IE58359B1

IE58359B1 - New phenol derivatives, pharmaceutical compositions containing these compounds and processes for the preparation of these compounds and compositions

Info

Publication number: IE58359B1
Application number: IE74586A
Authority: IE
Original assignee: Gruenenthal Chemie
Priority date: 1985-05-23
Filing date: 1986-03-21
Publication date: 1993-09-08
Also published as: IT8620518A1; DK162794C; IE860745L; FI862072A; DK238686A; IT1188686B; FI82298C; DE3518644C2; FR2582418A1; FI862072A0; DE3518644A1; BE904792A; IT8620518A0; DK238686D0; FR2582418B1; DK162794B; FI82298B; NL8601310A

Abstract

In the case of a sanitary mixing fitting which is preferably electronically controlled, each of the valves for hot and cold water supply has an electromechanical actuating member. The ratio of the opening angle of the two valves is regulated in dependence on the measured actual temperature of the mixed water and of the pre-selected desired temperature. In this arrangement, the pre-selectable throughflow quantity of the mixed water is kept constant.

Description

Polyunsaturated higher fatty acids, such as e.g. arachidonic acid, serve in the metabolism of humans and of mammals as substrates for the enzymatically catalysed formation of physiologically important eicosanoids, such e.g. prostaglandins and leukotrienes, a class of substances which is also known by the name slow reacting substance of anaphylaxis' (SRS-A). Prostaglandin formation is catalysed here by cyclo-oxygenase (also called prostaglandin synthetase), and leukotriene formation by 5-1ipoxygenase.

Whereas prostaglandins display a number of desirable actions in the organism, it is known that leukotrienes or SRS-A are responsible for the 10 development of allergic reactions, bronchoconstrictions, inf laminations, asthma and a large number of other undesirable effects, it would therefore be desirable to be able to have available chemically and metabolical ly stable compounds which leave prostaglandin formation in the organism uninfluenced, but at the same time inhibit 5-lipoxygenase as selectively or specifically as possible and in this way prevent the formation of undesirable leukotrienes. It has now been found that certain phenol derivatives which carry an unsaturated 11-hydroxyalkyl radical in the 4position are sufficiently stable chemically and metabolicaIly for therapeutic use and have a specific inhibiting action against 520 lipoxygenase.

These new phenol derivatives correspond to the general formula in which A and B are identical or different and each represent one of the groups 25 -C=C-, cis-CH=CH~ or trans-CH=CH-, R-j denotes hydrogen or a straight-chain alkyl radical with 1 to 6 carbon atoms, or a 5 to 7-raembered cycloalkyl group, or a group of the formula ~CCH2)ra-0-Rp wherein n represents one of the ' numbers 1, 2 or 5 and R™ represents methyl or ethyl, or a group of the formula '8 wherein X represents a single bond, a 9rouP or e CH20- group end Rg denotes a hydrogen, chlorine or fluorine atom or a methyl, methoxy or trifluoromethyl group and n represents one of the numbers 1 or 2, R-, represents hydrogen, methyl or ethyl, R~ denotes hydrogen or an acetyl or propionyl radical, Rz represents hydrogen, an acetyl or propionyl radical or a straight-chain or branched alkyl radical Rp with 1 to 4 carbon atoms, Rbj represents a group of the formula -COOR-jq, wherein R-jq is a hydrogen atom, a pharmaceutically tolerated cation, in particular a monovalent cation, a straight-chain or branched alkyl radical with 1 to ό catbon atoms or the group -(CHg^-N-CCCHjpp-CHTjZ^, which p represents zero or one of the numbers 1 to 5, and of (sic) pharmaceutically tolerated salts of these basic esters with acids, or represents a group of the formula /Rn . -CO-N *12 I i wherein R^ and are identical or different and represent hydrogen, the alkyl radical Rq or 2-hydroxyethyl, or one of these radicals denotes a hydroxyl group and the other denotes hydrogen, or R.jand R^ taken together represent the group -(CH2)q-> which q represents one of the numbers 4, 5 or 6, or represents a group of the formula •CQ-H OR wherein R^- represents hydrogen, -(CHgJp-CHg, carboxymethyl, acetyl or propionyl and p in each case has the same meaning as above, or represents a group of the formula -CO"NH'’(CHp5r~N(CH2)2i' wherein r represents one of the numbers 2 or 3, or pharmaceutically tolerated salts thereof with acids, or represents a group of the formula in which V denotes an oxygen atom or the group or if appropriate pharmaceutically tolerated salts thereof with acids, or represents a nitrile radical, or represents a hydroxyl, acetoxy or propionyloxy group, an alkoxy group ORg or - taken together with 0R^ - represents the methylenedioxy group and R^ represents hydrogen, a hydroxyl, acetoxy or propionyloxy group, the alkyl radical R^ or an alkoxy group OR^, wherein R^ in each case has the same meaning as above» If R.j and R? do not have the same meaning, a centre of asymmetry occurs on 20 the carbon atom carrying these radicals. In these cases, the invention relates both to the racemates and to the optically active forms of the compounds of the formula IIn preferred compounds of the formula 3, the groups A and B each have the same meaning and represent, in particular, ~C=C- or eis-CH^CH-. If A and 8 represent different groups, B preferably denots -C=C~.

R^ preferably represents a hydrogen atom., These preferred groups of compounds of the formula I can be represented by the following structural formulae: 1) If A and B represent the group -C=C~ R, '6 2) If A and B represent the group -cis"CH=CH- OH '6 3) If A and B are different and B represents the group ~C=C R.

R, '5 OH wherein, in each case, R.j to Rg, Rg, R^ and A have the same meaning as above» In particularly preferred compounds of the formula I or compounds of the formulae I’, I' and I’*, Rg and R- represent hydrogen,, whereas in these compounds R^ preferably denotes hydrogen,, a straight-chain alkyl radical with 1 to 6 carbon atoms or a phenyl or cyclohexyl radical/R11 Preferred meanings of Re are the groups -CQ-N -CO-H WP~CH3 /~~\ , -CO-N V , 0Rq OR wherein R^, Rp, R^ and Y represent the same radicals represents methyl and represents as above, wherein Rq in particular hydrogen) and the hydroxyl group.

As already mentioned above,, the compounds of the formula I have a specific inhibiting action against 5-lipoxygenase, which has been determined by in vitro experiments.

To determine the 5-Lipoxygenase inhibition, basophilic Leukaemic leucocytes from the rat were cultured in vitro and, when a cell density of about 10^ cells per ml was reached, were centrifuged off from the nutrient medium at 400 g. The residue was suspended in 50 mM potassium phosphate buffer of pH 7-4 so that the cell count was 1.5 x 10? cells per mlIndomethacin (10 pM) and calcium chloride (2mM) were added to 1 ml portions of this suspension and the portions were incubated in the presence or absence of one of the test substances with radi©actively labelled arachidonic acid and the calcium ionophor A 23 187 at room temperature for 5 minutes. After acidification to pH 5, the arachidonic acid metabolites formed under the influence of the 5-lipoxygenase were extracted with ethyl acetate and separated by thin layer chromatography using a mobile phase mixture suitable for the leukotrienes Cc.f. jakschik et al- BiochemBiophys. Res. Commun. 102, 624 ¢1981)3- The distribution of the radioactivity amongst the various metabolites was measured with the aid of a thin layer scanner. If the percentage amounts of 6-lipoxygenase products formed (5-HETE and LTB^) are related to the amount or concentration of the total radioactivity employed or the test substance of the formula I, the ’’IC^g value I (i.e. the concentration which effects SOX inhibition of the -lipoxygenase) can be determined.

The influence of the compounds of the formula I on cyclooxygenase activity was investigated with the aid of sheep seminal vesicle microsones suspended in potassium phosphate buffer (50 mH, pH 7-5) by incubation with the test substance and ^C-labelled arachidonic acid for 10 minutes at room temperature. After addition of glacial acetic acid, the mixture was extracted with ethyl acetate and the concentrated extract was separated on silica gel thin layer plates using ether/hexane/glacial acetic acid (50:50:1). The distribution of the radioactivity amongst the prostaglandins formed and the unchanged arachidonic acid were determined and the "ICgg value II" (for 50% inhibition of the cyclooxygenase) was determined therefrom for the particular substance.

Thus, for example, for the products of the examples mentioned in the following table, the particular IC^g values quoted were found, from which IC5qix the quotient -- can be calculated.

Example ICggCptl] for inhibition of Quotient 5-lipoxygenase (I) cyclooxygenase (II) 7 0.15 38 253.3 9 0.31 28 90.3 13 0.35 31 88.6 14 0.21 25 119.1 15 0.32 >100 >320.0 16 0.28 37 132.1 18 0.1 38 380.0 22c 2.9 130 44.8 22d 2.8 180 04.3 This table shows that the IC^q values for the cyclooxygenase inhibition are usually more than 50 times higher than the values for the 5-lipoxygenase inhibition, i.e. that the test substances very specifically cause only inhibition of the 5-lipoxygenase activity.

On the basis of this favourable influence on the metabolization of polyunsaturated fatty acids, in particular inhibiting action on the formation of arachidonic acid metabolites of 5-lipoxygenase, such as 5hydroxyperoxyeicosatetraenoi c acid (5-HPETE), 5-hydroxyei cosatetraenoi c acid (5-HETE) and SRS-A, the compounds of the formula I according to the invention cause numerous physiologically useful effects in the organism of humans and mammals, such as e.g. antiallergic, antianaphylactic, antiinflammatory, antiasthmatic, antihypertensive and circulation-promoting (coronary and cerebral circulation) actions, reduction in leucocyte aggregation and the formation of leucocyte thrombi etc.

These therapeutically useful properties can be demonstrated, for example, by the following results obtained in animal experiments: An oedema is induced in Sprague-Dawley rats by subplantar injection of 0.1 ml of a kaolin suspension (100 mg/l) and the paw volume is measured hourly by plethysmoraetry.

Three hours after inducement of the oedema, the particular test substance, suspended in 5 ml IX sodium carboxymethylcellulose solution per kg body weight of the experimental animals, is administered intraperitoneally. The change in paw volume by oedema inhibition under the action of the substance in comparison with the volume measured immediately before administration of the substance can be seen from the following table (values above 100% indicate a decrease in the oedema volume to below the starting value): S· Product of example Oose (mg/kg) X Inhibition maximum value Time after administration of substance (hours) 7 46.4 65 1 100,.0 164 1 14 46.4 68 1 100.0 127 2 15 100.0 73 2 16 100.0 54 1 If the administration of the test substance takes place at the same time as the kaolin administration by injection of 1 mg substance per paw, dissolved in 0.1 ml 1% sodium carboxymethylcellulose solution, the following maximum values of c •edema inhibition or formation of the oedema are measured: Product of X Inhibition Time after example (maximum valu e) administration of substance (hours) 7 36 2 5 61 3 14 46 2 15 64 5 16 ζ ς 7 This table also shows (c.f. in particular the maximum values of the action observed after 5 and 7 hours for the products of examples 15 and 16) that Ο the compounds of the formula I according to the invention are quite stable towards metabolic breakdown and therefore remain active for a long period of time.

On the basis of these useful properties in respect of stability and action, the compounds of the formula I are suitable e.g. as anti a Ilergics, antianaphylactics, anti-inflammatories, antiasthmatics, antihypertensives, antithrombotic agents, agents for the prophylaxis or therapy of ischaemic cardiac infarction, disturbances in the coronary and/or cerebral arteries etc.

The compounds according to the invention have only a low toxicity, which manifests itself only at dosages which are far higher than those to be used therapeutically or prophylactically. They can therefore be administered as such in suitable pharmaceutical formulations to humans or animals.

The invention accordingly also relates to medicaments which contain one or more of the compounds of the formula I according to the invention as the active compound. The amount of active compound to be administered to the patient varies according to e.g. the weight of the patient, the administration route, the indication and the severity of the illness. Taking into account these factors, the active compound content per individual dose is in general about 0.01 - 50 mg, and in particular in formulation forms for parenteral administration 0.01 to 10 mg, and in formulations for oral or rectal administration about 0.1 to 50 mg.

Medicaments for parenteral administration can be either solutions or suspensions, and dry formulations which are easy to reconstitute are also possible.

Sprays for intranasal or oral administration or for administration of the substances via the bronchi are also particularly suitable administration forms.

Formulation forms of the compounds of the formula I for oral use, such as tablets, coated tablets, capsules, granules, drops and elixirs or syrups, and also suppositories and percutaneous administration formulations (such as e.g. plasters or the like containing the active compounds in a depot in dissolved form, if appropriate with addition of agents which promote penetration of the skin) are also advantageously suitable for many prophylactic or therapeutic uses. These formulation forms for oral, rectal or percutaneous use are advantageously prepared such that the active compound is released therefrom in a delayed manner, in order thus to guarantee a uniform supply of the active compound to the patient over a prolonged period of time (for example 24 hours).

All the abovementioned pharmaceutical formulation forms are known per se, and since the compounds of the formula I according to the invention are quite stable chemically, their incorporation into these formulation forms presents no problems at all to the expert. The usual care in selection of auxiliaries, such as carrier materials, dyestuffs, flavour correctants, binders, tablet disintegrating agents etc., must of course be taken in this preparation according to the invention of these medicaments, and in particular in the preparation of formulation forms for parenteral use, sterility and - if they are in liquid form - isotonicity should be ensured.

The preparation according to the invention of the compounds of the formula I can be carried out by a procedure in which A) a compound of the general formula II in which A, B, end R? have the same meaning es in formula I, R^, represents the alkyl radical Rq or a protective group which can be split off under mild conditions, such as a tetrahydropyran-2-yl radical or in particular a tert-butyIdimethyl or -diphenylsi lyl group, represents the group 0R^ or has the same meaning as R^, with the proviso that in this radical R^q cannot represent a cation and the basic groups which may be present in R^ cannot be in salt form, or R.^, taken together with the group OR-jz, represents a methyLenedioxy group, R^ denotes a hydrogen atom or one of the groups R^ θ^14 anc^ ^17 a Protective group which can be split off under mild conditions (such as e.g. one of those mentioned in the definition of R-j^/· 1) is prepared by reaction of a compound of the formula ?2 R, — C~C = C~ Ms i 3 0Rn wherein R-j, Rg and R^y have the same meaning as above and He represents a lithium, sodium or potassium atom or one of the radicals -HgBr or -Mgl, with a compound of the formula in which B and R^ to R-,^ have the same meaning as above and R-j θ represents a bromine or an iodine atom, if appropriate in the presence of catalytic amounts of copper(I) halides, copper(I) cyanide or other copper salts. Inert solvents, such as aliphatic hydrocarbons or, preferably, anhydrous ethers, such as diethyl or diisopropyl ether, tetrahydrofuran, dioxane etc», are ar used as the solvent. If Me represents a lithium atom in particular, a solution of the compound of the formula IV in hexamethylphosphoric acid triamide, 1,3-di methyl-tetrahydro-2-(1H)-pyrimidinone, 1,3dimethyl-Z-imidazolidinone or e.g. in Ν,Μ,Μ',Ν'-tetraethyIsulphamide or appropriately dipolar aprotic cosolvents is advantageously slowly added to a solution of the compound of the formula HI in one of the solvents mentioned. Λ] ο 1 The reaction is carried out at temperatures of about -80° to +75°C, and preferably, if Re is a lithium, sodium or potassium atom, at -80° to 0°C, and if Re denotes a radical -MgBr or at -5° to *25°C.

If the radical R^ represents the group OR^z, in particular, the addition of polar cosolvents can be dispensed with and the reaction can be carried out at a higher temperature, such as e.g. at the boiling point of the solvent used., 2) If the radical R^ in the compound of the formula IV represents the group OR-./, the preparation of the compound of the formula II can also be effected by reaction thereof with a compound of the formula .2 R c = C — Me Ilia wherein R^, R, and R-j? have the same meaning as above and Re* represents a lithium, sodium or potassium atom, in liquid ammonia. 3) The compound of the formula II can also be obtained by a process in which a compound of the formula R, OR in which A, R^, R„ R^~ and R^g have the same meaning as above. is reacted with a compound of the formula Me" wherein to R-j6 have the same meaning as above and Me represents one of the groups Me or Me* defined above. under the conditions mentioned above for 1 and 2. 4) Compounds of the formula IX in which A represents ~CH=CH- can also be obtained by a process in which a strong anhydrous base, such as nbutyllithium, potassium tert-butylate or e.g. sodium bis-Ctrimethylsi lyDamide, is allowed to act on a compound of the formula VII in which R-j, Rg and R,jj have the same meaning as above and represents a chlorine, bromine or iodine atom, in the presence of solvents, such as tetrahydrofuran, n-hexane, benzene or dimethylformamide, if appropriate with addition of hexamethylphosphoric acid triamide or e.g. dimethylsulfoxide, the corresponding phosphorane being formed, with HR-jg being split off, and the product then giving the compound of the formula IX in question by reaction with an aldehyde of the formula VIH wherein B and R.jz to R^ have the same meaning as above. at temperatures of about -80° to +30°C.

The same product is also accessible by reaction of the phosphorane formed by analogous action of a base on the compound of the formula wherein B, R^^ to R.^ and R-(p have the same meaning as above, with an aldehyde of the formula R? .0 |2 / R,-C~C^ ί ! \ OR,7 H wherein R^, R? and R«y have the same meaning as above.

) Analogously to the procedure described above for A,4), compounds of the formula II in which B represents -CH=CH- are obtained by reaction of a phosphorane formed from a compound of the formula ?2 c(ch2)7 P(CJ-L),~R OR wherein A, R^, R5, and R^p have the same meaning as above by the action of a base, with an aldehyde of the formula ΧΠ or by reaction of the phosphorane obtained by the action of a base on the compound of the formula '19 ^C6H5^3P XIII wherein R^ to R^ and R^ have the same meaning as above with an aldehyde of the formula J in which A, R^, R5 and R^ have the same meaning as above under the conditions mentioned for A4.

The protective groups contained in R^/ to R^y are then split off from the resulting compound of the formula II in a manner which is known per se, which can also be effected selectively because of the various possible methods for splitting off. Thus, a tetrahydropyran-Z-yl group can preferably be split off in methanolic or ethanolic solution at about 50° - 60°C by addition of catalytic amounts of pyridinium toluene-4~ sulphonate. If e.g. the tert-butyIdimethyl or -diphenylsilyl group are present ars protective groups, this group can preferably be split off by the action of tetra-n-butylammonium fluoride in an inert solvent, such as tetrahydrofuran, dioxan®, diethyl ether, methylene chloride etc., or of hydrogen chloride, dissolved in methanol, on the compound of the formula II at room temperature.

If at least one of the radicals Rg or R/ is to represent acetyl or propionyl or at least one of the radicals Rg and R^ is to represent acetoxy or propionyloxy, the acid radical in question is then introduced in the customary manner, for example by treatment with a solution of acetic or propionic anhydride in pyridine or by reaction of acetyl or propionyl chloride in the presence of an acid-binding agent. 8) In a preferred process for the preparation of compounds of the formula I, a compound of the formula 7 - C = CH XV wherein A, R^ and Rg have the same meaning as above and Rgg represents a hydrogen atom or has the same meaning as Rp is reacted in the presence of a secondary or tertiary amine which is liquid at about -10° to +80°C, in particular a dialkyl™ or trialkylamine with 2 or 3 carbon atoms in each of the alkyl radicals, pyrrolidine or piperidine, with the addition of catalytic amounts (by these there to be understood amounts of about 0.01 to 1 per cent per mol compound of the formula XV employed) of a complex palladium catalyst, in particular bis(triphenylphosphine)palladium(II) chloride or acetate or tetrakis(triphenylphosphine)-palladium, and if appropriate with the addition of catalytic amounts of copper(I) iodide at about 0° to 75°C, with a compound of the formula '22 XVI wherein R^g has the same meaning as above, Rg-j denotes a hydrogen atom, an alkyl radical Rq or a protective group which can be split off under mild conditions (such as e.g. one of those mentioned for R^), Rgg represents the group ORg? or has the same meaning as Rg, with the proviso that in this radical R..Q cannot represent a cation and the basic groups which may be present in Rg cannot be in salt form, or Rgg, taken together with the group ORg-j, represents a methylenedioxy group and Rgg has the same meaning as R^ or represents a hydroxyl group.

A compound of the formula R, R.

OR R XVII is thus obtained, from which the protective groups contained, if appropriate, in Rjq to ^23 ere SP^1- °^τ in the manner described for the conversion of the compound of the formula II into the compound of the formula I, it also being possible for this to be carried out selectively here, if appropriate. If at least one of the radicals Rj or R^ is to represent the acetyl or propionyl radical or at least one of the radicals R«j and R^ is to represent the acetoxy or propionyloxy radical, this radical is then introduced in the customary manner, for example as described above for A).

C) Compounds of the formula I can furthermore also be obtained by a process in which a compound of the formula Me — CSC— (CH2)5 XVII wherein Me, B and R,jz to R^ have the same meaning as above, are reacted with a compound of the formula R2 XIX in which and R2 have the same meaning as above in the presence of sn inert solvent, such as tetrahydrofuran, diethyl ether or e.g. n-hexane, st about -80° to +3Q°C, to give a compound of the formula wherein A, B, Rp R? and R^z to R^ have the same meaning as above and the protective groups contained, if appropriate, in R^4 to R^ are split off in the manner described above. If at least one of the radicals R- and or Rj and R^ in the compound of the formula I is to represent or contain an acetyl or propionyl radical, this is then introduced in the customary manner.

D) To prepare compounds of the formula I in which R^ is other than hydrogen, a procedure can be followed in which a compound of the formula XXI in which A, 8 and R^ to R^ have the same meaning as above and Rj has the same meaning as R«, with the exception of hydrogen, is first prepared by a process in which Da compound of the formula icH3(CH2)p"032 E " CH2 ~ ~ R1 XXH 0 wherein p and Rj have the same meaning as above, p preferably representing zero, is treated with an anhydrous base, such as sodium hydride or nbutyllithium, in an inert solvent, such tetrahydrofuran, di methoxyethane, n-hexane or toluene, and the product is then reacted with a compound of the formula VIII at temperatures of about -1Q°C to +35°C, preferably 0°C to 10°C, or 2) a compound of the formula in which B and to R^ have the same meaning as above, is reacted with a compound of the formula R19-S~Ri XOT wherein R^ and R,jq have the same meaning as above in the presence of a tertiary amine which boils above about +8Q°C, in particular a trialkylamine with 2 or 3 carbon atoms in each of the alkyl radicals, under the conditions described in 8 for the reaction between the compounds of the formula XV and XVI.

The corresponding compound of the formula I Cin which R-j and if appropriate Rg cannot represent hydrogen) is then obtained from the compound of the formula XXI prepared by this route by reduction or by reaction with a compound of the formula R^-Me, wherein Me has the same meaning as above and R^iasthe same meaning as Rg, with the exception of hydrogen, subsequent splitting off of protective groups present in R^ to and if appropriate - if at least one of the radicals Rg and R^ or Rg and R^ is to represent or contain an acetyl or propionyl radical ~ acylation, which can be carried out before or after the protective groups are split off from R^ - R1620 The reduction of the compound of the formula XXI is carried out with metal borohydrides, such as zinc borohydride or in particular sodium borohydride, preferably with addition of cerium(III) chloride, in methanol, ethanol or di methoxyethane, with addition of water, at temperatures of about -20° to +30°C, preferably at about +20°C. 1 If desired, triple bonds (in A, and/or 0) present in the compounds of the formula I obtained according to A, B, C or D can be hydrogenated to double bonds. This hydrogenation is in general carried out with catalytically excited hydrogen under normal pressure at room temperature using, in particular, palladium catalysts, preferably Lindlar catalysts, such as e.g. palladium poisoned with lead on calcium carbonate. Solvents which are used here in a manner which is known per se are e.g. n-hexane, methanol, ethanol, ethyl acetate, benzene, toluene and diisopropyl ether, advantageous ly with addition of 0.1 - 2% quinoline or pyridine, or pure pyridine.

If the radical Rg in the compound of the formula I obtained represents the group COOR-jq, wherein R-jq is the alkyl radical Rq or the group ~(CH2)2~NE(CH2)p-C:H~Zi2, this ester grouping can subsequently also be hydrolysed in a manner which is known per se, e.g. to the free acid (if appropriate followed by salt formation by neutralization with a base which is tolerated pharmaceutically in salt form, such as e.g. dilute sodium hydroxide solution or potassium hydroxide solution), these esters being treated with an aqueous solution of e.g. sodium hydroxide, potassium hydroxide or lithium hydroxide, advantageously at room temperature in the presende of a water-miscible solvent, such as methanol, ethanol or tetrahydrofuran.

On the other hand, the corresponding amides or hydroxamic acids can be obtained from the esters initially obtained by reaction with amines of the the formulae /R11 ΗΝχ s H2N-(cH2)r-N(CH3)2 orR12 wherein r and Y have the same meaning as above, or with hydroxylamine derivatives of the formula ' /(CH2!p * ™3 HN wherein p and R^ ^ave ^e same meaning as above, these products on the other hand of course also being accessible in a manner which is known per se from the free carboxylic acids (R^ = COOH), with the aid of dehydrating agents, such as dicyclohexylcarbodiimide, dimethylformamide/thionyl chloride and the like, or by intermediate formation of reactive functional derivatives of the carboxylic acid radical, such as e.g. mixed anhydrides, acid halides etc.

If the radical Rg in a compound of the formula ϊ obtained by one of the above routes contains a basic group, this can easily be converted by neutralization with a suitable acid in a manner which is known per se into a pharmaceutically tolerated salt with this acid. If this salt formation has taken place in a solvent in which the salt formed is soluble, this is advantageously isolated by freeze-drying, although precipitation by addition of suitable liquids which are miscible with the solvent and in which the salt is insoluble can of course also be used to isolate the salt. Preferably, however, the free base is dissolved in an anhydrous agent of low polarity, such as e.g. diethyl ether, an ethereal solution of the acid is added and if appropriate n-hexane or petroleum ether, for example, is added in order to start the crystallization. On the other hand, in this case also isolation of the salt by evaporation, preferably in vacuo, is of course possible. Suitable acids for this salt formation are e.g. hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, formic acid, acetic acid, benzoic acid, salicylic acid, benzenesulphonic acid and other acids customary for the preparation of pharmaceutically usable salts.

Other conversion possibilities for the radical R^ are obvious to the expert. For example, the free carboxyl groups can easily be converted into the carboxymethyl or carboxyethyl group by treatment with diazomethane or diazoethane (especially if R~ and are other than hydrogen and R^ does 3 not represent a hydroxyl group).

In the synthesis processes described in the context of this Application, in each case those starting materials in which any double bonds present are already in the configuration desired in the end product are advantageously used. Isomer resolution in cases where a further double bond is introduced in the last stage but is not obtained with a uniform configuration is in this way facilitated. The isomer resolution can be carried out in a manner which is known per se, e.g. by column chromatography.

If R-j and R2 differ from one another, any racemate resolution desired can be carried out in the customary manner. E.g. if Rg contains a basic group or represents a free carboxyl group, this can be achieved by salt formation with optically active acids or bases in a manner which is known per se.

The starting compounds for the procedures described above for the preparation of the compounds of the formula I are in all cases prepared in a manner which is known per se. The routes to be considered for these are chosen, in particular, by also taking into account the various meanings of A and B.

I E.g. the compounds of the formula VI and from these those of the formula IV can be obtained by a procedure in which ch loromethy lenetriphenyl-phosphorane (produced in situ from chloromethyItriphenylphosphonium chloride by the action of e.g. n-butyllithium/dimethyIsulphoxide in tetrahydrofuran) is allowed to act on an aldehyde of the formula XII and hydrogen chloride is then split off from the compound formed, e.g. with η-butyllithium. The resulting phenylacetylene derivative is then converted into the compound of the formula VI by reaction e.g. with butyllithium, sodium hydride, potasium hydride or ethylmagnesium bromide or iodide. Reaction thereof with 1,6-dibromoor 1,6-diiodohexane, e.g. in diethyl ether or tetrahydrofuran, preferably in the presence of an aprotic dipolar solvent, at about 80°C and later at 0°C, then gives the compound of the formula IV.

II A compound of the formula V in which A represents -C = C- is obtained 4 e.g. by reaction of a compound of the formula III with 1,ό-dibromo- or 1,6-di1odo-hexane under the conditions described above in I for the reaction of the compound of the formula VI with one of these halogen compounds.

III The compound of the formula VIII is obtained by reaction of a compound of the formula VI with a compound of the formula XXV under the conditions described above in I, splitting off of the tetrahydropyran-2-yl group and oxidation of the resulting alcohol of the formula XXVI with e.g. pyridinium chlorochromate in methylene chloride.

If the hydroxyl group in the compound of the formula XXVI is replaced by a bromine atom, e.g. by reaction with carbon tetrabromide in the presence of triphenylphosphine, and the product is then reacted with triphenylphosphine (for exammple by boiling in acetonitrile under reflux for 12 to 24 hours), a compound of the formula IX in which represents bromine is obtained.

IV If a compound of the formula III is reacted with 1,7-dibromoheptane under th6 conditions mentioned in I and the resulting compound of the formula ft — h c 0R17 C — (CH2)7— Br XXVII is treated with triphenylphosphine Ce.g. heating in acetonitrile), the corresponding compound of the formula XI in which represents bromine is obtained.

V To prepare a compound of the formula XIV in which A represents -C=C-, a compound of the formula III in which R^g should not represent the tetrahydropyran-2-yI group is first reacted with a compound of the formula XXV under the conditions described in I and the tetrahydropyran-2-yl group is split off, an alcohol of the formula ?2 — C-C s C ™ (CH9)6 - CH2 — OH XXVIII ' ' ®17 being obtained. On oxidation (e.g. with pyridinium dichromate in dimethylformamide or methylene chloride), this gives the compound of the formula XIV.

VI A compound of the formula XV in which A represents -C=C" and R>g represents hydrogen can be obtained by reaction of a compound of the formula HC s c - (CH?)g C = C - Me XXIX with a compound of the formula XIX in anhydrous ethers, such as tetrahydrofuran, at temperatures of about -80°C to +65°C., VII To prepare compounds of the formula XVIII, the aldehyde of the formula* 20 VIII is used as the starting substance and the desired compound of the formula XVIII is obtained therefrom by reaction with chloromethylenetriphenylphosphorane, followed by splitting off of hydrogen chloride from the resulting product in accordance with the method described in I and subsequent reatment of the resulting compound of the formula XXIII with butyllithium, sodium hydride, potassium hydride or e.g. ethylmagnesium bromide or iodide.

The compound of the formula XXIII is also accessible on the other hand from the compound of the formula IV by reaction with lithium acetylideethylenediamine complex in dimethylsulphoxide or dimethylformamide at about 5° to 25°C.

Other routes for the preparation of starting compounds for the process according to the invention are obvious to the expert. Moreover, the starting materials are in some case also known from the literature or commercially available.

The following examples further illustrate the process according to the invention and the preparation of new starting materials and intermediate products. In carrying them out, no emphasis has been placed on achieving maximum yields. All the temperature data are uncorrected.

The products are in the fora of oils, unless other data is given in an individual case.

The ^H-NMR spectra were recorded at 60 RHz. The chemical shift of the spectroscopic resonance data was measured in ppm.

The n-butyllithium solution used in the examples contained - dissolved in n-hexane - 1.6 mol n-butyllithium/litre. However, it is of course also possible to employ solutions of other concentrations and/or with solvents other than n-hexane.

Unless stated otherwise, the ether used in the examples is diethyl ether, and the petroleum ether is that with a boiling range of 50° - 70°C.

For the chromatography and column chromatography - unless mentioned otherwise - silica gel 60 (0.040 - 0.063 mm) from Machery-Magel was used as as the stationary phase. For the HPLC, a silica gel marketed by the same company under the name Mucleosil C 18 (10 pm) was employed as the stationary phase.

Monitoring of the course of the reaction by thin layer chromatography was performed with ’’HPTLC pre-coated plates, silica gel 60 F 254" from E.

Merck, Darmstadt. The mobile phase used is stated in the examples in each case by "’(TLC: ...)".

The mixing ratios of the mobile phases for all the chromatographic analyses are always stated in volume/volume.

Enantiomer mixtures obtained in the examples were not separated - unless mentioned otherwise. In such cases, the data quoted thus relate to the enantiomer mixtures. 1θ Example 1 1-(4,-Hydroxy-5*-methoxycarbonylphenyI)-11-hydroxy-undeca-1,9-di ine a) Undeca--2,10-di in-l-pl 59.4 ml n-butyllithium solution are added dropwise to 13.42 g deca-1,9diine in 300 ml absolute tetrahydrofuran at -40°C in the course of one hour, while stirring and passing over dry nitrogen. The mixture is subsequently stirred for one hour, during which the temperature is allowed to rise to 0°C, ©»0 g paraformaldehyde are then added and the mixture is heated under reflux. (TLC: petroleum ether/ether - 3:2). After the end of the reaction, the mixture is broken down with saturated ammonium chloride solution and extracted several times with ether, and the extract is dried over sodium sulphate and evaporated in vacuo. Column chromatography of the residue with petroleum ether/ether (3:2) gives 8.27 g title compound as a liquid which gradually solidifies in a refrigerator.

(CDCl5): 1.2 - 1.80 (m, 9 H); 1.85 - 2.00 (t, 1 H); 2.00 - 2.40 (m, 4 H); 4.10 - 4.30 (t, 2 H). 8 b) 1-(4'-Hydroxy-38methoxycarbonyIphenyI)-11-hydroxy-undeca-1,9-diine 1.15 g product from example 1a and 1.95 g methyl 5-iodosalicylate are dissolved in 8 ml triethylamine which has been distilled over potassium hydroxide, and 0.066 g copper(I) iodide and 0.146 g bis-(triphenyl5 phosphine)-palladium(II) chloride are added, while stirring. (TLC: petroleum ether/ether - 1:1) when the reaction has ended, the mixture is diluted with ether and filtered and the filtrate is evaporated in vacuo» Column chromatogrhy of the residue with n-hexane/ethyI acetate (3:2) gives 1.54 g title compound as an oil which slowly solidifies to white crystals in a refrigerator. 1H-NMR (CDClg): 1.30 - 1.93 (m, 8 H); 2.05 - 2.60 (m, 4 H); 3,93 (s, 3 H); 4.06 - 4.33 (m, 2 H); 6.67 - 7.93 (m, 3 H) Example 2 1-(3‘-Carboxy-4'-hydroxyphenyl)-11-hydroxy-undeca-1,9-diine 3.24 ml of an aqueous solution of lithium hydroxide (1 mol/L) are added to 0.20 g product from example 1, dissolved in 2 ml methanol and 2 ml tetrahydrofuran. (TLC: petroleum ether/ether/glacial acetic acid : 3:6:0.1). After 20 hours, the mixture is evaporated in vacuo, the residue is diluted with 3 ml water and the mixture is acidified to pH 3 with hydrochloric acid, while cooling with ice-water. It is extracted three times with ether, washed with water, dried with sodium sulphate and evaporated, 0.172 g title compound being obtained. 1H-NMR (CDClg): 1,07 - 1.93 (m, 8 H); 2.00 - 2.70 (m, 4 H); 3.97 - 4.30 (m, 2 H); 6.63 - 7.93 (m, 3 H).

Example 3 1-(3'-Carbamoy1-4-hydroxyphenyI)-11-hydroxy-undeca-1,9-diine 0.180 g ester obtained obtained in example 1 are dissolved in 5 ml of a 9 methanolic solution of ammoinia (11% ΝΗ~). (TLC: petroleum ether/ether/ glacial acetic acid - 3:6:0.1). When the reaction has ended, the mixture is evaporated in vacuo. Column chromatography of the residue with petroleum ether/ether/glacial acetic acid (3:6:0.1) gives 0.132 g title compound in the form of white crystals. 1H-NMR (CDCl3): 1.07 - 1.97 (m, 8 H); 2.01 - 2.67 (ra, 4 H); 3.90 ~ 4.23 (m, 2 H); 6.56 - 7.77 (m, 3 H).

Example 4 1-(4,-Acetoxy-3,~raethoxycarbonylphenyl)-11-acetoxy-undeca-"1,9-diine 0.10 g ester obtained in example 1 are dissolved in 1 ml absolute tetrahydrofuran and 0.255 ml absolute pyridine, and 0.268 ml acetic anhydride is added dropwise, while cooling with ice-water. The mixture is allowed to warm to room temperature and, after 20 hours, is evaporated in vacuo. Column chromatography of the residue with petroleum ether/ethyl acetate G:2) gives 0.120 g title compound. 1H-NMR (CDC13): 1.20 - 1.93 (m, 8H); 1.97 - 2-70 (m, 4 H); 2.10 (s, 3 H); 2.33 (s, 3 H); 3.87 (s, 3 H); 4.47 - 4.73 (m, 2 H); 6.80 - 8.03 (m, 3 H).

Example 5 11-Hydroxy-1-(48-hydroxy-3,-methoxyphenyl)-undeca-1,9-diine) a) 3-Hethoxy-4"(tetrahydropyran-2il-yloxy)-benzaldehyde 0.20 g p-toluenesulphonic acid monohydrate is added in 3 portions to a solution of 20 g vanillin and 14.28 ml 3,4-dihydro-2H-pyran in 320 ml methylene chloride. After 60 minutes, 3 g anhydrous potasssium carbonate are added to the reaction mixture, the mixture is stirred in an ice-water bath for 30 minutes and 20 ml water are then added. The methylene chloride phase is washed twice with saturated sodium chloride Ο solution, dried over sodium sulphate and evaporated. The crude product is purified by column chromatography with petroleum ether/ether (2:1). 22.26 g title compound are obtained as an oil, which gradually solidifes to white crystals, which melt at 43°C, in a refrigerator. 1H-NMR (CDC13): 1.33 - 2.27 (m, ό H); 3.27 - 4.10 (m, 2 H); 3.90 (s, 3 H); .30 - 5.56 (m, 1 H); 7.02 - 7.43 (m, 3 Si); 9.70 (s, 1 H). b) 4(2‘~Chlorovinyl)-2-niethoxy~1~(tetrahydropyran-2,-yloxy)-benzene 6.48 g potassium tert-butylate are added in portions to a suspension of 20 g chloromethyl-triphenylphosphonium chloride in 70 ml absolute tetrahydrofuran at 20°C, while stirring and pasing over dry nitrogen. After stirring for 30 minutes, a solution of 9.01 g product from example 5a in 15 ml absolute tetrahydrofuran is added dropwise in the course of 15 minutes, and after a further 30 minutes the mixture is diluted with ethyl acetate. Xt is then washed in each case once with saturated solutions of sodium bicarbonate and sodium chloride, dried over sodium sulphate and evaporated. Column chromatography of the crude product with petroleum ether/ether (2:1) gives 8.22 g title compound.

^H-NMR (Ct)Cl3): 1.33 - 2.30 (m, ό H); 3.30 - 4.27 (m, 2 H); 3.87 - 3.90 (s,s 3 H); .20 - 5.50 (m, 1 H); 5.95 - 7.43 (m, 5 H). c) 3-Methoxy4-(tetrahydropyran-2tl-yloxy)-phenylacetylene .47 g product obtained in example 5b are dissolved in 28 ml absolute tetrahydrofuran, and 27.8 ml n-butyllithium solution are added dropwise at 0°C. The mixture is stirred at 0°C for a further 3 hours and then broken down with saturated ammonium chloride solution and extracted with ether. The extract is washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated. Column chromatography of the residue with petroleum ether/ether (2:1) gives 3.81 g title compound.

^H-NMR (CDCls): 1.40 - 2.20 (m, ό H); 2.95 (s, 1 H); 3.37 - 4.10 (m, 2 H); 3.87 (s, 3 H); 5.20 - 5.50 (m, 1 H); 6.80 - 7.10 (m, 3 H). d) 1-C5 -Methoxyf 8~ (tet r ahydropy ran-2c,-y loxy )-pheny 13-11-(tetr ahydropyr an2,-yloxy)-undeca-1,9-di ine 1.31 g product from example 5c are dissolved in 9.5 ml absolute tetrahydrofuran, and 3.51 ml n-butyllithium solution are added dropwise at -78°C to -70°C, while stirring and passing over dry nitrogen. The mixture is stirred in a cold bath for a further 60 minutes and a solution of 1.72 g 1-bromo-9-(tetrahydropyran-2-yloxy)~non~7-ine in 5.3 ml absolute hexamethylphosphoric acid triamide is then added dropwise. After about 4 hours, the cold bath is removed. As soon as the reaction mixture has reached 0°C, it is broken down with saturated ammonium chloride solution and extracted three times with ether. The combined ethereal extracts are washed twice with saturated ammonium chloride solution and once with water, dried over sodium sulphate and then evaporated in vacuo. Column chromatography of the residue with petroleum ether/ether (2:1) gives 1.72 g title compound. 1H-NMR (CDCl3): 1,07 - 2.07 (m, 20 H); 2.10 - 2.60 (m, 4 H); 3.27 - 4.07 (m, 4 H); 3.86 (s, 3 H); 4.13 - 4.37 (m, 2 H); 4.67 - 4.91 (m, 1 H); .33 - 5.51 (m, 1 H); 6-67 - 7.07 (m, 3 H). e) The 1-bromo~9~(tetrahydropyran-2B-yloxy)-non-7-ine used in example 5d as one of the starting compounds is obtained as follows: .0 g 3~(tetrahydropyran-2e~y loxy)-prop-1-i ne are dissolved in 70 ml absolute tetrahydrofuran, and 22.31 ml n-butyllithium solution are added dropwise at -78°C to -70°C, while stirring and passing over dry nitrogen. The mixture is stirred in a cold bath for a further 60 minutes and 16.3 ml 1,6-dibromohexane are then added dropwise in the course of 5 minutes, followed by 30 ml absolute hexamethylphosphoric acid triamide in the course of 25 minutes. After 4 hours, the cold bath 2 is removed and the mixture is worked up analogously to example 5d, but the ether extracts are washed with saturated sodium chloride solution. The crude product gives 8.23 g title compound by column chromatography with n-hexane/ether (10:1). 1H-NMR (CDClg): 1.16 - 2.43 (m, 1ό H); 3.20 - 4.05 (m, 4 H); 4.10 - 4.33 (m, 2 H>; 4.61 - 4.90 (m, 1 H). f) 11-Hydroxy-(4!-hydroxy-5t-.methoxyphenyl)-undeca-1,9-diine 1.71 g product obtained in example 5d and 0.08 g pyridinium toluene-4sulphonate are dissolved in 34 ml absolute ethanol and the solution is stirred under dry nitrogen at a bath temperature of 55°C to 60°C for 3 hours and then evaporated in vacuo at a bath temperature of 20° to 25°C. Column chromatography of the residue with petroleum ether/ethyl acetate (3:4) gives 0.720 g title compound, which slowly turns into crystals which melt at 71°C. 1H-NMR (CDClg): 1.16 - 1.83 (m, 8 H); 1.91 - 2.53 (m, 4 H); 3.87 (s, 3 H); 4.20 - 4.37 (m, 2 H); 6.60 - 7.01 (m, 3 H).

Example 6 11-Acetoxy-1-(4,-acetoxy-3,-methoxyphenyl)-undeca-1,9-di ine 0-20 g product from example 5 are reacted in 2 ml absolute tetrahydrofuran with 0.60 ml absolute pyridine and 0.63 ml acetic anhydride analogously to example 4, 0.273 g title compound being obtained. 1H-NMR (CDCl3): 1.20 - 2.53 (m, 12 H); 2.05 (s, 3 H); 2.25 (s, 3 H); 3.70 (s, 3 H); 4.43 - 4.60 (m, 2 H); 6.60 - 7.10 (m, 3 H). 3 Example 7 1-(3 *,4!-Dihydroxypheny()-11-hydroxy-undeca-1,9-diine a) 5,4-Bi s-(tetr ahydr opyran-211-y (oxy)-benzaldehyde A suspension 'of 25 g 3,4-dihydroxybenzaldehyde in 125 ml methylene chloride is reacted with 39.5 ml 3,4-dihydro-2H-pyran under the catalytic action of 0.05 g p-toluenesulphonic acid monohydrate analogously to example 5a and the mixtxure is then worked up. Column chromatography with petroleum ether/ether (3:2) gives 38.42 g title compound, which partly solidifies after some time in a refrigerator. 1H-NMR (CDCl5): 1.33 - 2,.27 (m, 12 H); 3.20 - 4.23 (m, 4 H); 5.23 - 5.63 (m, 2 H); 6.93 - 7.70 (m, 3 H); 9.70 (s, 1 H). b) 1,2-Bis-(tetrahydropyran-2*-yloxy)-4-(2l!lchlorovinyl)-benzene The procedure is analogous to example 5b to give, from 20.0 g chloromethyltriphenylphosphonium chloride, 6.46 g potassium tertbutylate and 11.8 g product from example 7a, after column chromatography with petroleum ether/ether (2:1), 10.56 g title compound. 1H-NMR (CDCl-): 1.40 - 2.40 (m, 12 H); 3.27 - 4.27 (m, 4 H); 5.20 - 5.63 (m, 2 H); .97 - 7.56 (m, 5 H). c) 3,4-Bis-(tetrahydropyran-2-yloxy)-pheny(acety(ene The procedure is analogous to example 5c to give, from 4.0 g chlorovinyl compound prepared in example 7b and 16.24 ml n-butyllithium solution, after column chromatography with petroleum ether/ether (5:1), 2.96 g title compound, which gradually solidifies to a white crystalline mass with a melting range of 58° - 70°C. 4 1H-NMR (CDCl3): 1-37 - 2.33 (m, 12 H): 2.90 (s, 1 H); 3.33 - 4.23 (m, 4 H); .23 - 5.5ό (m, 2 H); 0.83 - 7.33 (m, 3 H). d) 1-C31, 41 - Bi s-(tetrahydropyran"-2-yloxy)~phenyl]-11-(tetrahydropyran-2ayloxy)-undeca-1,9-di ine The procedure is analagous to example 5d to give, from 5.0 g product from example 7c, 10.3 ml n-butyllithium solution, 4.63 g l-iodo-9(tetrahydropyran-2'!~yloxy)-non~7~ine and 15 ml absolute hexamethylphosphoric acid triamide, after column chromatography with petroleum ether/ether (7:2), 5.14 g title compound. 1H-NMR (CDCl3): 1.20 - 2.55 (m, 30 H); 3.27 - 4.25 (m, ό H); 4.10 - 4.53 (m, 2 H); 4.70 - 4-87 (m, 1 H); 5.27 - 5.50 (m, 2 H); 6.83 - 7.27 (m, 3 H). e) The 1-iodo~9~(ietrahydropyran-2'-yLoxy)-non-7-ine used in example 7d is accessible as follows: A solution of 6.23 g sodium iodide in 30 ml absolute acetone is added to 4.20 g 1-bromo~9-(tetrahydropyran-2s-yloxy)-non-7-ine, dissolved in 30 ml absolute acetone, at room temperature, the mixture is left to stand overnight under a nitrogen atmosphere and is evaporated in vacuo, and the residue is taken up in ether/water. The ether phase is separated off, washed with water and saturated sodium chloride solution, dried over sodium sulphate and evaporated in vacuo, 4.66 g title compound being obtained. 1H-NMR (CDCl3): 1.20 - 2.43 (m, 16 H); 3.03 - 3.33 it, 2 H); 3.20 - 4.05 (m, 2 H); 4.13 ~ 4.33 (m, 2 H); 4.67 - 4.87 (m, 1 H). f) 1 - ( 3>J, 41 ~ (i) i h y d r o x y p h e ny I) -11 - hyd r o x y-u n deca-1,9-diine The procedure is analogous to example 5f to give, from 5.10 g product from example 7d, 100 ml absolute ethanol and 0.24 g pyridinium toluene4-sulphonate, after column chromatography with petroleum ether/ether (1:3) and recrystallization from n-hexane/ethyI acetate, 1.91 g title compound in the form of white crystals which melt at 81°C - 83°C. ΊΗ-ΜΜ& (C0Cl3): 1.25 - 2.00 (m, 9 H); 2-03 - 2.60 (m, 4 H); 4.20 - 4.40 (m, 2 H); 6.57 - 7.00 (m, 3 H).

Example 8 11~Acetoxy-1-(51 * *,4^-01acetoxyphenyI)-undeca-1,9-diine The title compound is obtained by acetylation of the product obtained in example 7 using the procedure described in example 4. 1H-NMR (CDClg): 1.20 - 1.83 (m, 8 H); 1.93 - 2.50 (m, 13 H); 4.40 - 4.60 (m, 2 H); 6.73 - 7.20 (m, 3 H). 3 Example 9 1-(3 ,.4S-Dihydroxypheny 1)-11 -hydroxy-undecs-iZ,9Z-di ene 0.545 g product obtained in example 7, dissolved in 20 ml absolute ethanol containing 0.1 ml freshly distilled quinoline, are hydrogenated at room temperature under atmospheric pressure over 0.136 g palladium-on-calcium carbonate (5% Pd; '’Lindlar catalyst" poisoned with lead). After uptake of the theoretical amount of hydrogen, the catalyst is filtered off and the filtrate i s .evaporated in vacuo. The residue is purified by HPLC with methanol/water (60:40), 0.416 g title compound being obtained. 1H-NMR (CDClg): 1.15 - 1-75 (m, 8 H); 1.70 - 2.53 (m, 4 H); 4.07 - 4.33 (m, 2 H); .23 - 6.37 (m, 4 H); 6.47 - 6.90 (m, 3 H). 6 Example 10 The procedure is as in example 9 to give 11-hydroxy-1-(4'~hydroxy-3s methoxyphenyl)-undeca-1Z,9Z-diene from the product of example 5. 1H-NMR 3): 1.10 - 1.70 (m, 8 H); 1.72 - 2.50 (m, 4 H); 3.77 (m, 3 H); 3.80 - 4.13 Cm, 2 H); 5.13 - 0.30 (m, 4 H); 5.53 (s, 1 H); 6.37 6.73 (m, 3 H).

Example 11 - (38,4'-Di methoxypheny1)-11-hydroxy-undeca-1,9-di i ne a) 1-(5*,4-Dimethoxypheny1)-11-(tetrahydropyran-28-yloxy)-undeca~1,9-di i ne The procedure is analogous to example 5d to give, from 0.75 g 3,4di methoxypheny lacety Lene, 2.88 ml n-butyllithium solution, 1.29 g 1iodo-9-(tetrahydropyran"2-yloxy)mnon-7-i ne and 4 ml absolute hexamethylphosphori c acid triamide, after column chromatography with petroleum ether/ether (2:1), 1.17 g title compound 1H-NMR (CDCl3): 1.25 - 1.93 (m, 14 H); 2.03 - 2.53 (m, 4 H); 3.30 - 4.00 (m, 2 H); 3.83 (s, ό H); 4.13 - 4.27 (m, 2 H); 4.07 - 4.87 (m, 1 H); 6.57 - 7.00 (ra, 3 H). b) 1-(5',4°-Pimethoxypheny1)-11-hydroxy-undeca~1,9-di ine The procedure is analogous to example 5f to give, from 1.15 g product from example 11a, 30 ml absolute ethanol and 0.075 g pyridinium toluene4-suIphonate, after column chromatography with n-hexane/ether (1:1), 0.78 g title compound in the form of white crystals which melt at 39° 41 °C.

^H-NMR (CDClg): 1.25 - 1.85 (m, 9 H); 2.05 - 2.55 (m, 4 H); 3.83 (s, ό H); 4.07 - 4.33 (m, 2 H); 6.57 - 7.00 (m, 3 H).

Example 12 11-Hydroxy-1-(3, 4'-methylenedioxyphenyI)-undeca-1,9-di ine a) 1-(54*-Methy Lenedi oxypheny L)-11-(tetrahydropyran-Z'-yloxyj-undeca-l,9diine The procedure is analogous to example 5d to give, from 1.61 g 5,4methylenedioxyphenylacetylene, 6,9 ml n-butyllithium solution, 3.08 g 1iodo-9-(tetrahydropyran-2’-yloxy)-non~7-ine and 10 ml absolute hexamethyIphosphoric acid triamide, after column chromatography with petroleum ether/ether (10:1), 2.60 g title compound. 1H-NMR (CDClg): 1.20 - 1.90 (m, 14 H); 2.03 - 2.53 (m, 4 H); 3.23 - 4.00 (m, 2 H); 4.1^ 4.30 (m, 2 H); 4.65 - < U85 (m, 1 H); 5.85 (s, 2 H); 6.50 - - 6.93 (m, 3 H). b) 11-Hydroxy-1-(38,4s-methylenedi oxyphenyI)-undeca-1,9-dii ne The procedure is analogous to example 5f to give, from 2.51 g product obtained in example 12a, 70 ml absolute ethanol and 0.17 g pyridinium toluene-4-sulphonate, after column chromatography with n-hexane/ether (3:2), 1.41 g title compound in the form of white crystals which melt at 45° - 46°C. 1H-MMR (CDClg): 1.25 - 1.80 (m, 9 H); 2.03 - 2.53 (m, 4 H); 4.07 - 4.33 (m, 2 H); .85 (s, 2 H); 6.50 - 6.93 (m, 3 H). 8 Example 15 1-(5 Β,48-Di hydroxyphenyl )-11-hydroxy-11-rnethyl-dodeca-1,9-di ine a) 1-Bromo-9-methy1-9-(tetrahydropyran-2!-yloxy)-dec-7-ine .05 g 3-methy l~3-(tetrahydropyran-2B-y loxy)-but-1-i ne, 18.8 ml n5 butyllithium solution, 13.9 ml 1,6-dibromohexane and 10 ml absolute hexamethylphosphoric acid triamide are reacted analogously to example 5e. (TLC: petroleum ether/ether - 20:1). After ό hours, the cold bath is removed. As soon as the reaction mixture has reached 0°C, it is worked up analogously to example 5e. Column chromatography with petroleum ether/ether (20:1) gives 6.08 g title compound. 1H-NMR (CDCl3): 1.20 - 2.37 (m, 22 H); 3.23 - 4.13 (m, 4 H); 4.90 - 5.10 (m, 1 H). b) 1~C3a,4"~Bis-(tetrahydropyran-2l,-yloxy)-phenyl3-11-methyl-11-(tetrahydropyran-2Byloxy)-dodeca-1,9-di ine The procedure is analogous to example 5d to give, from 1.51 g 3,4-Bis(tetrahydropy ran~2f-yloxy)-phenylacetylene, 3.13 ml n-butyllithium solution, 1.33 g product obtained in example 13a and 4.5 ml absolute hexamethylphosphoric acid triamide, after column chromatography with petroleum ether/ether (5:1), 1.81 g title compound. 1H~NMR (CDCL3): 1.25 - 2.50 (m, 3ό H); 3.27 - 4.17 (m, ό H); 4.90 - 5.10 (m, 1 H); .23 - 5.43 (m, 2 H); 0.87 - 7.13 (m, 3 H). c) 1-(5l,4*'-Dihydroxyphenyl)-11-hydroxy-11-methyl-dodeca-1,9-di ine The procedure is analogous to example 5f to give, from 1.75 g product from example 13b, 30 ml absolute ethanol and 0.08 g pyridinium toluene4-sulphonate, after column chromatography with petroleum ether/ether (1:3) and recrystallization from n-hexane/ethyI acetate, 0.69 g title compound in the form of white crystals which melt at 71°C to 73°C. 1H-NMR (CDClg): 1.25 - 1.73 (m, 14 H); 1.97 - 2.50 (m, 5 H); 5.40 (s, 1 H); .90 Example 14 1-(31,4'-Di hydroxyphenyl)-11-hydroxy-hexadeca-1,9-diine a) l-CS^A^Bi s-(tetrahydropyrgn-2a8-yloxy)~phenyl38-bromooct-1ine 6.9 ml n-butyllithium solution are added dropwise to a solution of 3.33 g 3,4-Bis"(tetrahydropyran-2,-yloxy)"phenylacetylene in 20 ml absolute tetrahydrofuran at -78° to -70°C in the course of 45 minutes, under dry nitrogen, the mixture is stirred in a cold bath for a further hour and 5.1 ml 1,6-dibromohexane are then added, followed by dropwise addition of 7 ml absolute 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. The mixture is stirred for 20 hours, allowed to warm to 0°C and worked up analogously to example 5e. Column chromatography with toluene/diisopropylether (10:1) gives 3.55 g title compound. 1H-NMR 3): 1.20 - 2.56 (sn, 22 H); 3.23 - 4.23 (m, 6 H); 5.25 - 5.53 (m, 2 H); 6.73 - 7.20 Cm, 3 H). b) 1-^3^,4/-61s-(tetrahydropyran~2~yloxy)-pheny(3-11-(tert-buty(diphenyls iIyIox y)-h e x a de c a-1,9-d1i ne « The procedure followed is according to the process described in example 5d to give, from 1.82 g 3-(tert-buty Idi pheny Isi lyloxy)-oct-1 ~i ne, 3.13 ml n-butyllithium solution, 1.86 g product from example 14a and 4.5 ml absolute hexamethyIphosphoric acid triamide, after column chromatography with petroleum ether/ether (4:1), 2.26 g title compound. 0 1H-NMR (CDCl3): 0.67 - 2.50 (ri, 35 H); 1.07 (s, 9 H); 3.33 - 4.45 (sn, 5 H); .23 - 5.43 (m, 2 H); 6.85 - 7.80 (m, 13 H). c) To prepare the 3-(tert-butyldiphenylsi lyloxy)-oct-1 —ine used in example 14b as one of the starting compounds, 5 mt tert-butyldiphenyIchlorosilane are added dropwise to a solution of 2.03 g oct-1-in~3~ol and 1.32 g imidazole in 20 ml absolute dimethylformamide at 0°C, while stirring and passing over dry nitrogen, and the miture is subsequently stirred at room temperature for 3 hours, diluted with 100 ml methylene chloride and washed in succession in each case once with water, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phase is dried over sodium sulphate and evaporated in vacuo. Column chromatography of the residue with petroleum ether/toluene (8:1) gives 5.34 g title compound. 1H-NMR (CDCl3): 0.63 - 1.87 (m, 11 H); 1.10 (s, 9 H); 2.28 (d, 1 H); 4.13 - 4.43 (m, 1 H); 7.15 - 7.80 (m, 10 H). d) 1-C3^,4-Bis-(tetrahydropyran-2~yloxy)-pheny13-11-hydroxy-hexadeca-i,9diine 9 ml of a solution of tetra-n-butylammonium fluoride in tetrahydrofuran (1 mol/l) are added dropwise to a solution of 2.23 g product obtained in exampLe 14b in 30 ml absolute tetrahydrofuran at 0° - 5°C, while stirring and passing over dry nitrogen, and the mixture is then allowed to warm to room temperature. (TLC: petroleum ether/ether - 3:2). After four hours, the reaction is complete. Saturated ammonium chloride solution is added and the mixture is worked up analogously to example 5e. Column chromatography of the crude product with n-hexane/ether (3:2) gives 1.42 g title compound. 1H-NMR (CDCl3): 0,67 - 2.53 (m, 36 H); 3.33 - 4.43 (m, 5 H); 5.20 - 5.43 (m, 2 H); 6.80 - 7.15 (m, 3 H). ί e) 1- (3/,4"-DihydroxyphenyI)-11-hydroxy-hexadeca-1,9-diine The procedure is analogous to example 5f to give, from 1.40 g product from example 14d, 30 ml absolute ethanol and 0.07 g pyridinium toluene4-sulphonate, after column chromatography with petroleum ether/ether (1:3), 0.73 g title compound in the form of crystals which melt at 46° 48°C. 1H-NMR (CDClg): 0.07 - 1.93 (m, 19 H); 2.00 - 2.50 (m, 4 H); 4.17 ~ 4.57 (m, 3 H); 6.50 - 7.00 (m, 3 H).

Example 15 1-(38,4 -Di hydroxypheny I )-11-hydroxy-n-phenyl-undeca-1,9-di i ne a) 1-13^,4^61 s-(tetrahydropyran-2-yloxy)-phenyl3-deca-1,9-diine 2.1 ml absolute dimethylsulphoxide are poured over 0-237 g lithium acetylide-ethylenediamine complex (95%) and the mixture is stirred at room temperature for 30 minutes under dry nitrogen. A solution of 1.0 g 1-C3!,4!-bis-(tetrahydropyran"2'’-yloxy)-phenyl3"8-bromo-oct-1-i ne in 1.5 ml absolute dimethylsulphoxide is carefully added dropwise to the mixture, cooled to +8°C, at a temperature of 8° - 9°C. The cooling bath is removed and the mixture is subsequently stirred at room temperature for 3 hours. It is then broken down with saturated ammonium chloride solution and worked up analogously to example 5e. Column chromatography of the crude product with petroleum ether/ether (4:1) gives 0.689 g title compound. 1H-NMR (CDClg): 1.30 - 2.55 (m, 25 H); 3.33 - 4.20 (m, 4 H); 5.23 - 5.47 (m, 2 H); 6.83 - 7.15 (m, 3 H). b) 1-E3',4*-Bis-(tetrahydropyran-2-yloxy)-pheny13-11-oxo-11-phenyl-undeca1,9-diine 0-ό4 g product from example 15a is dissolved in 10 ml absolute triethylamine, and first 0-18 ml benzoyl chloride and then 0.032 g bis(triphenylphosphine)-palladium(II) chloride and 0.015 g copper(I) iodide are added, while stirring and passing over dry nitrogen. (TLC: petroleum ether/ether - 2:1). When the reaction has ended, the mixture is diluted with 50 ml ether and filtered and the filtrate is evaporated in vacuo. Column chromatography of the oily residue with petroleum ether/ether (3:1) gives 0.66 g title compound. 1H-NMR (CDClj): 1.25 - 2.10 (m, 20 H); 2.15 - 2.67 (m, 4 H); 3.30 - 4.20 (m, 4 H); .23 - 5.47 (m, 2 H); 6.80 - 8.17 (ra, 8 H). c) 1-C3',4*-Bis-(tetrahydropyran-2,8-yloxy)-pheny13-11-hydroxy-11-phenylundeca-1,9-di ine 0.64 g compound obtained in example 15b is dissolved in 3 m I of a solution of cerium(Iil) chloride in methanol (0.4 mol/l), and a total of 0.047 g sodium borohydride is added in three portions at room temperature, while stirring and passing over dry nitrogen. After 30 minutes, the mixture is broken down by dropwise addition of 1.2 ml buffer solution pH 7- 10 ml methylene chloride and 1 ml saturated potassium sodium tartrate soLution are added, the organic phase is separatead off and the aqueous layer is extracted twice with 10 ml methylene chloride each time. The combined organic phases are washed in each case once with saturated sodium bicarbonate solution and saturated sodium chloride solution and dried over sodium sulphate. Column chromatography, with petroleum ether/ether (1:1), of the crude product obtained by evaporation in vacuo gives 0.60 g title compound. 1H-NMR (CDClj): 1.25 - 2.53 (m, 25 H); 3.33 - 4.20 (m, 4 H); 5.23 ~ 5.50 (m, 3 H); 6.83 - 7.57 (m, 8 H). 3 d) 1 - (3a,4-pihydroxyphenyI)-11-hydroxy-11-phenyl-undeca-1,9-diine By the process described in example 5f, 0.58 g product from example 15c, 12.5 ml absolute ethanol and 0.03 g pyridinium toluene-4-sulphonate give, after column chromatography with n-hexane/ether (1:2), 0.283 g title compound in the form of crystals which melt at 93° - 95°C. 1H-NMR (CDClg): 1.23 - 1.83 (m, 9 H); 2.07 - 2.53 (m, 4 H); 5.20 - 5.70 (m, 3 H); 0.50 - 7.57 (m, 8 H).

Example 16 0 11-Cyclohexy1-1-(3/,41-dihydroxypheny1)-11-hydroxy-undeca-1,9-di ine a) 1-C5i,4t~Bis-(tetrahydropyran-2ia-yloxy)-phenyl3-11-cyclohexyl-11hydroxy-undeca-1,9-di ine 1.66 ml n-butyllithium solution are added dropwise to a solution of 1.09 g product obtained in example 15a in 10 ml absolute tetrahydrofuran at 15 70°C, while stirring and passing over dry nitrogen. The mixture is subsequently stirred for 30 minutes, during which the temperature is allowed to rise to -10°C, and 0.48 ml cyclohexanealdehyde is then added dropwise. The mixture is kept for in each case a further hour at -10°C and then at room temperature. It is then broken down with 5 ml saturated ammonium chloride solution and worked up analogously to example 5e. Column chromatography of the erude product with petroleum ether/ether (2:1) gives 0.94 g title compound. 1H-NMR (CDClg): 0.70 - 2.50 Cm, 36 H); 3.26 - 4.20 Cm, 5 H); 5.23 - 5.43 (m, 2 H); 6.83 - 7.15 (m, 3 H). b) 11-Cyclohexyl-1-(5a,4-dihydroxyphenyI)-11-hydroxy-undeca-1,9-di ine By the procedure described in example 5f, 0.91 g product obtained in 4 example 16a, 18 ml absolute ethanol and 0.04 g pyridinium toluene-4sulphonate give, after column chromatography with n-hexane/ether (2:5), 0.44 g title compound. 1H-NMR (CDCl3): 0.70 - 2.50 (rn, 24 H); 3.93 - 4.20 (m, 1 H); 5.43 (s, 1 H); .87 (s, 1 H); 6.50 - 6.90 (m, 3 H).

Example 17 11-Hydroxy-1(3°,4,,5t'-trimethoxyphenyl)-undeca-1,9-di ine a) 5-(2* 1-Chlorovinyl)-1,2,3-trimethoxy-benzene 21.5 ml n-butyllithium solution are added dropwise to a suspension of 11.94 g chloromethyl-tri pheny Iphosphonium chloride in 85 ml absolute dimethylsulphoxide and 170 ml absolute tetrahydrofuran at 0°C, while stirring and passing over dry nitrogen, the mixture is subsequently stirred for 30 minutes, 5.48 g 3,4,5-trimethoxybenzaldehyde, dissolved in 20 ml absolute tetrahydrofuran, are added dropwise to the resulting solution and the mixture is stirred at 0°C for a further 30 minutes and then allowed to warm to room temperature. After about 4 hours, it is worked up analogously to example 5e. Column chromatography of the crude product with petroleum ether/ether (2:1) gives 4.64 g title compound. 1H-NMR (CDCl3): 3.83 (s, 9H); 6.05 - 6.93 (rn, 4 H). b) 3,4,5-Trimethoxyphenylacetylene Using the procedure described in example 5c, 4.60 g product from example 17a and 28.2 ml n-butyl li thiurn solution give 3.47 g crude product. Recrystallization from n-hexane gives 3.09 g title compound in the form of white crystals which melt at 68° - 70°C. nH-mR (CDCl3): 2.97 (s, 1 H); 3.77 (s, 9 H); 0.60 (s, 2 H). c) 11-(Tetrahydropyran-2!l-yloxy)~1(5,,4!',5l,-trimethoxyphenyl)~undec5~1,9diine The procedure is analogous to example 5d to give, from '1.73 g product from example 17b, 5.65 ml n-butyI lithium solution, 2.10 g l-iodo-9(tetrahydropyran-2'’-yloxy)-non-7-ine and 7.5 ml absolute hexamethylphosphoric acid triamide, after column chromatography with petroleum ether/ether (2:1), 1.94 g title compound. 1H-NMR (CPCl3): 1.30 " 1.93 (m, 14 H); 2.05 - 2.53 (m, 4 H); 3.27 - 4.03 Cm, 2 H); 3.80 (s, 9 H); 4,,13 - 4.27 (m, 2 H); 4.67 - 4.83 (m, 1 H); 6.53 (s, 2 H). d) 11—Hydroxy—1 —(3,J, 48,5 ;-tr imethoxypheny D—undeca—1,9—di i ne The procedure is analogous to example 5f to give, from 1.91 g product obtained in example 17c, 40 ml absolute ethanol and 0.09 g pyridinium toluene-4-sulphonate, after column chromatography with n-hexane/ether (1:1), 1.38 g title compound. 1H-NMR (CDCl3): 1.33 - 1.83 (m, 9 H); 2.05 - 2.57 (m, 4 H); 3.80 (s, 9 H); 4.10 - 4.30 (m, 2 H); 6.53 Cs, 2 H).

Example 18 1-(5',5!-Di methoxy-4*-hydroxypheny1)-11-hydroxy-undec a-1,9-di i ne a) 4-(tert-ButyIdi methyI silyloxy)-3,5-dimethoxy-benzaldehyde 2.05 g 3,5-dimethoxy-4-hydroxybenzaldehyde and 0.91 g imidazole in 15 ml absolute dimethylformamide are reacted with 2.05 g tert-butyldimethylchlorosilane under the conditions described in example 14c. The crude product is purified by chromatography on silica gel 60 (0.063 - 0.200 mm) with petroleum ether/ether (1:1), 2.91 g title compound being obtained in the form of crystals which melt at 68°C. 1H-NMR (CDClg): 0.20 (s, 6 H); 1.03 (s, 9 H); 3.83 (s, 6 H). 7.00 (s, 2 H); 9.67 (s, 1 H). b) 2-(tert-ButyldimethylsilyLoxy)-5-(2‘-chloroviny1)-1,3-dimethoxy-benzene The procedure is analogous to example 17a to give, from 2.90 g product 10 obtained in example 18a, 4.08 g chloromethyltriphenylphosphonium chloride and 7.4 ml n-butyllithium solution, after column chromatography with petroleum ether/ether (3:1), 2.74 g title compound. 1H-NMR (CDClg)s 0.13 (s, 6 H); 1.03 (s, 9 H); 3.75 (s„ 6 H); 5.97 - 6.83 (m, 4 H). c) 4-(tert-Butyldimethylsilyloxy)-5,5-dimethoxy-phenylacetyLene The procedure is analogous to example 5c to give, from 2.72 g product from example 18b and 11.65 ml n-butyllithium solution, after purification by chromatography on silica gel 60 (0.063 - 0.200 mm) with petroleum ether/ether (4:1), 1.89 g title compound in the form of crystals which melt at 35° - 38°C. 1H-M (CDClg): 0.15 (s, 6 H); 1.03 (s, 9 H); 2.95 (s, 1 H); 3.75 (s, 6 H); 6.63 (s, 2 H). d) 1-041-(tert-butyIdimethyIsilyΙοχν)-5,58-dimethoxyphenyl]-11-(tetra™ hydropyran-2-yloxy)-undeca-1,9-diine The procedure is analogous to example 5d to give, from 1.85 g product obtained in example 18c, 3.95 ml n-butyllithium solution, 1.48 g 1-iodo~ 7 9-(tetrahydropyran-2E-yloxy)"non-7-i ne and 5.3 ml absolute hexamethylphosphoric acid triamide, after column chromatography with petroleum ether/ether (3:1), 1..22 g title compound. '’h-NMR (CDC I-): 0.13 (s, ό H); 1.03 (s, 9 H); 1.23 - 1.97 (m, 14 H); 2.00 ~ 2.50 (m, 4 H); 3.25 - 3.95 (m, 2 H); 3.75 (s, ό H); 4.13 - 4.30 (m, 2 H); 4.07 - 4.87 (m, 1 H); 6.53 (s, 2 H). e) 1-(5l!,5,-Pimethoxy-4,-hydroxyphenyl)-11~hydroxy-undeca-1,9-diine ml of a methanolic solution of hydrogen chloride (3%) are poured, under dry nitrogen, over 1.19 g product obtained in example 18d and the mixture is stirred at room temperature, the compound employed gradually dissolving. (TLC: n~hexane/acetone - 3:2). When the reaction has ended, the reaction mixture is poured carefully into 50 ml saturated sodium bicarbonate solution. It is extracted several times with 30 ml ether each time and the extracts are washed in each case once with saturated sodium bicarbonate solution and sodium chloride solution and dried over sodium sulphate. The crude product obtained by evaporation in vacuo is first pre-purified by column chromatography with nhexane/acetone (3:2). HPLC with methanol/water (70:30) then gives 0.428 g title compound. 1H-NMR (CDCl3): 1.23 - 1.83 (m, 9 H); 2.00 - 2.53 (m, 4 H); 3.80 (s, 6 H); 4.05 - 4.30 (m, 2 H); 5.45 (s, 1 H); 6.53 (s, 2 H).

Example 19 11-Hydroxy-1-(38-hydroxy-4!!-methoxyphenyl)-undeca-1,9-di ine a) 4-Methoxy-3-(tetrahydropyran-28-yIoxy)-benzaldehyde .0 g isovanillin, suspended in 320 ml methylene chloride, are reacted with 14.28 ml 3,4-dihydro-2H-pyran in the presence of 0.20 g p-toluenesulphonic acid monohydrate analogously to example 5a and the mixture is then worked up. Column chromatography of the crude product with petroleum ether/ether (1:1) gives 24.85 g title compound. 1H-NMR (CDCl3): 1.40 - 2.27 (m, ό H); 3-26 - 4.10 (m, 2 H); 3.87 (s, 3 H); .20 - 5-47 (m, 1 H); 6.60 - 7-56 (m, 3 H); 9.54 (s, 1 H). b) 4-(2t-Chloroviny()-2-(tetrahydropyran-2l-yloxy)-anisole The procedure is analogous to example 5b to give, from 20.0 g chloromethy Itriphenylphosphonium chloride, 6.46 g potassium tert-butylate and 9.0 g product obtained in example 19a, after column chromatography with petroleum ether/ether (1:1), 8-43 g title compound. 1H-NMR (CDCL3): 1.37 - 2-10 (m, 6 H); 3.30 - 4.13 (tn, 2 H); 3.82 - 3-83 (s,s 3 H); .11 - 5-37 (m, 1 H); 5-80 - 7.43 (m, 5 H). c) 4-Methoxy-3-(tetrahydropyran-2l!-yloxy)-phenylacetylene The procedure is analogous to example 5c to give, from 2.92 g chlorovinyl compound prepared in example 19b and 14.73 ml n-butyllithium solution, after column chromatography with petroleum ether/ethyl acetate (2:1), 2.02 g title compound. 1H-NMR (CPC 1-): 1.37 - 2.05 (m, 6 H); 2.87 (s, 1 H); 3.25 - 4.05 (m, 2 H); 3.80 (s, 3 H); 5.07 - 5.33 (m, 1 H); 6-40 - 7.20 Cm, 3 H). d) 1-C4l-Methoxy-3,-(tetrahydropyran-2-yloxy)-phenyl]-11-(tetrahydropyran2Eyloxy)-undeca-1,9-diine By the process described in example 5d, 1.90 g product from example 19c, .11 ml n-butyllithium solution, 2.47 g 1-bromo~9-(tetrahydropyran-2"y loxy)-non-7-i ne and 5.70 ml 1,3-di methyl-3,4,5,6-tetrahydro-2-(1H)4 9 py ri mi di none give, after column chromatography with petroleum ether/ ether (2:1), 3.14 g title compound. 1H-NMR (CDClg): 1.20 - - 2.53 (m, 24 H); 3.16 - 4-10 (m, 4 H); 3.83 (s, 3 H); 4.13 - - 4.27 (m, 2 H); 4-56 - 4.80 (ra, 1 H); 5.16 - 5.37 (m, 1 H); 6.43 - 7.07 (m, 3 H). e) 11-Hydroxy-1-(58-hydroxy-4t-methoxyphenyI)-undeca-1,9-di ine The procedure is analogous to example 5f to give, from 3.0 g product from example 19d, 60 ml absolute ethanol and 0.150 g pyridinium toluene4-sulphonate, after column chromatography with ethyl acetate/petroleum ether (4:3), 1.61 g title compound in the form of colourless crystals which melt at 77°C to 78°C. 1H-NMR (CDClg): 1.20 - 1.87 (m, 8 H); 1.98 - 2.53 Cm, 4 H); 3.80 (s, 3 H); 3,93 - 4.23 (m, 2 H); 6.50 - 7.02 (m, 3 H).

Example 20 The procedure is analogous to example 1, but instead of the methyl 5iodosalicylate a) n-propyl 5-iodosalicylate or b) 5-iodosalicylic acid piperidide are used, to give in this way a) 1-(4'-hydroxy-3’~n~propoxycarbonyl"phenyl)-11-hydroxy-undeca-1,9-diine 1H-NMR (CDClg): 0.77 - 2.53 (m, 17 H); 3-77 - 4.37 (m, 4 H); 6.40 - 7.53 (m, 3 H); .47 (s, 1 H). and Ο b) 1-C4’-hydroxy-3‘-(Ν,Ν-pentamethy lenecarbamoyI)-pheny13-11-hydroxyundeca-1,9-di ine. 1H-NMR (CDCl3): 1.25 - 1.95 (m, 15 H); 1.95 - 2.50 (m, 4 H); 3.35 - 3.70 (m, 4 H); 4.05 - 4.23 (m, 2 H); 6.57 - 7.23 (m, 3 H).

Example 21 The procedure is as in example 3, but instead of the ammonia, 2-aminoethanol is used to give, from the ester shown in example 1, 1~C3-(2’'~ hydroxyethyl-carbamoyI)-4*-hydroxypheny13-11-hydroxy-undeca-1,9-diine. 1H-NMR (C0Cl3): 1.16 - 2.53 (m, 12 H); 3.27 - 4.23 (m, 6 H); 6.52 - 6.83 (m, 1 H); 6.84 - 7.33 Cm, 3 H); 10.77 (s, 1 H).

Example 22 Using the corresponding starting materials, the procedures described, in particular those explained in more detail in examples 1 - 21, give: a) 11-eye lohexy I—1-(4’-hydroxy-3’-methoxyphenyl)-11-hydroxy-undeca-1,9diine; 1H-NMR (CDCl3): 0.71 - 2.73 (m, 23 H); 3.90 - 4.27 (tn, 1 H); 3.91 (s, 3 H); .63 (s, 1 H); 6.60 - 7.07 (m, 3 H). b) 11 -eyelohexy1-1-(3’,5'-dimethoxy-4*-hydroxyphenyI)-11-hydroxy-undeca1,9-diine; 1H-NMR (CDCl3): 0.90 - 1.97 (m, 20 H); 1.95 - 2.47 (m, 4 H); 3.80 (s, 6 H); 3.80 - 4.17 (sn, 1 H); 5.43 (s, 1 H); 6.47 (s, 2 H). 1 c) 11-cy clohexy1-1-(34’-dihydroxyphenyI)-11-hydroxy-undec-9E-en~1~ine 1H-NMR (CDClj): 0.85 - 2.53 (m, 24 H); 3-57 - 3..93 (m, 1 H); 5.10 - 5.80 (η, 3 H); 6.13 (s, 1 H); 6.47 - 6.83 (ra, 3 H). and from these, by hydrogenation analogously to example 9, d) 11-cyc lohexy 1-1-(3',4l-di hydroxypheny I )-11-hydroxy-undeca-12,9E-di ene; 1H-NMR (CDClj): 0.85 - 2.45 (m, 23 H); 3.50 - 3.83 (tn, 1 H); 5.05 - 6.80 (ra, 7 H). e) 1-(4-hydroxy-5-methoxy-58 -methoxycarbonyl-phenyU-H-hydroxy-undeca1,9-diine; 1H-NRR (CDClj): 1.23 - 2.53 (m, 12 H); 3.30 Cs, 3 H); 3.87 (s, 3 H); 3,93 - 4.23 (m, 2 H); 6.60 - 6.83 (d, 1 H); 7.10 - 7.33 (d, 1 H); .60 Cs, 1 H).

Example 23 1-(3, 48 -Di hydroxypheny 1)-11 -hydroxy-undec-1 Z-en-9-i ne a) 1-(tert-Butyldiphenylsilyloxy)-prop-2-ine 2.9 ml 2-propi n-1-ol, 15.6 ml tert-butyldiphenylchlorosilane and 4.1 g imidazole are reacted analogously to example 14c. Chromatography of the crude product over siliga gel 60 (0.063 - 0.200 mm) with petroleum ether/diisopropyl ether (20:1) gives 13.3 g title compound in the form of crystals which melt at 55 - 58°C. 1H-MMR (CDClj): 1.07 (s, 9 H); 2.30 - 2.43 (t, 1 H); 4.20 - 4.37 (d, 2 H); 7.15 7-75 (m, 10 H). ΕΓ O' b) 1-Bromo-IQ-(tert-butyIdiphenyLsiLyloxy)-dgc~8-ine The procedure is analogous to example 5e to give, using 7.36 g product from example 23a, 15.63 ml n-butyllithium solution, 12.8 ml 1,7-dibromoheptane and 22 ml absolute hexamethyIphosphoric acid triamide, afer column chromatography with n-hexane/toluene (3:1), 6.96 g title compound.

(CDClg): 1.07 (s, 9 H); 1.10 - 2.27 (m, 12 H); 3.20 ~ 3.50 (t, 2 H); 4-17 - 4.35 (m, 2 H); 7.17 - 7.75 (m, 10 H). c) ClQ-(tert~ButyIdiphenylsilyLoxy)-dec-8-in-1-yL3-triphenyIphosphoniurn bromide A solution of 5.66 g product from example 23b and 3.45 g triphenylphosphine in 36 ml absolute acetonitrile is heated under reflux for 6 days. It is then evaporated in vacuo and the residue is extracted by shaking five times with diethyl ether and dried over phosphorus pentoxide. 7.44 g title compound are obtained in the form of a hygroscopic solid. 1H-NMR (CDClg): 1.07 (s, 9 H); 1.05 - 1.83 (m, 10 H); 1.85 - 2.15 (ra, 2 H); 3.40 - 3.95 (m, 2 H); 4.10 - 4.30 (m, 2 H); 7.00 - 7.87 (m, 25 H). d) 1-C3,4-Bis-(tert-butyIdimethyIsilyloxy)-pheny13-11-(tert-butyIdipheny I si lyloxy)-undeclZ~en~9ine 4.7 ml n-butyllithium solution are added dropwise to a solution of 5.50 g product from example 23c in 40 ml absolute dimethylsulphoxide and 80 ml absolute tetrahydrofuran at -10°C, while stirring and passing over dry nitrogen. The mixture is subsequently stirred for 15 minutes and a solution of 1.84 g 3,4-bi s-(tert-buty Idi methy lsi ly loxy)-benzaldehyde in 5 ml absolute tetrahydrofuran is then added dropwise. After stirring at ~10°C for 1 hour, the mixture is allowed to warm to room temperature and is broken down after a further 4 hours with 20 tai saturated ammonium chloride solution. The crude product obtained during working up (analogously to example 5e) is purified by column chromatography with petroleum ether/toluene (8:1), 1.94 g title compound being obtained. 1H-NMR (CDClg): 0.20 (s, 12 H); 0.70 - 1.55 (m, 35 H); 1.90 - 2.45 (m, 4 H); 4.13 - 4.30 (m, 2 H); 4.90 - 6.25 (m, 2 H); 6.50 - 6.80 (m, 3 H); 7.05 - 7.65 (m, 10 H). e) To prepare the 3,4-bis-(tert-butyldimethylsilyloxy)-benzaldehyde used in example 23d, 2.14 g 3,4-dihydroxybenzaldehyde, 5.83 g tert-butyldimethyIchlorosilane and 2.58 g imidazole are reacted analogously to example 14c to give, after chromatography with petroleum ether/ether (6:1), 3.57 g title compound in the form of crystals which melt at 44° 46°C. 1H-NMR (CDClg): 0.20 (s, 12 H); 0.90 9.47 Cs, 1 H). f) 1-(5/,4^-01hydroxypheny1)-11-hydroxy-undec-1Z-en-9-ine The procedure is analogous to example 14d to give, from 3.52 g product 20 from example 23d and 42.8 ml of a solution of tetra-n-butyl-ammonium fluoride in tetrahydrofuran (1 mol/l), after column chromatography with petroleum ether/ethyl acetate (1:1) and HPLC purification with methanol/water (6:4), 1.29 g title compound. 1H-NMR (CDClg): 1.10 - 1.67 (m, 8 H); 1.90 - 2.45 Cm, 5 H): 4.0? - 4.30 Cm, 2 H); .15 - 6.83 (m, 7 H).

Example 24 I- (4°-Hydroxy-311-methoxyphenyl )-11-hydroxy-hexadeca-1,9-di ine 2.70 g product from example 5c are reacted with Ι,ό-dibromohexane analogously to example 13a, the resulting 8-bromo-1-[3s-methoxy-4'-(tetra5 hydropyran-2,e-yloxy)-phenyl3~oct1-ine is reacted with lithium acetylideethylenediamine complex analogously to example 15a, the product is then reacted with n-hexanal analogously to example 16a and finally the protective group is split off, analogously to example 5f, from the 11hydroxy-1-C3-methoxy~4’~(tetrahydropyran-2’~yloxy)-phenyU~hexadeca-1,910 diine thus obtained. Column chromatography of the crude product with ether/petroleum ether (1:1) gives the pure title compound. 1H-NHR (C0Cl3)x 0.56 - 2.55 (m, 23 H); 3.77 (s, 3 H); 3.97 - 4.40 (m, 1 H); .43 (s, 1 H); 6.51 - 6.77 (m, 3 H).

Example 25 II- Cyclohexyl-1-(3',5°dimethoxy43-hydroxyphenyl)-11-hydroxy-undec9E-en1-i ne a) 4-(tert-butyldiphenyIsilyloxy)-5,5dimethoxy-phenylacetylene Using 3,5-dimethoxy-4-hydroxybenzaldehyde and tert-butyldipheny Ich loro20 silane and the other starting materials mentioned in examples 18a - c and the procedures described therein, the title compound is obtained in the form of crystals which melt at 83° - 85°C.

(C0Cl3): 1.07 (s, 9 H); 2.83 (s, 1 H); 3.33 (s, ό H); 6.40 (s, 2 H); 6.97 - 7.60 (m, 10 H). b) 1-(141-(tert-Butyldiphenylsi lyloxy)-3ll,5!'-dimethoxyphenyl3-9-(tetrahydropyran-2lt-yloxy)-non-1-ine The procedure is analogous to example 5d to give, from 14.58 g product from example 25a, 21.9 ml n-butyllithium solution, 6.98 g 1-bromo~7(tetrahydropyran-2'-y loxy)-heptane and 55 ml absolute hexamethylphosphoric acid triamide, after column chromatography with petroleum ether/ ether (5:1), 10.27 g title compound. 1H-NMR (CDCI-): 0.75 - 1.90 (m, 16 H); 1.07 (s, 9 H); 2.10 - 2.47 (m, 2 H); 3.07 - 3.97 (m, 4 H); 3.35 (s, ό H); 4.37 ~ 4.57 (m, 1 H); 6.30 (s, 2 H); 6.97 - 7.65 (m, 10 H). c) 1E48-(tert~Butyldiphenylsi lyloxy)-3,5*-dimethoxypheny(3-9-hydroxy-non1-ine From 10.22 g product obtained in example 25b, 130 ml absolute ethanol and 0.38 g pyridinium toluene-4-suIphonate, analogously to example 5 f and after column chromatography with petroleum ether/ethyl acetate (1:1), 70.98 g title compound are obtained. 1H-NMR (CDCl3): 1.07 (s, 9 H); 1.15 - 1.80 (m, 11 H); 2.10 - 2.50 Cm, 2 H); 3.33 (s, 6 H); 3.35 - 3.70 (m, 2 H); 6.30 (s, 2 H); 6.97 - 7.65 (m, 10 H). d) 1-C4'-(tert-Butyldiphenylsilyloxy)-5 ^,51-dimethoxyphenyl3-non~1~in-9-aI in 0.37 g anhydrous sodium acetate and then, in portions, 0.75 g pyridinium chlorochromate are added to a solution of 1.20 g product obtained in example 25c in 22.5 ml absolute methylene chloride at room temperature, while stirring and passing over dry nitrogen. The reaction has ended after about 2 hours. (TLC: petroleum ether/ether - 1:1). The mixture is filtered, the filtrate is concentrated to a volume of about 2 ml and the concentrate is chromatographed with petroleum ether/ether (3:2), 0.87 g title compound being obtained. 1H-NMR (CDCl3): 1.07 (s, 9 H); 1.15 - 1.83 (m, 8 H); 2.10 - 2.57 (m, 4 H); 3.33 (s, ό H); 6.50 (s, 2 H); 6,97 - 7-67 (m, 10 H); 9.57 - 9-70 (t, 1 H). e) 1-C4!l-(tert-Buty Idi pheny Isi lyloxy)-3* l *,5>'-dimethoxyphenyl3-11-cyclohexyl-Π-oxo-undec~9E-en~1-ine 1.15 ml n-butyllithium solution are added dropwise to a solution of 0.45 g dimethyl (2-cycLohexyl-2-oxoethyl)-phosphonate in 15 ml absolute tetrahydrofuran, while stirring and passing over dry nitrogen, such that the internal temperature remains below 5°C. The mixture is subsequently stirred for 15 minutes and a solution of 0.85 g product from example 25d in 7.5 ml absolute 1,2-dimethoxyethane is then added dropwise at the same temperature. The reaction mixture is stirred for a further 2 hours, during which it is allowed to warm to room temperature, and is then broken down with saturated ammonium chloride solution and worked up analogously to example 5e. Column chromatography of the crude product with petroleum ether/ether (5:1) gives 0.78 g title compound. 1H-NMR (CPCl3): o„9O - 2-50 (m, 23 K); 1-07 (s, 9 H); 3.33 (s, 6 H); .83 - 6-95 (m, 2 H); 6-30 (s, 2 H); 7.00 - 7-67 (m, 10 H). f) 1-C48-(tert-Butyldiphenylsi lyloxyl-o^S^-dimethoxyphenyU-ll-cyclohexy1-11-hydroxy-undec-9E-en-1-ine The procedure is analogous to example 15c to give, from 0.74 g product from example 25e in 3 ml of a solution of cerium(IXI) chloride in methanol (0.4 mol/l) with 0.049 g sodium borohydride, after column chromatography with petroleum ether/ether (2:1), 0.70 g title compound. 1H-NMR (CPCl3): 0.80 ~ 2.45 (m, 24 H); 1-07 Cs, 9 H); 3.33 (s, ό H); .7 3-50 - 3-83 (in, 1 H); 5-05 - 5.60 (m, 2 H); 6.30 Cs, 2 H): 6.97 - 7-67 (m, 10 H). g) Π-Cyclohexy1-1-(5^,58-dimethoxy-A-hydroxyphenyI)-11-hydroxy-undec-9E~ en-1-ine The procedure is analogous to example 14d but is carried out at room temperature to give, from 0.64 g product from example 25f with 3 ml of a solution of tetra-n-butylammonium fluoride in tetrahydrofuran, after column chromatography with petroleum ether/ethyl acetate (3:2), 0-36 g title compound. 1H-NMR (CDClg): 0.75 - 2.53 (m, 24 H); 3-55 - 3-90 Cm, 1 H); 3-80 (s, 6 H); .07 - 5.70 (m, 3 H); 6.47 (s, 2 H).

Example 26 1-(3,,4’-Dimethoxyphenyl)-11-hydroxy-undec-lE-en-9ine and the corresponding IZ-Isomer a) 10-(tert-ButyLdiphenylsilyloxy)-dec-8-in~1-al Using 8-87 g product from example 23a, 118.8 ml n-butyllithium solution, 6.73 g 1"bromo-7-(tetrahydropyran-2s~yloxy)-heptane and 28-5 ml absolute hexamethylphosphoric acid triamide, 8-92 g 1-(tert-butyldiphenylsi lyloxy)"10-(tetrahydropyran-28~yloxy)-dec"2-ine are obtained analogously to example 5d, from which the protective group is split off analogously to example 5f. The 1-(tert-butyldiphenyl-silyloxy)l0-hydroxy-dec-2"ine thus obtained is then oxidised analogously to example 25d to give the title compound, which is purified by chromatography with petroleum ether/ether (2:1). 1H-NMR (CDClg): 1.07 (s, 9 H); 1.10 - 1.77 (ra, 8 H); 1.93 - 2.53 (m, 4 H); 4.10 ~ 4.27 (t, 2 H); 7.05 - 7.63 (m, 10 H); 9.40 - 9.55 (t, 1 H). b) 11-(tert-ButyIdiphenyIsilyloxy)-1-(3,,4,-dimethoxyphenyl)-undec-1E,Z-en9-i ne 0.392 g potassium tert-butylate is added in portions to a suspension of 1.571 g 3,4-dimethoxybenzy Itriphenylphosphonium chloride in 8 ml absolute tetrahydrofuran at 2 to 5°C, while stirring and passing over dry nitrogen. The mixture is stirred for 30 minutes, a solution of 0.841 g product from example 26a in 3 ml absolute tetrahydrofuran is added dropwise in the course of 5 minutes and after a further 60 minutes the mixture is diluted with about 15 ml ethyl acetate. The mixture is washed in each case once with saturated solutions of ammonium chloride or sodium chloride and then dried over sodium sulphate and evaporated. Column chromatography with ether/petroleum ether (1:10) gives 0.698 g title compound. 1H-NMR (CDC3); 0.12 - 2.43 (m, 21 H); 3.77 (s, ό H); 4.03 - 4.23 (tn, 2 H); .11 - 6.73 (m, 5 H); 6.91 - 7.67 (m, 10 H). c) 1-(3B,48-Di methoxyphenyU-H-hydroxy-undec-IE^Z-en^-ine and the corresponding 1E- and 12-isomer The procedure is analogous to example 14d to give, from 0.452 g product from example 26b with 1.26 ml of a solution of tetra-n-butylammonium fluoride in tetrahydrofuran, after column chromatography with ether/ petroleum ether (2:1), 0.223 g title compound. 1H-NMR (CDCl3): 1.13 - 2.51 (m, 12 H); 3.80 (s, 6 H); 3.94 - 4.23 (m, 2 H); .10 - 6.37 (m, 2 H); 6.43 - 6.73 (m, 3 H).

The isomer mixture obtained in the synthesis of the title compound can be resolved by HPLC with methanol/water (7:3) to isolate the IE- and the 1Z-isomers 1E-isomer: 1H~MMR (CDClg): 1.10 - 2.50 (m, 12 H); 3.73 (s, 3 H); 3.77 (s, 3 H); 3.87 - 4.27 (ra, 2 H); 5.53 - 0.33 (m, 2 H, 3J : 15 Hz); 6.40 - 6.75 (rn, 3 H). 1Z-Zsomer: 1H-NMR (CDCl): 1.10 - 2.50 (m, 12 H); 3.73 (s, 6 H); 3.90 - 4.20 (m, 2 H); .10 - 6.30 (m, 2 H; 3J : 11 Hz); 6.57 - 6.70 (m, 3 H).

Example 27 1-(3,,5-Dimethoxy-4l!-hydroxyphenyl)-11-hydroxy-undec"9Z-en-1-ine a) 9-Bromo-1-C4!l-(tert-buty Idipheny LsilyLoxy)-3,5'-dimethoxyphenyL]™non-1ine 6.74 g carbon tetrabromide are added in portions to a solution of 6.11 g 15 product from example 25c and 5.33 g triphenylphosphine in 230 ml absolute methylene chloride at 0°C, while stirring and passing over dry nitrogen. After the mixture has been stirred for two hours, it is evaporated in vacuo and 240 ml petroleum ether and 12 ml ether are added to the residue. The mixture is filtered, the filtrate is evaporated and the residue is purified by column chromatography with petroleum ether/ ether (20:1), 6.47 g title compound being obtained. 1H-NMR (CDClg): 1.07 (s, 9 H); 1.20 - 2.03 Cm, 10 H); 2.15 - 2.50 (m, 2 H); 3.17 - 3.47 (m, 2 H); 3.33 (s, 6 H); 6.30 (s, 2 H); 7.00 - 7.65 (m, 10 H). 0 b) 2~(tertButyIdiphenyLsilyloxy)-acetaldehyde .15 g glyclolaldehyde and 26.78 ml tert-butyIdiphenyIchlorosiLane are reacted in the presence of 7.61 g imidazole and 26 ml absolute dimethylformamide under the conditions described in example 14c to give, after column chromatography with ether/petroleum ether (1:2), 21.26 g title compound.

^H-NMR (CDClj): 1.10 (s, 9 H); 4.07 (d, 2 H); 6.73 - 7.56 (m, 10 H); 9,30 (t, 1 H). c) 11-(tert,.-ButyIdiphenyIsilyloxy)-1-C4‘-(tert.-butyIdiphenyIsilyloxy)5, 58~dimethoxyphenyl3~undec-9Zen-1-ine 6.38 g product from example 27a and 3.13 g triphenylphosphine are reacted analogously to example 23c and 3.42 g resulting product are then reacted with 2.5 ml n-butyllithium solution and 0.90 g aldehyde shown in example 27b analogously to example 23d. Column chromatography with petroleum ether/ether (20:1) gives 1.74 g title compound. 1H~NMR (CDClj): 0.75 - 2.45 (m, 30 H); 3.33 (s, 6 H); 4.05 - 4.23 (m, 2 H); .13 - 5.63 (m, 2 H); 6.30 (s, 2 H); 6.97 - 7.67 (m, 20 H). d) 1 - (38,5-Di methoxy-48-hydroxypheny1)-11-hydroxy-undec-9Z-en-1-i ne Splitting off of the protective group from 1.71 g product obtained in example 27c with 12.9 ml of a solution of tetra-n-butylammonium fluoride in tetrahydrofuran (1 mol/l) analogously to example 14d gives, after column chromatography with petroleum ether/acetone (1:1), 0.625 g title compound, which melts at 74° - 76°C.

(CDClj): 0.95 - 2.50 (m, 13 H); 3.80 (s, 6 H); 3.93 0 4.23 (m, 2 H); .15 - 5.70 (m, 3 H); 6.50 (s, 2 H).

Claims

1. ) Phenol derivatives of the general, formula in which A and B are identical or different and each represent one of the groups -C=C-> cis-CH^CH- or trans-CH=CH“, R-j denotes hydrogen or a straight-chain alkyl radical with 1 to ό carbon atoms, or a 5“ to 7-membered cycloalkyl group, or a group of the formula -CCHgJ^-O-Ry, wherein m represents one of the numbers 1, 2 or 3 and Ry represents methyl or ethyl, or a group of the formula s wherein X represents a single bond, a -CHg- group or a -CHgO- group and Rg denotes a hydrogen, chlorine or fluorine atom or a methyl, methoxy or trifluoromethyl group and n represents one of the numbers 1 or 2, Rg represents hydrogen, methyl or ethyl, Rg denotes hydrogen or an acetyl or propionyl radical, r 4 represents hydrogen, an acetyl or propionyl radical or a straightchain or branched alkyl radical Rq with 1 to 4 carbon atoms, Rg represents a group of the formula -COOR-jq, wherein R-j θ is a hydrogen atom, a pharmaceutically tolerated cation, in particular a monovalent cation, a straight-chain or branched alkyl radical with 1 to ό catbon atoms or the group “(CH2)2^t^ CH 2^p“ CH 3^2‘ i ' p represents zero or one of the numbers 1 to 3, and of (sic) pharmaceutically tolerated salts of these basic esters with acids, or represents a group of the formula CO - N wherein R^ and R^ are identical or different and represent hydrogen, the alkyl radical R Q or 2-hydroxyethyl, or one of these radicals denotes a hydroxyl group and the other denotes hydrogen, or R-j-j and R-j 2 taken together represent the group -(Ci^q”? in which q represents one of the numbers 4, 5 or 6, or represents a group of the formula CO - N OR wherein R^ 3 represents hydrogen, -(d^lp-CH^, carboxymethyl, acetyl or propionyl and p in each case has the same meaning as above, or represents a group of the formula -C0MH“(CH2) r -M(CH 3 )2z wherein r represents one of the numbers 2 or 3, or pharmaceutically tolerated salts thereof with acids, or represents a group of the formula ©3 / \ - CO - Ν Y in which Y denotes an oxygen atom or the group )N-CH 3 , or if appropriate pharmaceutically tolerated salts thereof with acids, or represents a nitrile radical, or 5 represents a hydroxyl, acetoxy or propionyloxy group, an alkoxy group ORg, in which Rq has the same meaning as above, or - taken together with OR, - represents the methylenedioxy group and R^ represents hydrogen, a hydroxyl, acetoxy or propionyloxy group, the alkyl radical Rg or an alkoxy group ORg, wherein Rg in each case has the same meaning as above.

2. ) Phenol derivatives of the formula R„ R. C- c = C ORg 2^6 CSC—( wherein R-j to Rg and Rg and R^ have the same meaning as in claim 1. T wherein R-j to Rg and Rg and R& have the same meaning as in claim 1, 4) Phenol derivatives of the formula OH γ iti wherein R-j to Rg and Rg, R^ and A have the same meaning as in claim 1. 5) Phenol derivatives of the general formula 5 wherein R-j, R^ to R^, A and B have the same meaning as in claim 1. in which R-j denotes a hydrogen atom, a straight-chain alkyl radical with 1 to ό carbon atoms or a phenyl or cyclohexyl radical and R z to T 10 R,5 have the same meaning as in claim 1. 7) Phenol derivatives according to claims 1 to ό, in which R^ represents a hydrogen atom or a methoxy group. 8) Phenol derivatives according to claims 1 to 7, in which Rg represents one of the groups -OH, -0R o , -C0’CO-N / R 11 I \ R ' K 12 -CO-N OR or wherein R^, R-j-j to R-jg, P and V have the same meaning as in claim 1, β 5’ 9) Phenol derivatives according to claims 1 to 8, in which Rg represents one of the groups -OH, -OCHg or -CO-H '3 CH. 10) Medicament, characterized in that it contains as the active ingredient at least one of the phenol derivatives corresponding to claims 1 to 9 and is suitable for parenteral, oral, intranasal, percutaneous or rectal administration. 11) Medicament according to claim 10, characterized in that it contains as the active ingredient 0.01 to 50 mg of a phenol derivative corresponding to claims 1 to 9 per individual dose. 12) Medicament according to claims 10 and 11, characterized in that is is suitable for parenteral administration and contains 0.01 to 10 mg of a phenol derivative corresponding to claims 1 to 9. 13) Medicament according to claims 10 and 11, characterized in that it is suitable for oral administration and contains 0.1 to 50 mg of a phenol derivative corresponding to claims 1 to 9. 14) Medicament according to claim 13 for oral administration, characterized in that it is in the form of tablets, coated tablets or capsules, if appropriate with delayed release of the active ingredient. 15) Medicament according to claim 10 for intranasal, oral or peroral administration of a phenol derivative corresponding to claims 1 to 9 in spray form. 16) Medicament according to claim 10 for percutaneous administration, consisting of a reservoir which is to be applied to the skin and contains a phenol derivative corresponding to claims 1 to 9 in dissolved form, preferably with the addition of agents which promote penetration of the skin. 17) Process for the preparation of the medicaments according to claims 10 to 16, characterised in that the phenol derivatives corresponding to claims 1 to 9 are processed in the customary manner with excipient materials, solvents and/or diluents and if appropriate binders, tablet 5 disintegrating agents and other customary auxiliaries and the individual dosage forms are produced from the resulting mixture» 18) Process for the preparation of the phenol derivatives of the formula I from claim I, characterized in that A) a compound of the general formula II in which A, B, R-j and Rg have the same meaning as in formula I, R-j^ represents the alkyl radical Rq or a protective group which can be split off under mild conditions, R-jg represents the group OR-j^ or has the same meaning as Rg, with the proviso that in this radical 15 R-jq cannot represent a cation and the basic groups which may be present in Rg cannot be in salt form, or R-jg, taken together with the group OR-j^, represents a methy lenedi oxy group, R-j^ denotes a hydrogen atom or one of the groups Rq or OR-jand R-jy is a protective group which can be split off under mild conditions, is 20 prepared 1) by reaction of a compound of the formula ?2 ci OR C — C — Me ITT wherein R-j, Rg and R^y have the same meaning as above and Me represents a lithium, sodium or potassium atom or one of the radicals -MgBr or -Mgl, with a compound of the formula ^15 R 18 - (CH 9 ) r —ί Β V— iv in which B and R^z to have the same meaning as above and R-jg represents a bromine or an iodine atom, 5 at temperatures of about -80° to +75°C in an inert, aprotic solvent, if appropriate in the presence of catalytic amounts of a copper salt, or 2) by reaction of a compound of the formula IV, in which r 15 represents the group OR-jwith a compound or the formula k C ~C 1 OR,-, 1/ C - Me Ilia wherein R-j, R 2 and R^y have the same meaning as above and Me’ represents a lithium, sodium or potassium atom, in liquid ammonia at temperatures of about ~80°C to -35°C, or

3. ) by reaction of a compound of the formula in which A, R-j, R 2 , R under the conditions mentioned above for 1 or 2, or

4. ) (if the group A in the compound of the formula II represents 5 -CH=CH-) i) by treatment of a compound of the formula Rg R 1 — C — CHg — P (CgHg ) 3 — R ig 0R 17 VII in which R^, Rg and R^y have the same meaning as above and represents a chlorine, bromine or iodine atom, with a strong anhydrous base in inert solvents, and reaction of the phosphorane formed by splitting off HR^ 0 with an aldehyde of the formula i vii: wherein B and R^ to R^ have the same meaning as above, at temperatures of about -80°C to -5-3O°C, or ii) by reaction of the phosphorane formed by the action of a base on the compound of the formula IX wherein B, Rp to Rp and Rp have the same meaning as above, HR-jg being split off, with an aldehyde of the formula Rn .0 i 2 J's C — C ι \ 0R 17 h 5 wherein Rp R 2 and Rp have the same meaning as' above, at temperatures of about -80°C to +30°C in the presence of an inert solvent, or

5. ) Ci f the group B in the compound of the formula II represents -CH=CH~> 10 i) by reaction of a phosphorane formed from the compound of the formula ~?2 R, — C Ί ι OR. 1/ ( Ci V? ” P ^ C 6 H sb “ R 19 XI wherein A, Rp R?, Rp and Rp have the same meaning as above 15 by the action of a base and splitting off of HRp, with an aldehyde of the formula °v C - --/Rp -(/ 'VoRp XII ../ \ . Z a Si ^ R 16 wherein Rp to Rp have the same meaning as above at temperatures of about -80°C to +30°C in the presence of an inert solvent, or ii) by reaction of the phosphorane obtained by the action of a base on the compound of the formula XIII wherein R^ to and have the same meaning as above with an aldehyde of the formula r 2 R 1 “ f (CH 2 } 6 “ C 0R 17 XIV in which Az Rg and r 17 have the same meaning as above at temperatures of about ~80°C to +30°C in the presence of an inert solvent and the protective groups contained In R-j Z to Rqy are split off from the resulting compound of the formula II in a manner which is known per se and if appropriate - if at least one of the radicals R- and R z or Rg and R^ is to represent or contain an acetyl or propionyl radical - one or more acetyl or propionyl group(s) is/are introduced, or 0) 2 compound of the formula R i - f -Q OR 20 C Ξ0Η XV 7 1 wherein A, R-j and R 2 have the same meaning as above and R 2Q represents a hydrogen atom or has the same meaning as R^y is reacted, in the presence ot a secondary or tertiary amine which is liquid at about -10°C to +80°C and catalytic amounts of a complex palladium catalyst and if appropriate catalytic amounts of copper(I) iodide at about 0°C to 75°C, with a compound of the formula wherein R^g has the same meaning as above, R 2 ^ denotes a hydrogen atom, the alkyl radical R9 a protective group which can be split off under mild conditions, R 22 represents the group OR 2 -j or has the same meaning as Rg, with the proviso that in this radical R<,g cannot represent a cation and the basic groups which may be present in Rg cannot be in salt form, or R 22 , taken together with the group OR 2 -j, represents a methylenedioxy group and R 23 has the same meaning as R^ or represents a hydroxyl group, and if appropriate - if at least one of the radicals Rg and R^ or Rg and R^ is to represent or contain an acetyl or propionyl radical - one or more acetyl or propionyl group(s) is/are introduced, or a compound of the formula wherein Me, B and R^ to R-j^ have the same meaning as above. is reacted in the presence of an inert solvent at about -80°C to *30°C with a compound of the formula / R 2 Vl aJ R„ in which R-j and Rg have the same meaning as above to give a compound of the formula wherein A, B, R-j, Rg and R^z to R-j^ have the same meaning as above and the protective groups contained, if appropriate, in R-j^ to R^ are split off from the reaction product and - if at least one of the radicals Rg and Rz or Rg and R^ is to represent or contain an acetyl or propionyl radical ~ one or more acetyl or propionyl groups is/are introduced, or D) a compound of the formula t XXI in which A, δ and R-j^ to R-j^ have the same meaning as above and RJj 7 3 has the same meaning as with the exception of hydrogen, is prepared 1) by treatment of a compound of the formula i CH 3(CH 2 ) p -Q3 2 - p - CH 2 - C - RJ 0 0 XXII wherein p and RJg have the same meaning as above, with an anhydrous base in an inert solvent and subsequent reaction with a compound of the formula VIII at temperatures of about -10°C to +35°C, or 1q 2) by reaction of a compound of the formula XXIII in which B and R-gz to R-gg have the same meaning as above, in the presence of a tertiary amine with a boiling point above about Ί·80°ε and catalytic amounts of a complex palladium catalyst and if appropriate catalytic amounts of copper(I) iodide at about 0°C to 75°C, with a compound of the formula R ,9“S- R i XXIV wherein and have the same meaning as above, and this compound of the formula XXI is converted into the corresponding compound of the formula I (in which and if Γ; A <*3 appropriate R 2 ars ot ^ er than hydrogen) by reduction with a metal borohydride or by reaction with a compound of the formula R 2 -Me, wherein Me has the same meaning as above and R 2 has the same meaning as R 2 , with the exception of hydrogen, subsequent splitting off of protective groups present in R^ to R-j^ and if appropriate if at least one of the radicals Rj and R^ or Rj and R^ is to represent or contain an acetyl or propionyl radical introduction of one or more acetyl or propionyl groups, and the radicals Rj and R-^ or R 22 in the compounds obtained according to A, B, C or D are converted into the desired group Rj and/or if appropriate triple bonds present therein are hydrogenated catalytically to give double bonds. 19) Process according to claim 18, characterized in that the protective groups represented by R^, R<| 2 , R 2 g or R 2 22 are identical or different representatives from the group comprising the tetrahydropyran-2-yl radical, the tert.-butyldi methylsi lyl radical and the tert.-butyldiphenylsilyl radical. 20) Process according to claims 18 and 19, characterized in that procedures Al and A3 are carried out in the presence of a dipolar aprotic solvent and a copper(I) salt. 21) Process according to claims 18 and 19, characterized in that nbutyllithium, potassium tert.-butylate or sodium bis~(trimethylsiLyl)— amide is employed as the anhydrous base for the phosphorane formation by splitting off HR^ in procedures A4 and Α5» 22) Process according to claims 18 and 19, characterized in that bis(triphenylphosphine)-palladium(II) chloride or acetate or tetrakis(triphenylphosphine)-palladium are employed as the complex palladium catalyst in procedures B and D 2 and these procedures are carried out in the presence of a trialkylamine with 2 or 3 carbon atoms in each of the alkyl radicals. 7 5 with a compound of formula ϊ in which Rg represents a) an esterified carboxylic group -COOR^q wherein R^ is the alkyl group R g or the group -(GH^) 2 ~Nt(CHg) p ~CH 3 ] 2s or b) an unsubstituted carboxylic group COOH, said reaction being 5 performed in presence of an agent capable to split off water, or with an intermediately formed reactive functional derivative of the carboxylic group, 23 )A phenol derivative of the general formula I given and defined in claim 1 or a pharmaceutically acceptable 10 acid addition salt thereof f substantially as hereinbefore described with particular reference to the accompanying Examples . 24 )A process for the preparation of a phenol derivative of the general formula I given and defined in claim 1 15 or a pharmaceutically acceptable acid addition salt thereof, substantially as hereinbefore described with particular reference to the accompanying Examples. 25) A phenol derivative of the general formula I given and defined in claim 1 or a pharmaceutically acceptable 20 acid addition salt thereof, whenever prepared by a process claimed in a preceding claim. 26) A medicament according to claim 10,, substantially as hereinbefore described.