3H), 1.73 (3H), 2.27-2.59 (6H), 2.71 (3H), 3.08-3.17 (1H), 3.30 -3.49 (3H), 4.08 (1H), 4.21-4.30 (1H), 4.37 (1H), 5.28 (1H), 6.28-6.42 (1H ), 7.33 (1H) ppm.

Beispiel 1qExample 1q

4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-methyl-4- thiazolyI)ethenyl)-5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazolyI) ethenyl ) -5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dione

Zu einer Lösung von 299 mg (0,40 mmol) der unter 1 p beschriebenen Verbindung 4 mlTo a solution of 299 mg (0.40 mmol) of the compound described under 1 p 4 ml

Tetrahydrofuran werden 334 μl (2,40 mmol) Triethylamin und 315 μl (2,01 mmol) 2,4,6- Trichlorbenzoylchlorid addiert. Man läßt 15 Minuten bei 25°C nachrühren und verdünnt dann mit 35 ml Toluol. Diese Lösung wird über 3 Stunden zu einer Lösung von 510 mg (4,18 mmol) N,N-Dimethylaminopyridin in 100 ml Toluol hinzugetropft. Nach vollständiger Zugabe wird eine weitere Stunde bei 25°C nachgerührt. Anschließend wird das Reaktionsgemisch im Vakuum eingeengt. Nach Säulenchromatographie werden 169 mg (0,23 mmol, 58%) der Titelverbindung erhalten. H-NMR (CDCI3): δ = 0,02-0,14 (12H), 0,85-0,93 (18H), 1,07 (3H), 1,12 (3H), 1,19-1,24Tetrahydrofuran, 334 ul (2.40 mmol) triethylamine and 315 ul (2.01 mmol) 2,4,6-trichlorobenzoyl chloride are added. The mixture is stirred for 15 minutes at 25 ° C and then diluted with 35 ml of toluene. This solution is added dropwise over 3 hours to a solution of 510 mg (4.18 mmol) of N, N-dimethylaminopyridine in 100 ml of toluene. After the addition is complete, the mixture is stirred at 25 ° C. for a further hour. The reaction mixture is then concentrated in vacuo. After column chromatography, 169 mg (0.23 mmol, 58%) of the title compound are obtained. H-NMR (CDCI3): δ = 0.02-0.14 (12H), 0.85-0.93 (18H), 1.07 (3H), 1.12 (3H), 1.19-1 24

(6H), 1,67 (3H), 2,00-2,10 (1H), 2,41-2,65 (3H), 2,70 (3H), 2,76-2,88 (1H), 3,14-3,23 (1H), 3,39-3,53 (3H), 4,02 (1 H), 4,34 (1H), 5,23 (1H), 5,46-5,56 (1H), 6,09-6,12 (1H), 7,38 (1H) ppm.(6H), 1.67 (3H), 2.00-2.10 (1H), 2.41-2.65 (3H), 2.70 (3H), 2.76-2.88 (1H) , 3.14-3.23 (1H), 3.39-3.53 (3H), 4.02 (1H), 4.34 (1H), 5.23 (1H), 5.46-5 , 56 (1H), 6.09-6.12 (1H), 7.38 (1H) ppm.

Beispiel 1example 1

4S,7R,8S,9R,13(Z),16S(Z))-4,8-Bis[[dimethyl(1,1-dimethylethyl)silyl]oxy]-1,10-dioxa-16-4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-bis [[dimethyl (1,1-dimethylethyl) silyl] oxy] -1,10-dioxa-16

(1-fluor-2-(2-methyl-4-thiazolyl)ethenyl)-5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6- dion(1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -5,5,7,9,13-pentamethylcyclohexadec-13-ene-2,6-dione

Zu einer Lösung von 169 mg (0,23 mmol) der unter 1q beschriebenen Verbindung in 10 ml Tetrahydrofuran werden bei 0°C 530 μl HF-Pyridin-Komplex addiert. Man rührt eine Stunde bei 25°C und addiert dann erneut 530 μl HF-Pyridin-Komplex. Anschließend läßt man 10 Stunden bei 25°C nachrühren. Danach wird das Reaktionsgemisch auf gesättigte wäßrige Natriumhydrogencarbonatlösung gegossen. Man extrahiert mit Dichlormethan, wäscht die organische Phase mit gesättigter wäßriger natriumchloridlösung und trocknet über Natriumsulfat. Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan ergibt 80 mg (0,16 mmol; 69 %) der Titelverbindung. 1 H-NMR (CDCI3): δ = 1,11 (3H), 1,19 (3H), 1,23 (3H), 1 ,31 (3H), 1,71 (3H), 2,06-2,17530 μl of HF-pyridine complex are added at 0 ° C. to a solution of 169 mg (0.23 mmol) of the compound described under 1q in 10 ml of tetrahydrofuran. The mixture is stirred at 25 ° C. for one hour and then 530 μl of HF-pyridine complex are added again. Then allowed to stir at 25 ° C for 10 hours. The reaction mixture is then poured onto saturated aqueous sodium hydrogen carbonate solution. It is extracted with dichloromethane, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. Column chromatography on silica gel with a mixture of ethyl acetate / hexane gives 80 mg (0.16 mmol; 69%) of the title compound. 1 H NMR (CDCI3): δ = 1.11 (3H), 1.19 (3H), 1.23 (3H), 1.31 (3H), 1.71 (3H), 2.06-2 17

(1H), 2,38-2,68 (4H), 2,70 (3H), 2,73-2,87 (1 H), 3,00 (1 H), 3,19-3,31 (2H), 3,48 (1 H), 3,74-3,84 (2H), 4,12-4,22 (1H), 5,38-5,49 (1H), 6,10-6,13 (1H), 7,38 (1H) ppm.(1H), 2.38-2.68 (4H), 2.70 (3H), 2.73-2.87 (1H), 3.00 (1H), 3.19-3.31 ( 2H), 3.48 (1H), 3.74-3.84 (2H), 4.12-4.22 (1H), 5.38-5.49 (1H), 6.10-6, 13 (1H), 7.38 (1H) ppm.

Beispiel 2Example 2

(1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1 -f luor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12,16-pentamethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion (A)(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11 -dihydroxy-3- (1 -f luor-2- (2-methyl-4-thiazolyl) ethenyl) -8 , 8,10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (A)

(1 R,3S(Z),7S,10R,11 S,12R,16S)-7,11 -Dihydroxy-3-(1 -f luor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12,16-pentamethyI-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion (B)(1 R, 3S (Z), 7S, 10R, 11 S, 12R, 16S) -7.11 -dihydroxy-3- (1 -f luor-2- (2-methyl-4-thiazolyl) ethenyl) -8 , 8,10,12,16-pentamethyI-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (B)

Eine Lösung von 20 mg (0,04 mmol) der unter Beispiel 1 beschriebenen Verbindung inA solution of 20 mg (0.04 mmol) of the compound described in Example 1 in

2 ml Acetonitril wird mit 237 μl einer 1M Lösung von Natriumethylendiamin-tetracetat versetzt. Man kühlt auf 0°C und addiert dann 440 μl (4,91 mmol) 1 ,1,1-Trifluoraceton sowie ein Gemisch aus 121 mg (0,20 mmol) Oxon und 28 mg (0,33 mmol) Natriumhydrogencarbonat Man läßt 2 Stunden bei 2°C nachrühren und gießt dann auf Natriumthiosulfatlösung. Man extrahiert mit Ethylacetat, wäscht die organische Phase mit gesättigter wäßriger Natriumchloridlösung und trocknet über Natriumsulfat. Nach Säulenchromatographie an Kieselgel mit einem Gemisch aus Ethylacetat/Hexan werden 10 mg (0,019 mmol; 49 %) der Titelverbindung A sowie 5 mg (0,01 mmol; 24 %) der Titelverbindung B erhalten.2 ml of acetonitrile is mixed with 237 μl of a 1M solution of sodium ethylenediamine tetracetate. It is cooled to 0 ° C. and then 440 μl (4.91 mmol) 1, 1,1-trifluoroacetone and a mixture of 121 mg (0.20 mmol) oxone and 28 mg (0.33 mmol) are added Sodium bicarbonate is allowed to stir at 2 ° C for 2 hours and then poured onto sodium thiosulfate solution. It is extracted with ethyl acetate, the organic phase is washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. After column chromatography on silica gel with a mixture of ethyl acetate / hexane, 10 mg (0.019 mmol; 49%) of the title compound A and 5 mg (0.01 mmol; 24%) of the title compound B are obtained.

Verbindung A: 1 H-NMR (CDCI3): δ = 1 ,02 (3H), 1 ,11 (3H), 1 ,24 (3H), 1 ,30 (3H), 1,40Compound A: 1 H-NMR (CDCI3): δ = 1, 02 (3H), 1, 11 (3H), 1, 24 (3H), 1, 30 (3H), 1.40

(3H), 1,63-1 ,74 (1H), 1 ,78-1,86 (1H), 1,99-2,08 (1H), 2,23-2,31 (1 H), 2,50-2,56 (1H), 2,61-2,68 (1H), 2,72 (3H), 2,93 (1H), 3,43-3,59 (4H), 3,60-3,66 (1H), 3,72-3,78 (1H), 4,20 (1H9, 4,56 (1 H), 5,70-5,77 (1H), 6,21-6,32 (1H), 7,38 (1H) ppm.(3H), 1.63-1, 74 (1H), 1.78-1.86 (1H), 1.99-2.08 (1H), 2.23-2.31 (1H), 2nd , 50-2.56 (1H), 2.61-2.68 (1H), 2.72 (3H), 2.93 (1H), 3.43-3.59 (4H), 3.60- 3.66 (1H), 3.72-3.78 (1H), 4.20 (1H9, 4.56 (1H), 5.70-5.77 (1H), 6.21-6.32 (1H), 7.38 (1H) ppm.

Verbindung B: 1H-NMR (CDCI3): δ = 1,07 (3H), 1,14 (3H), 1,21 (3H), 1,27 (3H), 1,31Compound B: 1 H NMR (CDCI3): δ = 1.07 (3H), 1.14 (3H), 1.21 (3H), 1.27 (3H), 1.31

(3H), 1,72-1 ,81 (1 H), 1 ,83-1,91 (1H), 2,08-2,17 (1 H), 2,23-2,31 (1 H), 2,57-2,65 (2H), 2,71 (3H), 2,89 (1 H), 3,00 (1H), 3,46-3,58 (1H), 3,65 (1H), 3,83-3,90 (1H), 4,18 (1H), 5,78-5,86 (1H), 6,18-6,28 (1H), 7,40 (1H) ppm.(3H), 1.72-1, 81 (1H), 1, 83-1.91 (1H), 2.08-2.17 (1H), 2.23-2.31 (1H) , 2.57-2.65 (2H), 2.71 (3H), 2.89 (1H), 3.00 (1H), 3.46-3.58 (1H), 3.65 (1H ), 3.83-3.90 (1H), 4.18 (1H), 5.78-5.86 (1H), 6.18-6.28 (1H), 7.40 (1H) ppm.

Beispiel 3:Example 3:

4S,7R,8S,9R,13(E),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -f luor-2-(2-methyJ-4- thiazolyl)ethenyl)-5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (E), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-f luor-2- (2-methyJ-4-thiazolyl) ethenyl) -5,5,7,9,13-pentamethylcyclohexadec-13-ene-2,6-dione

Beispiel 3aExample 3a

(2R,6E,9S,10Z)-2,6-Dimethyl-9-[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]-10-fluor-11-(2- methyl-4-thiazolyl)-3-oxa-undeca-6, 10-dien-1 -ol Analog zu Beispiel 1 h werden aus 870 mg (1 ,65 mmol) der unter Beispiel 1g beschriebenen Verbindung B 600 mg (1,35 mmol; 82 %) der Titelverbindung erhalten.(2R, 6E, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -10-fluoro-11- (2-methyl-4-thiazolyl) -3 -oxa-undeca-6, 10-dien-1 -ol Analogously to Example 1 h, from 870 mg (1.65 mmol) of the compound B described under Example 1g, 600 mg (1.35 mmol; 82%) of the title compound are obtained ,

1H-NMR (CDCI3): δ = 0,08-0,12 (6H), 0,91 (9H), 1 ,09 (3H), 1,63 (3H), 2,27 (2H), 2,44 1 H-NMR (CDCI3): δ = 0.08-0.12 (6H), 0.91 (9H), 1, 09 (3H), 1.63 (3H), 2.27 (2H), 2 , 44

(2H), 2,70 (3H), 3,37-3,68 (5H), 4,17-4,29 (1H), 5,23 (1H), 5,98-6,12 (1H), 7,33 (1H) ppm.(2H), 2.70 (3H), 3.37-3.68 (5H), 4.17-4.29 (1H), 5.23 (1H), 5.98-6.12 (1H) , 7.33 (1H) ppm.

Beispiel 3bExample 3b

(2R,6E,9S, 10Z)-2,6-Dimethyl-9-[[dimethyl(1 , 1 -dimethylethyl)silyl]oxy]-10-fluor-11 -(2- methyl-4-thiazolyl)-3-oxa-undeca-6,10-dien-1-al Analog zu Beispiel 1d werden aus 600 mg (1,35 mmol) der unter 3a beschriebenen Verbindung 596 mg (1 ,35 mmol, 100%roh) der Titelverbindung erhalten.(2R, 6E, 9S, 10Z) -2,6-dimethyl-9 - [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -10-fluoro-11 - (2-methyl-4-thiazolyl) -3 oxa-undeca-6,10-dien-1-al Analogously to Example 1d, 596 mg (1.35 mmol, 100% crude) of the title compound are obtained from 600 mg (1.35 mmol) of the compound described under 3a.

Beispiel 3cExample 3c

(3S,6R,7S,8R,12E,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1 ,3,15-tris[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-7-ol (A)(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1, 3,15-tris [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-7-ol (A)

(3S,6S,7R,8R,12E,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazoIyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1 ,3,7,15-tris[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-7- ol (B)(3S, 6S, 7R, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazoIyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-1, 3,7,15-tris [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-7-ol (B)

Analog zu Beispiel 1k werden aus 596 mg (1 ,35 mmol) der unter 3b beschriebenen Verbindung 464 mg (0,55 mmol; 41 %) der Titelverbindung A und 388 mg (0,46 mmol; 34 %) der Titelverbindung B erhalten. Verbindung A: 1H-NMR (CDCI3): δ = 0,00-0,16 (18H), 0,86-0,99 (27H), 1 ,05 (3H), 1 ,11Analogously to Example 1k, 464 mg (0.55 mmol; 41%) of the title compound A and 388 mg (0.46 mmol; 34%) of the title compound B are obtained from 596 mg (1.35 mmol) of the compound described under 3b. Compound A: 1H-NMR (CDCI 3 ): δ = 0.00-0.16 (18H), 0.86-0.99 (27H), 1.05 (3H), 1.11

(3H), 1,15 (3H), 1 ,22 (3H), 1 ,62 (3H), 2,25 (2H), 2,41 (2H), 2,53 (1H), 2,69 (3H), 3,18- 3,37 (3H), 3,48-3,73 (4H), 3,90 (1H), 4,15-4,28 (1H), 5,21 (1H), 5,98-6,10 (1H), 7,33 (1 H) ppm.(3H), 1.15 (3H), 1, 22 (3H), 1, 62 (3H), 2.25 (2H), 2.41 (2H), 2.53 (1H), 2.69 ( 3H), 3.18-3.37 (3H), 3.48-3.73 (4H), 3.90 (1H), 4.15-4.28 (1H), 5.21 (1H), 5.98-6.10 (1H), 7.33 (1H) ppm.

Verbindung B: H-NMR (CDCI3): δ = 0,00-0,18 (18H), 0,84-0,97 (27H), 1,03 (3H), 1,08 (3H), 1,17 (3H), 1 ,19 (3H), 2,24 (2H), 2,43 (2H), 2,70 (3H), 3,18-3,28 (2H), 3,42-3,52 (2H), 3,57-3,73 (3H), 4,07 (1H), 4,16-4,28 (1H), 5,22 (1H), 5,99-6,12 (1 H), 7,32 (1H) ppm.Compound B: H NMR (CDCI3): δ = 0.00-0.18 (18H), 0.84-0.97 (27H), 1.03 (3H), 1.08 (3H), 1, 17 (3H), 1, 19 (3H), 2.24 (2H), 2.43 (2H), 2.70 (3H), 3.18-3.28 (2H), 3.42-3, 52 (2H), 3.57-3.73 (3H), 4.07 (1H), 4.16-4.28 (1H), 5.22 (1H), 5.99-6.12 (1 H), 7.32 (1H) ppm.

Beispiel 3dExample 3d

(3S,6R,7S,8R, 12E, 15S, 16Z)-16-Fluor-17-(2-methyl-4-thiazoIyl)-9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-1 ,3,7,15-tetrakis[[dimethyl(1 ,1-dimethylethyl)silyl]oxy]heptadeca-12,16- dien(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazoIyl) -9-oxa-5-oxo-4,4,6,8, 12- pentamethyl-1, 3,7,15-tetrakis [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12,16-diene

Analog zu Beispiel 11 werden aus 464 mg (0,55 mmol) der unter 3c beschriebenen Verbindung A 485 mg (0,51 mmol, 92%) der Titelverbindung erhalten.Analogously to Example 11, 485 mg (0.51 mmol, 92%) of the title compound are obtained from 464 mg (0.55 mmol) of the compound A described under 3c.

1H-NMR (CDCI3): δ = -0,02-0,13 (24H), 0,82-0,96 (36H), 0,98-1,04 (6H), 1,10 (3H), 1 H-NMR (CDCI3): δ = -0.02-0.13 (24H), 0.82-0.96 (36H), 0.98-1.04 (6H), 1.10 (3H) .

1 ,28 (3H), 1,62 (3H), 2,17 (2H), 2,40 (2H), 2,69 (3H), 3,20 (1H), 3,28-3,39 (3H), 3,52- 3,72 (2H), 3,80 (1H), 3,98 (1H), 4,01-4,26 (1H), 5,18 (1H), 5,98:6,11 (1H), 7,31 (1H) ppm. Beispiel 3e1, 28 (3H), 1.62 (3H), 2.17 (2H), 2.40 (2H), 2.69 (3H), 3.20 (1H), 3.28-3.39 ( 3H), 3.52-3.72 (2H), 3.80 (1H), 3.98 (1H), 4.01-4.26 (1H), 5.18 (1H), 5.98 : 6.11 (1H), 7.31 (1H) ppm. Example 3e

(3S,6R,7S,8R,12E,15S,16Z)-16-FIuor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris[[dimethyl(1,1-dimethylethyl)silyl]oxy]heptadeca-12,16-dien-1-ol Analog zu Beispiel 1m werden aus 485 mg (0,51 mmol) der unter 3d beschriebenen Verbindung 370 mg (0,44 mmol, 86 %) der Titelverbindung erhalten.(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris [[dimethyl (1,1-dimethylethyl) silyl] oxy] heptadeca-12,16-dien-1-ol Analogously to Example 1m, 485 mg (0.51 mmol) of the under Compound 3d described 370 mg (0.44 mmol, 86%) of the title compound.

1H-NMR (CDCI3): δ = 0,02-0,17 (18H), 0,84-0,97 (27H), 1 ,04 (3H), 1 ,07-1 ,14 (6H), 1,22 1 H-NMR (CDCI 3 ): δ = 0.02-0.17 (18H), 0.84-0.97 (27H), 1.04 (3H), 1.07-1, 14 (6H) , 1.22

(3H), 1,61 (3H), 2,17 (2H), 2,41 (2H), 2,70 (3H), 3,20 (1H), 3,30-3,42 (3H), 3,59-3,70 (2H), 4,02 (2H), 4,13-4,29 (1H), 5,18 (1H), 5,98-6,10 (1 H), 7,32 (1H) ppm.(3H), 1.61 (3H), 2.17 (2H), 2.41 (2H), 2.70 (3H), 3.20 (1H), 3.30-3.42 (3H), 3.59-3.70 (2H), 4.02 (2H), 4.13-4.29 (1H), 5.18 (1H), 5.98-6.10 (1H), 7, 32 (1H) ppm.

Beispiel 3fExample 3f

(3S,6R,7S,8R,12E,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyI-3,7, 15-tris[[dimethyl(1 , 1 -dimethylethyl)silyl]oxy]heptadeca-12, 16-dien-1 -al Analog zu Beispiel 1d werden aus 370 mg (0,44 mmol) der unter 3e beschriebenen Verbindung 370 mg (0,44 mmol, 100%roh) der Titelverbindung erhalten.(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyI-3,7, 15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12, 16-dien-1-al Analogously to Example 1d, 370 mg (0.44 mmol) of the under 3e described compound 370 mg (0.44 mmol, 100% crude) of the title compound.

1H-NMR (CDCI3): δ = 0,01-0,15 (18H), 0,82-0,95 (27H), 1,01 (3H), 1,05-1,12 (6H), 1,27 1 H-NMR (CDCI3): δ = 0.01-0.15 (18H), 0.82-0.95 (27H), 1.01 (3H), 1.05-1.12 (6H), 1.27

(3H), 1 ,61 (3H), 2,15 (2H), 2,42 (2H), 2,56-2,67 (1H), 2,70 (3H), 3,17 (1 H), 3,28-3,41 (3H), 4,00 (1H), 4,13-4,28 (1H), 4,40 (1H), 5,18 (1H), 5,98-6,11 (1H), 7,32 (1 H) ppm.(3H), 1.61 (3H), 2.15 (2H), 2.42 (2H), 2.56-2.67 (1H), 2.70 (3H), 3.17 (1H) , 3.28-3.41 (3H), 4.00 (1H), 4.13-4.28 (1H), 4.40 (1H), 5.18 (1H), 5.98-6, 11 (1H), 7.32 (1H) ppm.

Beispiel 3gExample 3g

(3S,6R,7S,8R,12E,15S,16Z)-16-Fluor-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris[[dimethyl(1 , 1 -dimethylethyl)silyl]oxy]heptadeca-12, 16-diensäure Analog zu Beispiel 1o werden aus 370 mg (0,44 mmol) der unter 3f beschriebenen Verbindung 302 mg (0,35 mmol, 80 %) der Titelverbindung erhalten.(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -16-fluoro-17- (2-methyl-4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12- pentamethyl-3,7,15-tris [[dimethyl (1, 1-dimethylethyl) silyl] oxy] heptadeca-12, 16-dienoic acid Analogously to Example 1o, 370 mg (0.44 mmol) of the compound described under 3f is 302 mg (0.35 mmol, 80%) of the title compound.

1H-NMR (CDCI3): δ = 0,00-0,16 (18H), 0,82-0,98 (27H), 1,05 (3H), 1 ,10 (3H), 1,15 1 H NMR (CDCI3): δ = 0.00-0.16 (18H), 0.82-0.98 (27H), 1.05 (3H), 1.10 (3H), 1.15

(3H), 1 ,21 (3H), 1 ,61 (3H), 2,15 (2H), 2,25-2,53 (3H), 2,63-2,76 (1H), 2,72 (3H), 3,17 (1H), 3,28-3,44 (3H), 4,07 (1H), 4,16-4,28 (1H), 4,34 (1H), 5,21 (1H), 6,07-6,20 (1H), 7,35 (1H) ppm.(3H), 1, 21 (3H), 1, 61 (3H), 2.15 (2H), 2.25-2.53 (3H), 2.63-2.76 (1H), 2.72 (3H), 3.17 (1H), 3.28-3.44 (3H), 4.07 (1H), 4.16-4.28 (1H), 4.34 (1H), 5.21 (1H), 6.07-6.20 (1H), 7.35 (1H) ppm.

Beispiel 3hExample 3h

(3S,6R,7S,8R, 12E, 15S, 16Z)-3,7-Bis[[dimethyl(1 , 1 -dimethylethyl)silyl]oxy]-16-fluor-15- hydroxy-17-(2-methyl-4-thiazolyl)-9-oxa-5-oxo-4,4,6,8,12-pentamethyl-12,16-diensäure Analog zu Beispiel 1p werden aus 302 mg (0,35 mmol) der unter 3g beschriebenen Verbindung 260 mg (0,35 mmol, 100%roh) der Titelverbindung erhalten.(3S, 6R, 7S, 8R, 12E, 15S, 16Z) -3,7-bis [[dimethyl (1, 1-dimethylethyl) silyl] oxy] -16-fluoro-15-hydroxy-17- (2-methyl -4-thiazolyl) -9-oxa-5-oxo-4,4,6,8,12-pentamethyl-12,16-dienoic acid Analogously to Example 1p, 260 mg (0.35 mmol, 100% crude) of the title compound are obtained from 302 mg (0.35 mmol) of the compound described under 3g.

1H-NMR (CDCI3): δ = 0,02-0,13 (12H), 0,83-0,98 (18H), 1,04 (3H), 1,08-1 ,17 (6H), 1 ,24 1 H-NMR (CDCI3): δ = 0.02-0.13 (12H), 0.83-0.98 (18H), 1.04 (3H), 1.08-1, 17 (6H), 1, 24

(3H), 1,63 (3H), 2,16 (1H), 2,22-2,35 (1H), 2,42-2,69 (3H), 2,69 (3H), 3,11 (1H), 3,30- 3,47 (3H), 3,99-4,14 (1H), 3,27-3,47 (2H), 5,22 (1H), 6,18-6,32 (1H), 7,33 (1H) ppm.(3H), 1.63 (3H), 2.16 (1H), 2.22-2.35 (1H), 2.42-2.69 (3H), 2.69 (3H), 3.11 (1H), 3.30-3.47 (3H), 3.99-4.14 (1H), 3.27-3.47 (2H), 5.22 (1H), 6.18-6, 32 (1H), 7.33 (1H) ppm.

Beispiel 3iExample 3i

4S,7R,8S,9R, 13(E), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,7,9, 13-pentamethylcyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (E), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -5,5,7,9, 13-pentamethylcyclohexadec-13-ene-2,6-dione

Analog zu Beispiel 1q werden aus 260 mg (0,35 mmol) der unter 3h beschriebenen Verbindung 175 mg (0,24 mmol, 69 %) der Titelverbindung erhalten.Analogously to Example 1q, 175 mg (0.24 mmol, 69%) of the title compound are obtained from 260 mg (0.35 mmol) of the compound described under 3 h.

1H-NMR (CDCI3): δ = 0,03-0,16 (12H), 0,85-0,94 (18H), 1,06 (3H), 1,09-1 ,16 (6H), 1 ,18 1 H-NMR (CDCI3): δ = 0.03-0.16 (12H), 0.85-0.94 (18H), 1.06 (3H), 1.09-1, 16 (6H), 1, 18

(3H), 1,63 (3H), 2,02-2,29 (2H), 2,38-2,46 (1H), 2,53-2,63 (2H), 2,67-2,82 (1H), 2,68 (3H), 3,08 (1 H), 3,33-3,48 (2H), 3,55-3,62 (1H), 4,00 (1H), 4,43 (1 H), 5,29 (1 H), 5,46- 5,57 (1H), 6,12-6,24 81H), 7,38 (1H) ppm.(3H), 1.63 (3H), 2.02-2.29 (2H), 2.38-2.46 (1H), 2.53-2.63 (2H), 2.67-2, 82 (1H), 2.68 (3H), 3.08 (1H), 3.33-3.48 (2H), 3.55-3.62 (1H), 4.00 (1H), 4th , 43 (1H), 5.29 (1H), 5.46-5.57 (1H), 6.12-6.24 (81H), 7.38 (1H) ppm.

Beispiel 3 4S,7R,8S,9R,13(E),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dion Analog zu Beispiel 1 werden aus 175 mg (0,24 mmol) der unter 3i beschriebenen Verbindung 85 mg (0,17 mmol, 71 %) der Titelverbindung erhalten.Example 3 4S, 7R, 8S, 9R, 13 (E), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ) ethenyl) -5,5,7,9,13-pentamethylcyclohexadec-13-en-2,6-dione Analogously to Example 1, 175 mg (0.24 mmol) of the compound described under 3i becomes 85 mg (0.17 mmol, 71%) of the title compound.

1H-NMR (CDCI3): δ = 1 ,06 (3H), 1 ,17 (3H), 1,24 (3H), 1 ,30 (3H), 1,69 (3H), 2,23 (2H), 2,48-2,61 (2H), 2,61-2,77 (2H), 2,70 (3H), 3,28-3,45 (3H), 3,52 (1 H), 3,67-3,79 (2H), 4,21 (1H), 5,23 (1 H), 5,53-5,63 (1 H), 6,12-6,26 (1 H), 7,39 (1 H) ppm. 1 H NMR (CDCI3): δ = 1.06 (3H), 1.17 (3H), 1.24 (3H), 1.30 (3H), 1.69 (3H), 2.23 (2H) ), 2.48-2.61 (2H), 2.61-2.77 (2H), 2.70 (3H), 3.28-3.45 (3H), 3.52 (1H), 3.67-3.79 (2H), 4.21 (1H), 5.23 (1H), 5.53-5.63 (1H), 6.12-6.26 (1H), 7.39 (1H) ppm.

Beispiel 4Example 4

(1S,3S(Z),7S,10R,11S,12R,16S)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)et enyl)-8,8,10,12,16-pentamethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion (A) (1R,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)et enyl)-8,8, 10,12, 16-pentamethyl-4, 13, 17- trioxabicyclo[14.1.0]heptadecan-5,9-dion (B)(1S, 3S (Z), 7S, 10R, 11S, 12R, 16S) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) et enyl) -8.8 , 10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (A) (1R, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) et enyl) -8.8 , 10,12, 16-pentamethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (B)

Analog zu Beispiel 2 werden aus 50 mg (0,10 mmol) der unter Beispiel 3 beschriebenen Verbindung 19 mg (0,037 mmol, 37 %) der Titelverbindung A und 14 mg (0,027 mmol, 27 %) der Titelverbindung B erhalten.Analogously to Example 2, 19 mg (0.037 mmol, 37%) of the title compound A and 14 mg (0.027 mmol, 27%) of the title compound B are obtained from 50 mg (0.10 mmol) of the compound described in Example 3.

Verbindung A: 1H-NMR (CDCI3): δ = 1 ,11 (3H), 1 ,17-1 ,25 (6H), 1 ,28 (3H), 1 ,36 (3H),Compound A: 1 H-NMR (CDCI3): δ = 1, 11 (3H), 1, 17-1, 25 (6H), 1, 28 (3H), 1, 36 (3H),

1,52-1 ,61 (1H), 2,08-2,22 (3H), 2,45 (1 H), 2,69 (3H), 2,76-2,85 (1H), 2,98-3,08 (2H), 3,17-3,37 (2H), 3,46-3,60 (2H), 3,69 (1H), 4,31 (1H), 5,61-5,73 (1H), 6,16-6,28 (1H), 7,39 (1H) ppm.1.52-1, 61 (1H), 2.08-2.22 (3H), 2.45 (1H), 2.69 (3H), 2.76-2.85 (1H), 2, 98-3.08 (2H), 3.17-3.37 (2H), 3.46-3.60 (2H), 3.69 (1H), 4.31 (1H), 5.61-5 , 73 (1H), 6.16-6.28 (1H), 7.39 (1H) ppm.

Verbindung B: 1H-NMR (CDCI3): δ = 1 ,02 (3H), 1,17 (3H), 1 ,22 (3H), 1 ,29 (3H), 1,36Compound B: 1 H NMR (CDCI3): δ = 1, 02 (3H), 1.17 (3H), 1, 22 (3H), 1, 29 (3H), 1.36

(3H), 1 ,55-1 ,79 (3H), 1 ,95-2,35 (3H), 2,47-2,63 (2H), 2,69 (3H), 2,94 (1H), 3,09 (1H), 3,16-3,27 (1 H), 3,38-3,48 (1 H), 3,54-3,69 (3H), 4,16 (1H), 4,32 (1H), 5,62-5,73 (1H), 6,19-6,32 (1 H), 7,39 (1 H) ppm. (3H), 1, 55-1, 79 (3H), 1, 95-2.35 (3H), 2.47-2.63 (2H), 2.69 (3H), 2.94 (1H) , 3.09 (1H), 3.16-3.27 (1H), 3.38-3.48 (1H), 3.54-3.69 (3H), 4.16 (1H), 4.32 (1H), 5.62-5.73 (1H), 6.19-6.32 (1H), 7.39 (1H) ppm.

Claims

Patentansprüche claims 1. Epothilon-Derivate der allgemeinen Formel I,1. epothilone derivatives of the general formula I, l, worinl, in which Rla; lb gleich oder verschieden sind und Wasserstoff, C^-C^o-Alky!, Aryl, C7- C20_AraIkyl, oder gemeinsam eine -(CH2)m-Gruppe mit m = 1 , 2, 3, 4 oder 5, oder eine -(CH2)-O-(CH2)-Gruppe,Rla ; lb are the same or different and are hydrogen, C ^ -C ^ o-alkyl, aryl, C7- C20 _ AraIkyl, or together a - (CH2) m group with m = 1, 2, 3, 4 or 5, or a - (CH2) -O- (CH2) group, R2a,R2b gleich oder verschieden sind und Wasserstoff, C^-C-i Q-Alkyl, Aryl, C7-C-20-R 2a , R 2b are the same or different and are hydrogen, C ^ -Ci Q-alkyl, aryl, C7-C-20- Aralkyl, -(CH2)rC≡C-(CH2)p-R9, -(CH2)rC=C-(CH2)p-R9, r gleich 0 bis 4, p gleich 0 bis 3,Aralkyl, - (CH 2 ) r C ≡ C- (CH 2 ) pR 9 , - (CH 2 ) rC = C- (CH 2 ) pR 9 , r is 0 to 4, p is 0 to 3, R9 Wasserstoff, C-|-C-ι Q-Alkyl, Aryl, C7-C-20-Aralkyl, C-i-C-iQ-Acyl, oder, falls p>0 ist, auch eine Gruppe OR1 °, R1 ° Wasserstoff, eine Schutzgruppe PG1 °, R3a Wasserstoff, C-| -C-| Q-Alkyl, Aryl, C7-C20-Aralkyl, R3b OH, OPG3 R 9 is hydrogen, C- | -C-ι Q-alkyl, aryl, C7-C-20-aralkyl, CiC-iQ-acyl, or, if p> 0, also a group OR 1 °, R 1 ° hydrogen, a protective group PG 1 °, R 3a is hydrogen, C- | C- | Q-alkyl, aryl, C 7 -C20 aralkyl, R 3b OH, OPG 3 R4 Wasserstoff, C-j -C-^ Q-Alkyl, Aryl, C7-C20-AralkylR 4 is hydrogen, Cj -C- ^ Q-alkyl, aryl, C7-C20-aralkyl R5 Wasserstoff, C-j-C-^ Q-Alkyl, Aryl, C7-C20-Aralkyl, Halogen, Cyano, (CH2)S-T wobei s für 1 , 2, 3 oder 4,R 5 is hydrogen, CjC- ^ Q-alkyl, aryl, C7-C20-aralkyl, halogen, cyano, (CH2) S -T where s is 1, 2, 3 or 4, T für OR11 oder Hai, R11 für Wasserstoff oder PG11 stehen, R6, R7 je ein Wasserstoffatom, gemeinsam eine zusätzliche Bindung oder ein Sauerstoffatom,T represents OR1 1 or shark, R 11 represents hydrogen or PG 11 , R6, R 7 each represent a hydrogen atom, together an additional bond or an oxygen atom, R12 R 12 G eine Gruppe -' , ein bi- oder tricyclischer Arylrest,G is a group - ' , a bi- or tricyclic aryl radical, R 2 Wasserstoff, Halogen, CN, Cι-C20-Alkyl, Aryl, C7-C20-Aralkyl, die alle substituiert sein können,R 2 is hydrogen, halogen, CN, C 1 -C 20 -alkyl, aryl, C7-C20-aralkyl, all of which can be substituted, X ein Sauerstoffatom, zwei Alkoxygruppen OR^3, eine C2-C-)Q-Alkylen-α,ω- dioxygruppe, die geradkettig oder verzweigt sein kann, H/OR^4 oder eine Gruppierung CR15R16, wobei R13 für einen Cι-C20-Alkylrest,X is an oxygen atom, two alkoxy groups OR ^ 3 , a C2-C-) Q-alkylene-α, ω-dioxy group, which can be straight-chain or branched, H / OR ^ 4 or a group CR 15 R 16 , where R 13 is a C 1 -C 20 -alkyl radical, R^4 für Wasserstoff oder eine Schutzgruppe PG^4,R ^ 4 for hydrogen or a protective group PG ^ 4 , R15J R16 -gleich oder verschieden sind und für Wasserstoff, einen C1-C20- Alkyl-, Aryl-, C7-C20-Aralkylrest stehen,R15 J R16 are the same or different and represent hydrogen, a C1-C20-alkyl, aryl, C7-C20-aralkyl radical, A-Y eine Gruppe O-C(=O), O-CH2, CH2C(=O), NR17-C(=O), NR17-SO2, R17 Wasserstoff, C-j-C-i Q-Alkyl,AY is a group OC (= O), O-CH 2 , CH 2 C (= O), NR 17 -C (= O), NR 17 -SO 2 , R 17 hydrogen, C- j -Ci Q-alkyl, Z ein Sauerstoffatom oder H/OR18, wobeiZ is an oxygen atom or H / OR 18 , where R"*8 Wasserstoff oder eine Schutzgruppe PG''3 ist, R8 OH oder OPG8 R " * 8 is hydrogen or a protective group PG ' ' 3 , R 8 OH or OPG 8 Hai Halogen, vorzugsweise Fluor, Chlor oder Brom bedeutetShark means halogen, preferably fluorine, chlorine or bromine ausgenommen derjenigen Verbindungen, in denen R2a Wasserstoff ist und R2b Wasserstoff, Alkyl oder Aryl und gleichzeitig R5 Wasserstoff, Alkyl oder Aryl und gleichzeitigexcluding those compounds in which R 2a is hydrogen and R 2b is hydrogen, alkyl or aryl and simultaneously R 5 is hydrogen, alkyl or aryl and simultaneously A-Y eine Gruppierung O-C(=O), O-CH2 oder NR17-C(=O) und gleichzeitigAY a grouping OC (= O), O-CH 2 or NR 17 -C (= O) and simultaneously G einen bi- oder tricyclischen Arylrest oder eine Gruppierung X=(CR'' )-bedeuten, wobei alle anderen Reste die angegebenen Bedeutungen haben können. G is a bi- or tricyclic aryl radical or a grouping X = (CR ' '), where all other radicals can have the meanings given. 2. Epothilon-Derivate der allgemeinen Formel I nach Anspruch 1 , nämlich2. epothilone derivatives of the general formula I according to claim 1, namely (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -f!uor-2-(2-methyl-4- thiazolyl)ethenyl)- 5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1 -f! Uor-2- (2-methyl-4- thiazolyl) ethenyl) - 5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S,1 OR, 11 S,12R, 16R)-7, 11 -Dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12,16-pentamethyl-4, 13,17-trioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 1 OR, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8 , 8, 10,12,16-pentamethyl-4, 13,17-trioxabicyclo [14.1.Ojheptadecan-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-7-ethyl-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-7-ethyl-16- (1 -fluoro-2- (2-methyl- 4-thiazolyl) ethenyl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -fluor-2-(2-methyloxazol-4- yl)ethenyl)- 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1 -fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 5,5,7,9, 13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-8,8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10, 12, 16-pentamethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-7-ethyl-16-(1-fluor-2-(2- methyloxazol-4-yl)ethenyl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-7-ethyl-16- (1-fluoro-2- (2-methyloxazole- 4-yl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -fluor-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R.16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1 -fluoro-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R.16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-fluor-2-(2-pyridyl)ethenyl)- 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 5 , 5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) - 8,8,10,12, 16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-7-ethyl-16-(1 -fluor-2-(2- pyridyl)ethenyl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-7-ethyl-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2- pyridyl)ethenyI)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-pyridyl) ethenyI) -8.8, 12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-fluor-2-(2-pyridyl)ethenyl)- 7-(prop-2-en-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-fluoro-2- (2-pyridyl) ethenyl) - 7 - (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)-10-(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) -10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(Prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 1 -aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8, 8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1 -f luor-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-f luor-2- (2-methyl-4-thiazolyl) ethenyl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8,12,16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyioxazoI-4-yl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-fluoro-2- (2-methyioxazoI-4-yl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydrόxy-7-ethyl-16-( 1 -fluor-2-(2-methyloxazol-4- yl)ethenyl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydrόxy-7-ethyl-16- (1 -fluoro-2- (2-methyloxazol-4-yl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) - 8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyloxazol-4-yI)ethenyl)- 7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyloxazol-4-yI) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-pyridyl)ethenyI)-1 -aza-10- oxa-5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-fluoro-2- (2-pyridyl) ethenyI) -1 -aza-10-oxa -5,5,7,9, 13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) - 8,8,10,12, 16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1 -fluor-2-(2-pyridyl)ethenyl)-1 - aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-fluoro-2- (2-pyridyl) ethenyl) -1 - aza -10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-fluor-2-(2- pyridyl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-pyridyl)ethenyl)-7-(prop-2- en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-fluoro-2- (2-pyridyl) ethenyl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-pyridyl) ethenyl) -7- (prop-2- en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-pyridyl) ethenyl) -10- (prop-2-ene -1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -5,5,7,9, 13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12,16-pentamethyl-4, 13, 17-trioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12,16-pentamethyl-4, 13, 17-trioxabicyclo [14.1. Ojheptadecan 5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-7-ethyl-16-(1-chlor-2-(2-methyl- 4-thiazolyl)ethenyl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-7-ethyl-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione ( 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-10-ethyl-3-( 1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-methyl-4- thiazo!yl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazo! yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8, 12,16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12,16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)- 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 5,5,7,9, 13-pentamethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10,12,16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-7-ethyI-16-(1-chlor-2-(2- methyloxazol-4-yl)ethenyl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-7-ethyI-16- (1-chloro-2- (2-methyloxazole- 4-yl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S,10R.11 S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R.11 S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa16-(1 -chlor-2-(2-pyridyl)ethenyl)- 5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa16- (1-chloro-2- (2-pyridyl) ethenyl) - 5.5 , 7,9,13--pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) - 8,8,10,12, 16-pentamethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-7-ethyl-16-(1-chlor-2-(2- pyridyl)ethenyl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-7-ethyl-16- (1-chloro-2- (2-pyridyl) ethenyl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2- pyridyl)ethenyl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclot14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-pyridyl) ethenyl) -8.8, 12,16-tetramethyl-4,13,17-trioxabicyclot14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -chlor-2-(2-pyridyl)ethenyl)- 7-(prop-2-en-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-pyridyl) ethenyl) - 7 - (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione f 1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-3-(1 -chlor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dionf 1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -chlor-2-(2-methyl-4-thiazoIyl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazoIyl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10, 1 , 16-pentamethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10, 1, 16-pentamethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecanoic 5,9-dion5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyl-4-thiazolyl)ethenyl)- 7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyloxazol-4-yl)ethenyl)- 1-aza-10-oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 1-aza -10-oxa-5,5,7,9,13-pentamethyl-Cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -8.8, 10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-7-ethyl-16-( 1 -chlor-2-(2-methyloxazol-4- yl)ethenyl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1 -chlor-2-(2-methyloxazol- 4-yl)ethenyl)-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl ) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyloxazol-4-yl)ethenyl)- 7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) - 7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-pyridyI)ethenyl)-1-aza-10- oxa-5,5,7,9,13-pentamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-chloro-2- (2-pyridyI) ethenyl) -1-aza-10-oxa -5,5,7,9,13-pentamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-pyridyl)ethenyl)- 8,8,10,12,16-pentamethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-7-ethyl-16-(1-chlor-2-(2-pyridyl)ethenyl)-1- aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) - 8,8,10,12, 16-pentamethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-7-ethyl-16- (1-chloro-2- (2-pyridyl) ethenyl) -1- aza -10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-10-ethyl-3-(1-chIor-2-(2- pyridyI)ethenyl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-10-ethyl-3- (1-chloro-2- (2-pyridyI) ethenyl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-pyridyl)ethenyl)-7-(prop-2- en-1 -yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-pyridyl) ethenyl) -7- (prop-2- en-1 -yl) -1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -chlor-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicycIo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-chloro-2- (2-pyridyl) ethenyl) -10- (prop-2 -en-1-yl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)- 7,9, 13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -fluor-2-(2-methyI-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-deca-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10, 12,16-trimethyl-8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-deca-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-7-ethyl-16-(1 - fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-7-ethyl-16- (1 - fluoro-2 - (2-methyl-4-thiazolyl) ethenyl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-10-ethyl-3-(1-fIuor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1,3-trimethylen)-4, 13,17-trioxabicyclo[14.1. Ojhepta- decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-10-ethyl-3- (1-fluorine-2- (2-methyl-4 -thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1. Ojhepta-decan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(1-fluor-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1-yl)- 5,5-(1 ,3-trimethy!en)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (1-fluoro-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethy! en) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R,16R)-7, 11 -Dihydroxy-12,16-dimethyl-3-(1 -fluor-2-(2-methyl- 4-thiazolyi)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12,16-dimethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyi ) ethenyl) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5.9- dion 4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-fluor-2-(2-methyl-4-thiazolyl)ethenyl)- 1-aza-10-oxa-7,9,13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-deca-5,9-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 1-aza- 10-oxa-7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-deca-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-7-ethyl-16-(1-fluor-2-(2- methyl-4-thiazolyl)ethenyl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-7-ethyl-16- (1-fluoro-2- (2-methyl- 4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-12, 16-dimethyl-10-ethyl-3-(1 -fluor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-12, 16-dimethyl-10-ethyl-3- (1-fluoro-2- (2-methyl -4-thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cycIohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-fluor-2-(2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13, 17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13, 17-dioxabicyclo [14.1.0] hepta-decane-5.9- dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)- 7,9, 13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-deca-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-deca-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-7-ethyl-16-(1- chlor-2-(2-methyl-4-thiazolyl)ethenyl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-7-ethyl-16- (1-chloro-2 - (2-methyl-4-thiazolyl) ethenyl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-12, 16-dimethyl-10-ethyl-3-(1 -chlor-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1,3-trimethylen)-4, 13,17-trioxabicyclo[14.1. Ojhepta- decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-12, 16-dimethyl-10-ethyl-3- (1-chloro-2- (2-methyl -4-thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1. Ojhepta-decan-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy1 , 10-dioxa-9,13-dimethyl-16-(1 -chlor-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethyien)cyclohexadec-13-en- 2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-chlor-2-(2-methyl-(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy1, 10-dioxa-9,13-dimethyl-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-chloro-2- (2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1-y!)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion4-thiazolyl) ethenyl) -10- (prop-2-en-1-y!) - 8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane 5,9-dione 4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-chlor-2-(2-methyl-4-thiazolyl)ethenyl)- 1 -aza-10-oxa-7,9,13-trimethyl-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 1 -aza- 10-oxa-7,9,13-trimethyl-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-10,12,16-trimethyl-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-deca-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -10.12, 16-trimethyl-8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-deca-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-7-ethyl-16-(1-chlor-2-(2- methyl-4-thiazolyl)ethenyl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-7-ethyl-16- (1-chloro-2- (2-methyl- 4-thiazolyl) ethenyl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12,16-dimethyl-10-ethyl-3-(1 -chlor-2-(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12,16-dimethyl-10-ethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl)ethenyl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(2-methyl-4-thiazolyl) ethenyl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R, 13(Z),16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(1 -chlor-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-chlor-2-(2-methyl- 4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyc!o[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyc! O [14.1.0] hepta-decan-5, 9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) -5,5,9,13-tetramethyl-dione cyclohexadec-13-ene-2,6- (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicydo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicydo [14.1.0] heptadecan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(prop-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methy!oxazol-4- yl)ethenyl)-10-(prop-2-en-1 -yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (prop-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methy! Oxazol-4-yl) ethenyl) - 10- (prop-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (prop-2-en-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2-ene -1 -yl) -8.8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-16-(1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( prop-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(prop- 2-en-1 -yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (prop- 2- en-1 -yl) -1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2-ene -1 -yl) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9,13-dimethyl-16-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyI-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyI)-7-(prop-2-en-1-yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec- 13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyI) -7- (prop-2-en-1-yl) -1 -aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-12, 16-dimethyl-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-en-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-12, 16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl ) ethenyl) -10- (prop-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decan-5, 9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-in-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyI)-7-(prop-2-in-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyI) -7- (prop-2-in-1-yl) - 5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-in-1-yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-in-1-yl) -8,8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(prop-2-in-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (prop-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2-in -1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cycIohexadec- 13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(prop-2-in-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( prop-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (prop -2-in-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( prop-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(prop-2-in-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (prop -2-in-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(prop- 2-in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (prop- 2- in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (prop-2-in-1-yl)-8,8, 12,16-tetramethyI-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (prop-2-in -1-yl) -8.8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (prop-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-in-1-yi)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (prop-2-in-1-yi) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (prop-2-in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S,1 OR, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 1 OR, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (1-methyl-2- (2-methyl-4- thiazolyl) ethenyl) -10- (prop-2-yn-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5 , 9-dione (4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-en-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methy!-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-en-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methy! -2- (2-methyl-4-thiazolyl) ethenyl) -10 - (but-2-en-1-yl) -8.8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(but-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (but-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but-2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(but-2-en-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (but-2-en-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S,1 OR, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-pyridy!)ethenyl)-10- (but-2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 1 OR, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-pyridy!) Ethenyl) -10- (but -2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazo!yl)ethenyl)-7-(but-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazo! Yl) ethenyl) -7 - (but-2-en-1-yl) -1-aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but -2-en-1-yl) -8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yI)ethenyl)-7-(but-2-en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yI) ethenyl) -7- ( but-2-en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(1 -methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-en-1 -yl)-8,8,12, 16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but-2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(but-2- en-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (but-2- en-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2-ene -1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9, 13-dimethyl-16-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(but-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-en-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9- dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-yn-1-yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but -2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2-methyloxazol- 4-yl)ethenyl)-7-(but-2-in-1-yl)- 5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- (but-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-in-1 -yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but -2-in-1-yl) -8,8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(1-methyl-2-(2- pyridyl)ethenyl)-7-(but-2-in-1 -yl)- 5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (1-methyl-2- (2-pyridyl) ethenyl) -7 - (but-2-in-1-yl) - 5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2 -in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1-yl)-1 -aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- ( but-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S, 10R,11 S,12R,16R)-7,11 -Dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8, 12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7.11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -10- (but-2-in-1-yl) -8,8, 12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -7- ( but-2-in-1-yl) -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyloxazol-4- yl)ethenyl)-10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyloxazol-4-yl) ethenyl) -10- (but -2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(1-methyl-2-(2-pyridyl)ethenyl)-7-(but-2- in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (1-methyl-2- (2-pyridyl) ethenyl) -7- (but-2- dione -1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-in-1-yl) (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-pyridyl)ethenyl)-10- (but-2-in-1 -yl)-8,8, 12,16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-pyridyl) ethenyl) -10- (but-2-in -1 -yl) -8.8, 12,16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-7-(but-2-in-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (1-methyl-2- (2- methyl-4-thiazolyl) ethenyl) -7- (but-2-yn-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-in-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -7- (but-2-in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -10- (but-2-in-1-yl) -8.8- (1,3-trimethylene) -4-aza-13.17-dioxabicyclo [14.1.0] hepta-decane-5.9- dion (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (prop-2-en-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -en-1 -yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-5- benzoxazolyl)-10-(prop-2-en-1 -yl)-8,8,12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-5-benzoxazolyl) -10- (prop-2 -en-1 -yl) -8,8,12,16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(prop-2-en- 1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (prop-2-en-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6- (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(prop- 2-en-1 -yl)-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-en-1 - yl) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9, 13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop-2- en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z), 16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -en-1 -yl) -1 -aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-en~1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop-2- en ~ 1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (prop-2-in-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazoIyl)-10-(prop- 2-in-1 -yl)-8,8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(prop-2-in- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8.8, 12, 16-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (prop-2-in-1 -yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(prop- 2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-in-1 -yl)-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (prop-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(prop-2-in-1 -yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (prop-2 -in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyi-5- benzoxazolyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyi-5-benzoxazolyl) -10- (prop- 2-in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5-benzoxazolyl)-7- (but-2-en-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -en-1 -yl) -5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-en-1- yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(but-2-en- 1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (but-2-en-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6- (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-en-1- yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-en-1-yl)- 5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion (1 S,3S(Z),7S,10R,11 S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-en-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decan-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-en-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13-en- 2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- en-1-yl) -8.8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)- 10-(but-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicycIo[14.1.Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 10- (but-2-in-1-yl ) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.Ojheptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzoxazolyl)-7-(but-2-in-1- yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzoxazolyl) -7- (but-2-yn-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzoxazolyl)-10-(but- 2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) -10- (but- 2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1-yl)-5,5-(1,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) - 7- (but-2-in-1-yl) -5,5 (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethylen)-4,13,17-trioxabicyclo[14.1.0]hepta- decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzoxazolyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzoxazolyl)-10-(but-2-in-1-yl)-8,8-(1 ,3-trimethy!en)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzoxazolyl) -7- (but-2 -in-1 -yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzoxazolyl) -10- (but-2- in-1-yl) -8,8- (1,3-trimethy! en) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(prop-2-en-1 -yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2 -en-1 -yl) -5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(1-methyl-2-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1 -yl)-8,8, 12, 16-tetramethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (1-methyl-2- (2-methyl-5-benzothiazolyl) -10- (prop-2 -en-1 -yl) -8.8, 12, 16-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(prop-2- en- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (prop-2-en-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-en-1- yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-en-1 -yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1-yl)-8,8-(1 ,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- en-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R, 13(Z),16S(Z))-4,8-Dihydroxy-9, 13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-en-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9, 13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (prop-2 -en-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1 S,3S(Z),7S, 10R, 11 S,12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop- 2-en-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5-benzothiazolyl)- 7-(prop-2-in-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2 -in-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-in-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(prop-2- in-1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (prop-2- in-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6- (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10- (prop-2-in-1 -y])-8,8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (prop-2-in-1 -y] ) -8.8, 12, 16-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-in-1 -yl)-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1,10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (prop-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzothiazoIyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethylen)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzothiazoIyl) -10- (prop- 2-in-1-yl) -8.8- (1,3-trimethylene) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(prop-2-in-1-yl)-1-aza-10-oxa-5,5-(1,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (prop-2 -in-1-yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(prop-2-in-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (prop-2- in-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(but-2-en-1-yl)-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1,10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (but-2 -en-1-yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-en-1-yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(but-2-en- 1 -yl)-1 -aza-10-oxa-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (but-2-en-1-yl ) -1-Aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-en-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0jheptadecan-5,9-dion (4S,7R,8S,9R, 13(Z), 16S(Z))-4,8-Dihydroxy-1 , 10-dioxa-9, 13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-en-1-yl)- 5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-en-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0jheptadecan-5,9-dione (4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9, 13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (but-2-en-1-yl) - 5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-en-1 -yl)-8,8-(1 ,3-trimethylen)-4, 13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- en-1-yl) -8,8- (1,3-trimethylene) -4, 13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-en-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13- en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (but-2 -en-1 -yl) -1 -aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-en-2,6-dione (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-12,16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-en-1-yl)-8,8-(1,3-trimethylen)-4-aza-13,17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-12,16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but-2- en-1-yl) -8,8- (1,3-trimethylene) -4-aza-13,17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-16-(2-methyl-5- benzothiazolyl)- 7-(but-2-in-1 -yl)-5,5,9, 13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-1, 10-dioxa-16- (2-methyl-5-benzothiazolyl) - 7- (but-2 -in-1 -yl) -5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-in-1-yl)-8,8,12,16-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-in-1- yl) -8,8,12,16-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-16-(2-methyl-5-benzothiazolyl)-7-(but-2-in- 1-yl)-1-aza-10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-16- (2-methyl-5-benzothiazolyl) -7- (but-2-in-1-yl ) -1-aza-dione 10-oxa-5,5,9,13-tetramethyl-cyclohexadec-13-ene-2,6- (1S,3S(Z),7S,10R,11S,12R,16R)-7,11-Dihydroxy-3-(2-methyl-5-benzothiazolyl)-10-(but- 2-in-1-yl)-8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12R, 16R) -7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-in-1-yl) -8,8,12,16-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-1 ,10-dioxa-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-in-1 -yl)-5,5-(1 ,3-trimethylen)cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-Dihydroxy-1, 10-dioxa-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) - 7- (but-2-in-1-yl) -5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-in-1-yl)-8,8-(1,3-trimethyien)-4,13,17- trioxabicyclo[14.1.0]hepta-decan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-in-1-yl) -8,8- (1,3-trimethyl) -4,13,17-trioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9R,13(Z),16S(Z))-4,8-Dihydroxy-9,13-dimethyl-16-(2-methyl-5- benzothiazolyl)-7-(but-2-in-1 -yl)-1 -aza-10-oxa-5,5-(1 ,3-trimethylen)cyclohexadec-13-en- 2,6-dion (1 S,3S(Z),7S, 10R, 11 S, 12R, 16R)-7, 11 -Dihydroxy-12, 16-dimethyl-3-(2-methyl-5- benzothiazolyl)-10-(but-2-in-1 -yl)-8,8-(1 ,3-trimethyien)-4-aza-13, 17- dioxabicyclo[14.1.0]hepta-decan-5,9-dion(4S, 7R, 8S, 9R, 13 (Z), 16S (Z)) - 4,8-dihydroxy-9,13-dimethyl-16- (2-methyl-5-benzothiazolyl) -7- (but-2 -in-1 -yl) -1-aza-10-oxa-5,5- (1,3-trimethylene) cyclohexadec-13-ene-2,6-dione (1 S, 3S (Z), 7S, 10R, 11 S, 12R, 16R) -7, 11 -dihydroxy-12, 16-dimethyl-3- (2-methyl-5-benzothiazolyl) -10- (but- 2-in-1-yl) -8,8- (1,3-trimethyl) -4-aza-13, 17-dioxabicyclo [14.1.0] hepta-decane-5,9-dione (4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-f luor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-fluorine-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 , 10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-dione 5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6- (1 S,3S(E),7S,10R,11 S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(E),7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.OJheptadecan-5,9- dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8.8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo [14.1.Ojheptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6- (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-dione 5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6- (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(E),7S,10R,11 S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E,16S(E))-4,8-Dihydroxy-7-ethyl-13-f luor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 , 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-ethyl-13-fluoror-16- (1-methyl-2- (2-methyl-4-thiazolyl)) ethenyl) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Fluor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4, 13,17-trioxabicyclo[14.1.Ojheptadecan- 5,9-dion (1 R,3S(E),7S,10R,11S,12S,16R)-16-Fluor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4, 13,17-trioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8, 12-trimethyl-4, 13,17-trioxabicyclo [14.1.Ojheptadecan-5,9-dione (1 R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4- thiazolyl) ethenyl) -8,8,12-trimethyl-4, 13,17-trioxabicyclo [14.1.Ojheptadecan-5,9-dione (4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-7-allyl-13-chlor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-allyl-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-10-allyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4,13,17-trιoxabicyclo[14.1.0]heptadecan- 5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-10-allyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8,12-trimethyl-4,13,17-trιoxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(E),7S, 10R,11 S,12S,16R)-16-Chlor-10-allyl-7,11 -dihydroxy-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4, 13,17-trioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-10-allyl-7.11 -dihydroxy-3- (1-methyl-2- (2-methyl-4 -thiazolyl) ethenyl) -8,8,12-trimethyl-4, 13,17-trioxabicyclo [14.1. Ojheptadecan 5,9-dione (4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-1,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6- (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(E),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6- (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chior-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -1, 10-dioxa-5,5,7,9-dione tetraamethyl-cyclohexadec-13-ene-2,6- (1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8.8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 ,10-dioxa-7,9-dimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1, 10-dioxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7,11 -dihydroxy-3-(1 -f luor-2-(2-methyI-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11 -dihydroxy-3- (1 -f luor-2- (2-methyl-4-thiazolyl) ethenyl) -8,8-trimethylene-10,12-dimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(Z),7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4,13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (Z), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8-trimethylene-10,12-dimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -chior-2-(2-methy)-4- thiazolyl)ethenyl)-5,5-trimethylen-1 ,10-dioxa-7,9-dimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methy) -4-thiazolyl) ethenyl) -5 , 5-trimethylene-1, 10-dioxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10,12-dimethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10, 12-dimethyl-4, 13,17- trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10, 12-dimethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -fluor-2-(2-methyl-4- oxazo!yl)ethenyl)-1 , 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-oxazo! Yl) ethenyl) - 1, 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- oxazoiyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion (1 R,3S(Z),7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(1 -fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazoiyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R, 3S (Z), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl ) -8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S(Z))-4,8-Dihydroxy-13-chlor-16-(1 -f luor-2-(2-methyl-2- pyridyl)ethenyl)-1 ,10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-f luor-2- (2-methyl-2-pyridyl) ethenyl) -1 , 10-dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-7-ethyl-13-chlor-16-(1 -chlor-2-(2-methyl-2- pyridyl)ethenyl)-1 , 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-7-ethyl-13-chloro-16- (1-chloro-2- (2-methyl-2-pyridyl) ethenyl ) -1, 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2-pyridyl) ) ethenyl) -8,8,12-trimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(Z),7S,10R,11 S,12S,16R)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S (Z), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2 -pyridyl) ethenyl) -8,8,12-trimethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1,10-dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1,10-dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S,7S, 10R, 11 S, 12S, 16S)-16-Fluor-7, 11 -dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4 , 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzothiazolyl)-1 ,10- dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-chlor-16-(2-methy!-5-benzothiazolyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1, 10- dioxa-5,5,7,9- tetraamethyl-Cyclohexadec-13-en-2,6-dione (4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methy! -5-benzothiazolyl) -1, 10-dioxa-5,5,7,9 tetramethyl-Cyclohexadec dion-13-en-2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4, 13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-ethyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1 ,10-dioxa-5,5,9-trimethyl-cycIohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-ethyl-13-chloro-16- (2-methyl-5-benzothiazolyl) - 1, 10-dioxa-5.5, 9-trimethyl-cycIohexadec dione-13-en-2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-trimethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-trimethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy- 10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12- tetramethyl-4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S)-4,8-Dihydroxy-7-allyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1 , 10-dioxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-allyl-13-chloro-16- (2-methyl-5-benzothiazolyl) - 1, 10-dioxa-5.5, 9-trimethyl-cyclohexadec-13-en-dione 2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-trimethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12-trimethyl- 4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazoIyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1 ,10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S,7S,10R,11S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo[14.1.0]heptadecan-5,9-dion (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Fluor-7, 11 -dihydroxy-3-(2-methyl-5-benzoxazoiyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8, 10, 12-tetramethyl-4, 13, 17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-fluoro-7, 11 -dihydroxy-3- (2-methyl-5-benzoxazoiyl) - 8,8,10,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1,10- dioxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1,10-dioxa-5,5,7,9- tetraamethyl-Cyclohexadec-13-en-2,6-dione (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 , 10- dioxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1, 10- dioxa-5,5,7,9- tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S,7S, 10R, 11 S, 12S, 16S)-16-ChIor-7, 11 -dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11 -dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4,13,17-trioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl- 4,13,17-trioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-13-fluor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione (4S,7R,8S,9S, 13Z, 16S(E))-4,8-Dihydroxy-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-Dihydroxy-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(E),7S, 10R, 11 S, 12S, 16S)-16-Fluor-7, 11 -dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 S, 3S (E), 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione (1 R,3S(E),7S,1 OR, 11 S, 12S, 16R)-16-Fluor-7, 11 -dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 R, 3S (E), 7S, 1 OR, 11 S, 12S, 16R) -16-fluoro-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -8.8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione (4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-Dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (4S,7R,8S,9S,13Z,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S (E)) - 4,8-Dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10, 12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.OJheptadecan- 5,9-dion (1 R,3S(E),7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8, 10, 12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.OJheptadecan-5,9-dione (1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione (4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-7-ethyl-13-fluor-16-(1-methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-ethyl-13-fluoro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1-Aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Fluor-10-ethyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-fluoro-10-ethyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(E),7S,1 OR, 11 S, 12S, 16R)-16-Fluor-10-ethyl-7, 11 -dihydroxy-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (E), 7S, 1 OR, 11 S, 12S, 16R) -16-fluoro-10-ethyl-7, 11 -dihydroxy-3- (1 -methyl-2- (2-methyl- 4-thiazolyl) ethenyl) -8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S, 13E, 16S(E))-4,8-Dihydroxy-7-allyl-13-chlor-16-(1 -methyl-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-101 -oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-dihydroxy-7-allyl-13-chloro-16- (1-methyl-2- (2-methyl-4-thiazolyl) ethenyl ) -1-Aza-101-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-10-allyl-7,11-dihydroxy-3-(1-methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8, 12-trimethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-10-allyl-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-4-thiazolyl) ) ethenyl) -8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S(E),7S, 10R, 11 S, 12S, 16R)-16-Chlor-10-allyl-7, 11 -dihydroxy-3-(1 -methyl-2-(2- methyl-4-thiazolyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S (E), 7S, 10R, 11 S, 12S, 16R) -16-chloro-10-allyl-7, 11 -dihydroxy-3- (1-methyl-2- (2-methyl-4 -thiazolyl) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(E))-4,8-Dihydroxy-13-chlor-16-(1-methyl-2-(2-methyI-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (E)) - 4,8-Dihydroxy-13-chloro-16- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(E),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (E), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(E),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-methyl-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10, 12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9- dion (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-1-aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(1R, 3S (E), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-methyl-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10, 12-tetramethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -1- aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione ( 1 S,3S(Z),7S, 10R, 11 S, 12S, 16S)-16-Chlor-7, 11 -dihydroxy-3-( 1 -fluor-2-(2-methyI-4- thiazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. Ojheptadecan- 5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7, 11 -dihydroxy-3- (1 -fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -8.8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. Ojheptadecan 5,9-dione (1 R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion(1 R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane 5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.Ojheptadecan- 5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.Ojheptadecan-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fIuor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 -aza-10-oxa-7,9-dimethyl-cyclohexadec-13-en-2,6- dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-fluorine-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1-aza-10-oxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione (1 S,3S(Z),7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1 -fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S (Z), 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl ) -8,8-trimethylene-10,12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10,12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-5,5-trimethylen-1 -aza-10-oxa-7,9-dimethyI-cyclohexadec-13-en-2,6- dion (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10,12-dimethyl-4-aza-13,17- dioxabicyclo[14.1.0Jheptadecan-5,9-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-dihydroxy-13-chloro-16- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) -5, 5-trimethylene-1-aza-10-oxa-7,9-dimethyl-cyclohexadec-13-ene-2,6-dione (1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10,12-dimethyl-4-aza-13,17-dioxabicyclo [14.1.0heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-chlor-2-(2-methyl-4- thiazolyl)ethenyl)-8,8-trimethylen-10, 12-dimethyl-4-aza-13, 17- dioxabicyclo[14.1.0]heptadecan-5,9-dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-chloro-2- (2-methyl-4-thiazolyl) ethenyl) - 8,8-trimethylene-10, 12-dimethyl-4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fluor-2-(2-methyI-4- oxazolyl)ethenyl)-1-aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-Dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) -1- aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1. OJheptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1. OJheptadecan 5,9-dione (1 R,3S(Z),7S, 10R, 11 S, 12S,16R)-16-Chlor-7, 11 -dihydroxy-3-(1 -fluor-2-(2-methyl-4- oxazolyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-(1 R, 3S (Z), 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (1-fluoro-2- (2-methyl-4-oxazolyl) ethenyl ) -8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecanoic 5,9-dion5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-13-chlor-16-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-Dihydroxy-13-chloro-16- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) -1 - aza-10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8, 10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(1-fluor-2-(2-methyl-2- pyridyl)ethenyl)-8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (1-fluoro-2- (2-methyl-2-pyridyl) ethenyl) - 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S(Z))-4,8-Dihydroxy-7-ethyl-13-chlor-16-(1-chlor-2-(2-methyI-2- pyridyl)ethenyl)-1 -aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S (Z)) - 4,8-Dihydroxy-7-ethyl-13-chloro-16- (1-chloro-2- (2-methyl-2-pyridyl) ethenyl ) -1-Aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-ene-2,6-dione (1S,3S(Z),7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-7-ethyI-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8,12-trimethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan- 5,9-dion (1R,3S(Z),7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-7-ethyl-3-(1-chlor-2-(2- methyl-2-pyridyl)ethenyl)-8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo[14.1.OJheptadecan- 5,9-dion(1S, 3S (Z), 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2-pyridyl) ) ethenyl) -8,8,12-trimethyl-4-aza-13,17-dioxabicyclo [14.1.0jheptadecane-5,9-dione (1R, 3S (Z), 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-7-ethyl-3- (1-chloro-2- (2-methyl-2-pyridyl ) ethenyl) -8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo [14.1.OJheptadecan-5,9-dione (4S,7R,8S,9S,13E, 16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzothiazolyl)-1-aza- 10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4- aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan-5,9-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4- aza-13,17-dioxabicyclo [14.1.0Jheptadecan-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzothiazolyl)-1-aza- 10-oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetraamethyl cyclohexadec-dione-13-en-2,6- (4S,7R,8S,9S,13Z, 16S)-4,8-Dihydroxy-13-chlor-16-(2-methyI-5-benzothiazolyl)-1 -aza- 10-oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza- 10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (1S,3S,7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl-4 aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzothiazolyI)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzothiazolyI) - 8,8,10,12-tetramethyl-4 aza-13,17-dioxabicyclo [14.1.0Jheptadecan-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-ethyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1-aza-10-oxa-5,5,9-trimethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-ethyl-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza-10-oxa-5, 5,9-trimethyl-cyclohexadec-13-en-dione 2,6- (1 S,3S,7S,10R,11 S,12S,16S)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8,12-trimethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8,12- trimethyl-4-aza-13,17-dioxabicyclo [14.1.0Jheptadecan-5,9-dione (1R,3S,7S,10R,11S,12S,16R)-16-Chlor-7,11-dihydroxy-10-ethyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.OJheptadecan-5,9- dion (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-7-allyl-13-chlor-16-(2-methyl-5-benzothiazolyl)- 1 -aza-10-oxa-5,5,9-trimethyl-cycIohexadec-13-en-2,6-dion(1R, 3S, 7S, 10R, 11S, 12S, 16R) -16-chloro-7,11-dihydroxy-10-ethyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12-tetramethyl- 4-aza-13, 17-dioxabicyclo [14.1.Ojheptadecane-5,9-dione (4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-7-allyl-13-chloro-16- (2-methyl-5-benzothiazolyl) -1-aza-10-oxa-5, 5,9-trimethyl-cycIohexadec dione-13-en-2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyl)-8,8, 12-trimethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyl) -8,8, 12-trimethyl- 4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-10-allyl-3-(2-methyl-5- benzothiazolyI)-8,8,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9- dion(1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-10-allyl-3- (2-methyl-5-benzothiazolyI) -8,8,12- tetramethyl-4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1 -aza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1 -aza-10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-13-fluor-16-(2-methyl-5-benzoxazolyl)-1-aza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-fluoro-16- (2-methyl-5-benzoxazolyl) -1-aza-10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (1 S,3S,7S,10R,11 S,12S,16S)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4-aza-13, 17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 S, 3S, 7S, 10R, 11 S, 12S, 16S) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl- 4-aza-13, 17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (1 R,3S,7S,10R,11S,12S,16R)-16-Fluor-7,11-dihydroxy-3-(2-methyl-5-beiι zoxazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0]heptadecan-5,9-dion(1 R, 3S, 7S, 10R, 11S, 12S, 16R) -16-fluoro-7,11-dihydroxy-3- (2-methyl-5-beiι zoxazolyl) - 8,8,10,12-tetramethyl- 4-aza-13,17-dioxabicyclo [14.1.0] heptadecane-5,9-dione (4S,7R,8S,9S,13E,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1-aza-10- oxa-5,5,7,9-tetraamethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13E, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1-aza-10-oxa-5,5,7, 9-tetraamethyl cyclohexadec-dione-13-en-2,6- (4S,7R,8S,9S, 13Z,16S)-4,8-Dihydroxy-13-chlor-16-(2-methyl-5-benzoxazolyl)-1 -aza-10- oxa-5,5,7,9-tetramethyl-cyclohexadec-13-en-2,6-dion(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-dihydroxy-13-chloro-16- (2-methyl-5-benzoxazolyl) -1 -aza-10-oxa-5,5,7, 9-tetramethyl-cyclohexadec 13-ene-dione-2,6- (1S,3S,7S,10R,11S,12S,16S)-16-Chlor-7,11-dihydroxy-3-(2-methyl-5-benzoxazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan-5,9-dion(1S, 3S, 7S, 10R, 11S, 12S, 16S) -16-chloro-7,11-dihydroxy-3- (2-methyl-5-benzoxazolyl) - 8,8,10,12-tetramethyl-4- aza-13,17-dioxabicyclo [14.1.0Jheptadecan-5,9-dione (1 R,3S,7S, 10R, 11 S, 12S, 16R)-16-Chlor-7, 11 -dihydroxy-3-(2-methyl-5-benzothiazolyl)- 8,8,10,12-tetramethyl-4-aza-13,17-dioxabicyclo[14.1.0Jheptadecan-5,9-dion.(1 R, 3S, 7S, 10R, 11 S, 12S, 16R) -16-chloro-7, 11 -dihydroxy-3- (2-methyl-5-benzothiazolyl) - 8,8,10,12-tetramethyl- 4-aza-13,17-dioxabicyclo [14.1.0Jheptadecan-5,9-dione. 3. Pharmazeutische Präparate enthaltend mindestens ein Epothilon-Derivat der allgemeinen Formel I gemäß Anspruch 1 sowie einen pharmazeutisch verträglichen Träger. 3. Pharmaceutical preparations containing at least one epothilone derivative of the general formula I according to claim 1 and a pharmaceutically acceptable carrier. 4. Verwendung der Verbindungen der allgemeinen Formel I gemäß Anspruch 1 zur Herstellung von Arzneimitteln. 4. Use of the compounds of general formula I according to claim 1 for the manufacture of medicaments.
EP01927918A 2000-04-20 2001-04-19 9-oxa-epothilon derivatives, method for the production and use thereof in pharmaceutical preparations Withdrawn EP1282618A2 (en)

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DE10020899A DE10020899A1 (en) 2000-04-20 2000-04-20 New 9-oxa-epothilone derivatives, are phase-specific cell division regulators useful for treating malignant tumors, angiogenesis or inflammatory disease
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US6204388B1 (en) 1996-12-03 2001-03-20 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
AU756699B2 (en) 1996-12-03 2003-01-23 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6706931B2 (en) 2000-12-21 2004-03-16 Shell Oil Company Branched primary alcohol compositions and derivatives thereof
ATE476995T1 (en) * 2002-06-10 2010-08-15 Novartis Pharma Gmbh COMBINATIONS CONTAINING EPOTHILONES AND THEIR PHARMACEUTICAL USES
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
JP4791183B2 (en) 2002-08-23 2011-10-12 スローン−ケッタリング インスティトュート フォア キャンサー リサーチ Synthesis and use of epothilone, its intermediates and analogues
EP1559447A1 (en) 2004-01-30 2005-08-03 Institut National De La Sante Et De La Recherche Medicale (Inserm) Use of epothilones in the treatment of neuronal connectivity defects such as schizophrenia and autism

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US6605599B1 (en) * 1997-07-08 2003-08-12 Bristol-Myers Squibb Company Epothilone derivatives
DE19908765A1 (en) * 1999-02-18 2000-08-24 Schering Ag New, chemically and metabolically stable 16-halo or cyano-epothilone derivatives are cell division regulators useful e.g. for treating malignant tumors or chronic inflammatory disease
CA2361278A1 (en) * 1999-02-18 2000-08-24 Ulrich Klar 16-halogen-epothilone derivatives, method for producing them and their pharmaceutical use
PE20010116A1 (en) * 1999-04-30 2001-02-15 Schering Ag 6-ALKENYL-, 6-ALKINYL- AND 6-EPOXY-EPOTILONE DERIVATIVES, PROCEDURES FOR THEIR PREPARATION
DE19921086A1 (en) * 1999-04-30 2000-11-02 Schering Ag New stable 6-alkenyl- or 6-alkynyl-epothilone derivatives, are cell division regulators useful for treating malignant tumors, angiogenesis or chronic inflammatory disease

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