CS203066B2 - Process for preparing new derivatives of anhydrofuranose - Google Patents

Description

The present invention relates to a process for the preparation of novel anhydrofuranose derivatives of the general formula I

CH-A-O-CH

LIQUID ₃ ~ LIQUID (I) where

R 2 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 aminoalkyl, C 1 -C 4 alkenyl, C 1 -C 2 phenylalkyl or C 1 -C 4 alkanoyl optionally a hydroxyl group or a (C 1 -C 4) alkanoyloxy group or a halogen substituted benzoyl or naphthoyl group, a (C 1 -C 4) alkylsulfonyl group, a toluenesulfonyl, a pyridylcarbamoyl group, a (C 1 -C 4) alkylcarbamoyl group or a phenylcarbamoyl group;

R 3 represents hydrogen, alkyl or alkenyl of 1 to 4 carbon atoms, optionally hydroxy or C 1 -C 4 alkanoyl or halogen substituted benzoyl or C 1 -C 4 alkanoyl or optionally halogen substituted phenylalkyl of 1 or 2 carbon atoms in the alkyl moiety and the group -A-O- is a radical of the formula -CHOR5-CH2-O- or -CH2CH5-OR-) in which R5 and R6, respectively, have one of the meanings given for R5, or wherein --CH 2 OR 6 represents hydrogen, or wherein two of the radicals

R @ 2, R @ 3 and R @ 8 and / or R @ 6 taken together are C1 -C4 alkylidene or phenylalkylidene, one of the radicals

R 2, R 3 and R 5 and R 6, respectively, have a meaning other than hydrogen, and wherein in the compounds with the group -CHOR 5 -CH 2 -O- in the meaning of the group "A-O" one of the radicals

R 2, R 3 and R 5 are other than methyl when the other two of these are methyl and wherein, in the compounds with the group -CHOR 5 -CH 2 -O, one of the radicals -A-O-, is one of the radicals

R 2, R 3 and R 5 for the meaning of -A-O- are other than acetyl, when the other two of these are acetyl, and wherein in the compounds with the group -CH 2 CH 2 OR 1 -O-, for the meaning of -A-O-, one is one of residues

R2, R5 and R6 are other than benzyl when the other two of these are benzyl, and salts thereof.

Suitable lower radicals are, in particular, radicals having up to 4 carbon atoms. An aliphatic residue is a residue whose free bond results from an atom that is not a member of the aromatic system.

Unless otherwise stated below, each group has the number of carbon atoms in the chain equal to the number of atoms given in Formula I.

The novel anhydrofuranose dervates of the formula I are derivatives of 1,5-anhydro-L- or D-hexafuranose or 1,6-anhydro-L- or -D-hexafuranose, in particular 1,6-anhydro-1-D-glucofuranose derivatives. 1,6-anhydro-β-D-allofuranose, 1,6-anhydro-β-D-mannophthyranose and 1,6-anhydro-α-L-ido ^; furanose, 1,6-anhydro-.alpha.-L-gulose or the corresponding derivatives of 1,5-an, hydroxylofuranos.

In particular, the alkyl group R ²¹ , R 3 and / or R 5 or R 8 is, for example, ethyl, isopropyl, straight or branched and in any position bonded butyl and especially methyl or n-propyl.

Aminoalkyl R2 is preferably a group in which the amino group can be a free amino group, a lower alkylamino group or a lower dialkylamino group, such as 2-methylaminoethyl, 2-dimethylaminoethyl, 2-ethylaminoethyl and especially 2-diethylaminoethyl.

The alkenyl group R @ 2, R @ 3 and / or R @ 5 and R @ 8 in particular are, for example, isopropenyl, 2-methallyl, 3-butenyl and especially allyl.

Halogen is, for example, bromine and especially chlorine.

In particular, the alkyl group has the meaning given for R2, R3 and / or R6 and R6, respectively.

The alkoxy group is especially one in which the lower alkyl moiety has the meanings given for R2, R3 and / or R6 or R6, as is the case for the ethoxy, n-propoxy, isopropoxy or especially the methoxy groups.

The acyl radical R @ 2, R @ 3 and / or R @ 5 and R @ 6 respectively is in particular an acyl radical of an organic acid and in particular an organic carboxylic acid radical. The acyl radical may in particular be an alkanoyl group, in particular a lower alkanoyl group such as acetyl or propionyl, or also an aroyl radical such as 1-naphthoyl or 2-niaphtoyl, in particular benzoyl optionally substituted by halogen, lower alkyl , lower alkoxy, trifluoro, methyl, hydroxyl or lower alkanoyloxy, such as salicyloyl or acetylsalicyloyl, as well as pyridylcarboxylic, such as nicotinoyl, or it may also be an acyl radical of an organic sulfonic acid such as alkanesulfonic acid especially lower alkanesulfonic acids, such as methanesulfonic or ethanesulfonic acid, or aryisulfonic acid residue, especially phenylsulfonic acid, optionally substituted by a lower alkyl group such as benzenesulfonic acid or acid p-toluenesulfonic acid as well as carbamoyl radical, either unsubstituted or lower alkylcarbamoyl or arylcarbamoyl radical such as methylcarbamoyl or phenylcarbamoyl.

Ylidene radical of two radicals R 2, R 3 and R 5 or R 8 is especially a ylidene group such as an alkylidene group, for example a methylidene, ethylidene or especially isopropylidene group, or an arylalkylidene group such as a phenylalkylidene group wherein the phenyl moiety is optionally substituted with an alkyl group , alkoxy, halogen and / or trifluoromethyl, and in particular benzylidene.

Preferably, all of the foregoing and subsequent compounds of the anhydrofuranose derivative type are 1,6-anbydrO '- (S-D-glucoifuranose) derivatives.

The new compounds have valuable farm, cological properties.

The anhydrofuran derivatives according to the invention are particularly characterized by fibrinotytic and thrombolytic effects, as can be shown in animal experiments, for example by oral administration of about 10 to 200 mg / kg, in particular about 10 to 100 mg / kg to rats. The fibrinolytic and thrombolytic effect is demonstrated in an experiment corresponding to the publication by M. Růegg, L. Riesteter and R. Jacques in Pharmacology 4, 242-254 (1970) by reducing the dissolution time of the euglobulin clot.

Among the compounds of formula I, those particularly preferred are those wherein the group —A — O — represents a radical of formula

-OHOR 5 -OHa-O-, and R a, R 3 and R 5 are each independently hydrogen, alkyl, alkenyl, benzyl, halobenzyl, alkanoyl, benzoyl, halobenzoyl, hydroxybenzoyl, alkanoyloxybenzoyl, or pyridylcarbonyl, or two of R 2, R 3 and R 5 are alkylidene or benzylidene, one of R 2, R 5 and R 5 being different from hydrogen when the other two are hydrogen, and one of R 2, R 3 and R 5 is not methyl when the other two are methyl, and wherein one of the radicals R 2, R 5 and R 5 is not an acetyl group if the other two of these radicals are an acetyl group.

In particular, compounds within the scope of formula (I) wherein -A-O'- is a radical of formula -CHOR 5 -CHa-O,

R @ 2 represents hydrogen, C1 -C6 alkyl, dialkylaminoalkyl with all alkyl radicals together of up to 7 carbon atoms, benzyl, chlorobenzyl, lower alkanoyl of 2 to carbon atoms, benzoyl, o-hydroxybenzyl, o-alkanoyloxybenzoyl of 2 up to 4 carbon atoms in the o-alkanoyloxy moiety, naphthoyl, alkylcarbamoyl of up to 4 carbon atoms, phenylcarbamoyl, alkylsulfonyl of 1 to 3 carbon atoms, toluylsulfonyl or pyridylcarbonyl, and R 3 and R 5 are each independently hydrogen, alkyl of 1 to 3 carbon atoms, benzyl, chlorobenzyl or -benzoyl, wherein one of R2, R3 and R5 is other than hydrogen when the other two are hydrogen, and wherein one of R2, R3 and R5 is not acetyl if the other two of these residues are acetyl.

Particularly suitable are compounds within the scope of formula (I) wherein -A-O- is a radical of formula -CHOR 5 -CHa-O-,

R2 is C2 -C4 alkanoyl, benzoyl, o-hydroxybenzoyl, o-alkanoyloxybenzoyl of 2 to 4 carbon atoms in the o-alkanoyloxy moiety, naphthoyl or pyridylcarbonyl, and R3 and R5 are each independently hydrogen, lower alkyl with 2 or 3 carbon atoms, benzyl, chloro benzyl, benzoyl or o-hydroxybenzoyl.

Particularly suitable are compounds within the scope of the compounds of formula (I) wherein the group —A — O — represents a radical of the formula —CHOR 5 —CHa —O—,

R 2 is hydrogen, and R 3 and R 5 are each independently C 1 -C 3 alkyl, allyl, methallyl, benzyl or chlorobenzyl.

In particular, compounds of formula (I) wherein the group "A-O" is a radical of the formula -CHOR 5 -CH a -O,

R 2 is hydrogen, C 2 -C 4 lower alkanoyl, benzoyl, o -hydroxybenzoyl, o-acetoxyhenzoyl, naphthoyl or pyridylcarbonyl, and R 3 and R 5 are each independently C 1 -C 3 lower alkyl, benzyl, chlorobenzyl, benzoyl, o-hydroxybenzoyl, o-acetoxybenzoyl or naphthoyl group.

Particular mention should be made of the compounds as described in the examples, and in particular 1,6-anhydro-3,5-di-O-benzoyl-2-O-nicotinoyl-4-D-glucofuranose, 1,6-anhydro-1-ol. 2-O-benzoyl-3, ^{5-di-0-benzyl-} / 3-D-glucofuranose, 1,6-aohydro 3,5-di-0-benzyl- / 3-D-allofuranosu, l, 6 2-O-benzoyl-3,5-O-benzyl-5-D-allofuranose, 6-ihydro-3,5-di-O-benzyl-5-glucofuranose.

The novel compounds can be prepared using known methods by treatment with a compound of formula VII by acid or base

CH - A - O - CH ₃ h - ₃ - CHOR _Z (V) where

A, R 2 and R 3 have the meanings given above and one of the general symbols

X1 and X2 are each a reactively esterified or etherified hydroxyl group and, if desired, the substituents are introduced, varied and / or cleaved into the compounds obtained, and / or the racemate mixtures obtained are separated into the pure racemates and / or the racemates obtained. they are resolved into optical antipodes and / or the obtained salts are converted into free compounds or other salts, or the obtained free compounds are converted into their salts.

The reactively etherified hydroxyl group is preferably an arylmethoxy group, such as a lower alkylbenzyloxy group, a lower alkoxybenzyloxy group, a halobenzyloxy group, and in particular a benzyloxy group.

Xz is furthermore an acyloxy group such as an alkanoyloxy group such as a lower alkanoyloxy group such as a propionyloxy group or particularly an acetoxyl group, as well as an aroyloxy group such as a lower alkylbenzoyloxy group such as a methylbenzoyloxy group, a lower alkoxybenzoyloxy group, e.g. a group such as a chlorobenzoylcyl group, or in particular a benzoyloxy group.

The reactive etherified hydroxyl group is in particular a halogen atom such as fluorine, chlorine, bromine or iodine. Further, a reactive esterified hydroxyl group is a hydroxyl group esterified with a strong inorganic or organic acid, such as sulfuric acid or an organic sulfonic acid, for example benzenesulfonic acid, 4-bromobenzenesulfonic acid, 4-toluenesulfonic acid, lower alkanesulfonic acid, for example methanesulfonic acid or ethanesulfonic acid. Thus, X 1 is especially benzenesulfonyloxy, 4-bromohenzenesulfonyloxy, 4-toluenesulfonyloxy, methanesulfonyloxy or ethanesulfonyloxy.

The reaction of a compound of formula V with an acid or base is carried out, in particular, using a Lewis acid, a strong inorganic acid or an inorganic or organic base.

Lewis acids are electron acceptors. For example, they are those in which one atom contains less electrons than the fully contained octet, such as a lower boron trialkyl derivative, for example trimethylboron, or especially such as boron trihalides such as boron trifluoride, boron trichloride or boron tribromide. Suitable Lewis acids are also metal halides in which the central atom can receive more than 8 external electrons, such as titanium tetrahalides, niobium pentahalides or tantalum pentahalides, for example titanium tetrachloride, niobium chloride or tantalum tetrachloride, in particular tin, zinc dihalides and very particularly tin tetrahalides such as tin (II) chloride, zinc (II) chloride and especially tin (II) chloride.

Suitable strong inorganic acids are, for example, hydrohalic acids, in particular hydrofluoric acid.

Suitable inorganic bases are, in particular, alkali metal or caustic earth metal hydroxides, or the corresponding carbonates or acidic carbonates, such as sodium hydroxide, potassium hydroxide, or in particular harium hydroxide or sodium bicarbonate. Suitable organic bases are, in particular, alkali metal alcoholates such as alkali metal lower alkanolates, for example sodium ethylate, potassium tert-butoxide or, in particular, sodium methylate, as well as nitrogenous bases such as especially spherically hindered nitrogenous bases, for example tertiary amines or quaternary ammonium salts of tertiary amines such as lower trialkylamines, for example triethylamine or especially trimethylamine, or lower trialkylammonium halides, for example triethylammonium bromide or especially trimethylammonium bromide, or also aromatic nitrogen heterocycles such as quinoline or pyridine,

They are compounds of the general formula

Where one of the radicals X 1 and X 2 is a hydroxyl group and the other one is a halogen, the reaction can be carried out preferably by treatment with an acid or a base.

When X 1 is a hydroxyl group and X 2 is a halogen, suitable acids are, for example, hydrofluoric acid or especially Lewis acids, and suitable bases are, for example, spherically hindered organic nitrogen bases. When X1 is halogen and Xa is hydroxyl, suitable acids are, for example, hydrofluoric acid or, in particular, Lewis acids, and suitable bases are, for example, inorganic or organic bases.

When X1 is a residue cleavable leaving a negatively charged oxygen atom in the molecule, and Xa is a residue cleavable to form a carbonium ion, the reaction is preferably carried out by treatment with acids such as strong inorganic acids or Lewis acids. The reaction may be carried out in a known manner under cooling, for example at about -10 to + 10%, or at room temperature, i.e. at about + 20%. To accelerate the reaction, the reaction mixture may be slightly heated, for example, to about 40%. The reaction is preferably carried out in a solvent, preferably a halogenated hydrocarbon derivative, such as halogenated lower alkane derivatives, for example methylene chloride, chloroform or especially dichloroethane, or else aromatic hydrocarbons such as toluene or xylene, preferably with the exclusion of water.

If X 1 is a residue cleavable to form a carbonium ion, which is generally formed by inversion at / the carbon atom to which X 1 is bound, and if X a is a residue cleavable leaving a negatively charged oxygen atom in the molecule, the reaction is carried out preferably by treatment with bases, such as inorganic or organic bases, especially with alkali metal alcoholates. The reaction can be carried out in a known manner under cooling, for example at -10 to + 10% or at room temperature, i.e. at about + 20%. To accelerate the reaction, the reaction mixture can also be slightly heated, for example to about 40 to 60%. The reaction is preferably carried out in a solvent, most preferably water, and in alcohols such as lower alkanols, for example methanol or ethanol, or ethers, such as dimethyl ether, dioxane or tetrahydrofuran, or acetone.

In the compounds obtained, substituents may be introduced or cleaved in the customary manner in the customary manner, or the compounds can be cleaved off, or the compounds obtained can be converted in conventional manner into other end products.

Thus, in compounds containing at least one free hydroxyl group, this group can be converted to form a substance containing a residue other than R 2, R 3, R 5 or R 8, especially as described above.

Further, compounds containing at least one alkenyl radical R 2, R 3, R 5 or R 6 can be hydrogenated, for example with hydrogen in the presence of a catalyst, such as hydrogen in the presence of a palladium or platinum catalyst. In this case, groups which can be removed by hydrogenolytic cleavage can be simultaneously removed.

Further, in compounds containing at least one cleavable residue, it can be cleaved off. Thus, especially in compounds containing a solvolysable residue, such a residue can be cleaved solvolytically, for example, hydrolytically or alcohololytically. The hydrolytically or alcohololytically cleavable radical is, for example, an ylidene radical which is formed together of two radicals R @ 2, R @ 3 and R @ 5 and R @ 6 respectively and which is cleaved off under gentle conditions in a conventional manner by water or an alcohol such as a lower alkanol such as methanol or ethanol in the presence of an acid, for example inorganic, such as one of the hydrohalic acids, such as hydrochloric acid, or by treatment with an organic acid, such as one of the carboxylic acids or dicarboxylic acids, such as acetic acid or sulfonic acids, such as p-toluenesulfonic acid . Said cleavage is preferably carried out in the presence of a diluent, whereby one reactant, for example an alkaline reagent or an organic acid such as acetic acid, can simultaneously serve as a diluent. Mixtures of solvents and diluents may also be used. If alcohol is used, it is preferably carried out in the presence of a hydrohalic acid, in particular hydrochloric acid, and if water is used, it is preferably carried out in the presence of an organic carboxylic acid, in particular formic or oxalic acid, and particularly in the presence of acetic acid. the reaction is carried out, if necessary, with cooling, but primarily at room or elevated temperature (e.g. at about 25 to 150 ^° C), optionally in a closed vessel under pressure and / or in an inert gas environment, such as nitrogen atmosphere. When an alcohol in the presence of an anhydrous acid, especially hydrogen chloride, is used as the reagent in the abovementioned cleavage reactions, one of the two hydroxy groups together etherified by the formation of the ylidene moiety can be etherified as it is released. The cleavage reaction can therefore be used simultaneously to introduce an etherified hydroxyl group into a compound obtainable according to the invention.

In the compound obtained and the acyl radical with a cleavable group, in particular hydroxyl groups etherified with an optionally substituted ¹ benzyl radical, or in the case of a benzylidenedioxyl radical, such a radical can be converted to a hydroxyl group according to known methods, for example by treatment with hydrogen at birth or catalytically activated. hydrogen in the presence of a noble metal catalyst such as a palladium catalyst.

In the compound obtained and the acyl radical R @ 2, R @ 3 and / or R @ 6 and / or R @ 6, the acyloxy group can be converted to a hydroxyl group, for example by hydrolysis or alcoholysis, preferably in the presence of a slightly basic reagent such as some acid alkali metal carbonates. In this case, the hydroxyl group can be liberated, possibly even during cleavage of the ylidene residue, for example in the reaction of the corresponding compound with an alcohol in the presence of an acid.

When water in the presence of an acid is used to cleave the ylidene residue, both hydroxyl groups etherified with such a group are obtained in free form. The esterified hydroxyl group can be converted to its esterified hydroxyl group.

In the obtained acyl compound. the radical R @ 2, R @ 3 and / or R @ 5 and / or R @ 6 can be converted to an alkyl, alkenyl or arylalkyl radical in a conventional manner. This conversion to the correspondingly ether-hydroxyl scurf is preferably carried out by reacting the starting material with a correspondingly reactively esterified alcohol derivative, for example as mentioned hereinbefore. In this case, the reaction of the acyloxy groups of the starting material is preferably carried out in the presence of an acid, in particular a mineral acid, such as. hydrohalic acids, for example hydrochloric acid or, in particular, in reaction with a reactive esterified alcohol in the presence of a suitable acid binder such as silver, lead or mercury, or in the presence of the corresponding oxide or tertiary base, alcohol and metal derivatives may also be used , such as the corresponding alkali metal compounds, for example sodium or potassium, of the caustic earth metals, such as magnesium, net in the presence of silver compounds. An ion exchange resin may also be used in place of the acid. This reaction is preferably carried out in the presence of a solvent, and alcoholic reagents may also be used as such.

The compounds with basic groups can be obtained in the form of acid addition salts with acids, in particular pharmaceutically usable, forming non-toxic salts, for example with inorganic acids such as hydrochloric, hydrobromic, sulfuric or sulfuric acids. phosphoric acid, or with organic acids such as aliphatic, cycloialiphatic, cycloaliphatic-aliphatic, aromatic, araliphatic, heterocyclic or heterooylic-aliphatic, carboxylic or sulfonic acids such as acetic, propionic, succinic, glycolic, lactic, malic, tartaric, citric, ascorbic, maleic, phenylacetoacetic, benzoic, 4-aminobenzyl, anthranilic, 4-hydroxybenzoic, salicylic, aminosalicylic, embonic or nicotinic, as well as methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, p-toluenesulfonic acid, p-toluenesulfonic acid, p-toluenesulfonic acid, sulfanil or cyclohexylsulfamate. Salts of this type can be obtained, for example, from free compounds containing basic groups, by reaction with acids or with suitable anion exchange resins.

In view of the close relationships between the novel compounds in free form and in the form of the corresponding salts, in the foregoing and in the following description, the terms free compounds or salts and possibly corresponding salts or free compounds are meant wherever this would make sense and wherever expedient.

The novel compounds can be obtained as mixtures of isomers, such as racemates or diastereoisomeric mixtures, or in the form of pure isomers, such as optically active ingredients. The separation of the obtained isomer mixtures into the pure isomers is carried out according to known methods. Racemates can be separated into optical antipodes, for example by physicochemical differences, such as solubility differences, differences in diastereoisomeric salt properties, or by fractional crystallization from an optically active solvent, or by chromatography, especially on thin layers, on an optically active carrier on which division into optical antipodes. In this case, preferably the pharmacologically more active or less toxic pure isomer, in particular the more active or less toxic, of the two active antipodes is isolated.

The above processes can be carried out using known methods, without solvents or preferably in the presence of diluents or solvents, if necessary, with cooling or heating, under elevated pressure and / or in an inert gas environment such as nitrogen atmosphere.

In view of all the substituents in the molecule, if desired, especially in the presence of readily hydrolyzable O-acyl residues, particularly gentle reaction conditions such as short reaction times, the use of slightly acidic or basic bases at low concentrations, stoichiometric ratios of amounts to each other, suitable catalysts, solvents, temperature and / or pressure conditions.

The invention also relates to those forms of the process, when n CH ^F starts from a compound obtainable in any desired process stage as an intermediate and the remaining process steps are carried out with pressure compound or process at any stage interrupts or- starting compound formed under the reaction conditions or used in the form of a reactive derivative or salt. In this connection, it is preferable to use starting materials from which the compounds of the invention which are particularly valuable are obtained in the process according to the invention.

The starting materials are known or can be prepared using known methods.

The invention further relates to pharmaceutical compositions comprising an anhydrofuranose derivative of the formula I, wherein R 2 and R 3 independently of one another are hydrogen, alkyl, alkenyl, arylalkyl or acyl, and the group "A-O" represents a radical of the formula -GHOR 5 -CH 2 -O - or —OH (CH2OR6j-O-), wherein R5 and R6, respectively, have the meanings indicated for R2, or wherein two of the radicals R2, R3 and R5 or R6 together represent an ylidene radical.

Preferred pharmaceutical compositions are those containing an anhydrofuranose derivative within the range of the aforementioned compounds, or the individual compound as such.

The pharmaceutical compositions of the invention preferably contain an effective amount of the active ingredient together or in admixture with inorganic or organic, solid or liquid, pharmaceutically acceptable carriers which are suitable for enteral, parenteral or topical administration. Suitable compounds for their preparation are those which do not react with anhydrofuranos derivatives, such as water, gelatin, lactose, starches, stearyl alcohol, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, propyleinglycols, vaseline or other known drug carriers. The pharmaceutical preparations may be, for example, tablets, dragees, capsules, suppositories, creams, ointments, or, in liquid form, solutions (e.g. elixirs or syrups), suspensions or emulsions. The pharmaceutical preparations may be sterilized and / or. they may contain adjuvants such as preservatives, stabilizers, wetting agents and / or emulsifiers, solubility enhancers, salts for adjusting the osmotic pressure and / or buffers. Said pharmaceutical preparations may contain, if desired, other pharmaceutically valuable substances, prepared by conventional methods, for example using conventional methods of mixing, granulating or dragee-forming. They contain about 0.1 to 75%, in particular about 1 and 50%, of the active ingredient.

The invention further relates to the treatment of warm-blooded individuals to achieve fibrinolytic, thrombolytic and / or anti-inflammatory effects by administering a pharmaceutical composition of the invention. The daily dose preferably contains about 50 to 500 milligrams, preferably about 100 to 300 mg of active ingredient in a warm-blooded individual weighing 70 kg.

Further examples describe the process of the invention in more detail. Temperature values are given in degrees Celsius.

Example 1

To a solution of 950 mg of 10-acetyl-2-O-allyl-3,6-di-O-benzyl-4-O-mesyl-α-D-glucopyranose in 10 ml of Ν, Ν-dimethylformamide was added 390 mg of sodium azide and heated with stirring. 1.5 hours at 120 ^DEG C. the mixture was cooled and 50 mL of water. It is extracted with ether and the organic phase is washed three times with water, dried over magnesium sulphate, filtered and evaporated to dryness. The residue is purified by chromatography on 10 g of silica gel with ether: petroleum ether (1: 1) as the mobile phase. As a colorless oil gave 1,5-anhydro-i2-O-allyl-3,6-di-O-benzyl - «- D-galaktofuranc is, _Rf value amounts to 0.52 (silica gel) in the system ether / petroleum ether 2: 1.

[ _.alpha. ] _{D @} ²⁰ = + 62 DEG. + -. 1 DEG (chloroform, c = 1.306).

Example 2 ^;

The following compounds are obtained in an analogous manner:

1. 2-O-acetyl-1,6-anhydro-3,5-di-O-benzyl-α-D-glucofuranose, [ _.alpha. ] _D @ ²⁰ = -20.6 DEG (chloroform);

2. 1,6-anhydro-3,5-di-O-heinzyl-5S-D-glucofuranose, m.p. 112-113 ° C;

3. 1,6-anhydro-3-O-benzyl- [3-D-glucO 'furanose, m.p. 102-103 ° C;

4. 1,6-anhydro-3,5-di-O-benzyl-β-D-mannofuranose, m.p. 117-119;

5th 2-O-acetyl-6-anhydrO'-Ob-5-O-benzyl-3-O-methyl-AS-D-glycofuranose is obtained, _Rf = 0.23 (thin layer chromatography on silica gel) cyclohexane ethyl acetate (2: 1),

6. 1,5-anhydro-5-O-benzyl-3-O-ethyl- [beta] -D-glucofuranose, [ _.alpha. ] _D @ ²⁰ = -8 DEG. + -. 1 DEG (chloroform);

7. 2-O-acetyl-6-Anhydro-5-O-benzyl-3-O-n-proipyl-.beta.-D-glycofuranose is obtained, _Rf = 0.30 (thin layer chromatography on silica gel) cyclohexane and ethyl acetate (2: 1),

8. 2-O-acetyl-1,6-anhydro-5-O-p-chlorobenzyl-5-O-n-propyl-β-D-glucofuranose, yellowish oil,

9. 1,6-anhydro-5-O-p-chlorobenzyl-3-O-n-propyl-4-D-glucofuranose, clear yellowish oil,

10. 1,6-anhydro-2-O-methyl-3,5-di-On-propyl-.beta.-.beta.-β-glycolophenyl, [.alpha.] _D @ ²⁰ = + 15 DEG. + -. 1 DEG (chloroform);

11. 1,6-anhydro-3,5-di-O-methyl-β-D-glucofuranose, boiling point 140-150 ° (external temperature), 7 Pa,

12. 1,6-anhydro-2-O-methyl-3,5-di-O-n-propyl-4-D-glucofuranose, colorless oil, boiling point 90-100 ° (external temperature), 5 Pa,

13. 1,6-anhydro-2-O-methyl-3,5-dl-O-n-propyl-β-D-glucofuranose, colorless oil, boiling point 90-100 ° (external temperature), 5 Pa,

14. 1,5-anhydro-2-O-methyl-3-O-n-propyl-β-D-xylofuranose, boiling point 45 °, 27 Pa,

15. 1,5-anhydro-2-O-benzyl-3-O-n-propyl- [beta] -D-xylofuranose, boiling point 110 DEG, 13 Pa,

16. 1,6-anhydro-2,3,5-tri-O-benzoyl- [S-D-allofuranose], m.p. 163-165 °; and

17. 1,6-Anhydro-2,3,5-tri-O-benzoyl-5-D-glucofuranose, m.p. 138-140 °.

Example 3

22.6 g of syrupy 2-O-acetyl-1,6-anhydro-3,5-di-O-henzyl-5-D-glucofuranose is stirred in a solution of 0.5 g of potassium carbonate in 400 ml of methanol for 15 hours, temperature of about 20 °. The reaction mixture was evaporated, the residue was dissolved in ether and the ether solution was washed with water. After drying, filtering and concentrating the ether solution, a syrup is obtained which crystallizes by adding ether. Double crystallization from ether at -15 ° or from ether to cyclohexane 1: 1 gives 1,6-anhydro-3,5-di-O-benzyl- [beta] -D-glucofuranoe as crystals of m.p. 112 DEG-113 DEG and [.alpha.] D @ ²⁰ = -8.7 DEG (chloroform). Chromatography of the inert liquor on silica gel using cyclohexane / ethyl acetate 1: 1 gives additional 1,6-anhydro-3,5-di-O-benzyl-β-D-glucofuran furan -axes in crystalline form.

Example 4

1.6 gL, 6-anhydro-3,5-dl-O-benzyl- [beta] -D-glucofuranose are hydrogenated in 70 ml of methanol in the presence of 300 mg of 5% palladium on carbon at normal pressure. After 10 hours, the starting material largely disappeared (as determined by thin layer chromatography on silica gel in chloroform: aceto-n = 9: 1). The catalyst is filtered off, the filtrate is evaporated to dryness and the residue is chromatographed on 40 g of silica gel with chloroform / acetone 9: 1. There was thus obtained 1,6-anhydro-3-O-benzyl- [beta] -D-glucofuranose as colorless crystals of m.p. 102 DEG-103 DEG and [ _.alpha. ] _D @ ²⁰ = + 23.1 DEG (water).

2030Θ6

1S

Example d 5

A solution of 3.72 g of nicotinic acid chloride in 10 ml of pyridine is added dropwise at about 25 DEG to a solution of 6 .gamma., 6-anhydro-3,5-dl-O-benzyl-.beta.-D-glucofuranose in 15 ml of pyridine. After standing at 25 ° for 1 hour, the reaction mixture was partitioned between water and ether, the ether phase was washed with sodium bicarbonate solution and water to pH 7, then dried over sodium sulfate, and evaporated in vacuo followed by crystallization from chloroform / petroleum ether. 98 DEG-100 DEG and [.alpha.] _{D @} ²⁰ = + 13.6 DEG (chloroform). A further fraction of 1,6-anhydro-3,5-dl-O-benzyl-2-O-nicotinoyl- [beta] -D-glucofuranose is obtained from the mother liquors. Example 6

To a solution of 7 g of 1,6-anhydro-3,5-di-O-benzyl-4-D-glucofuranose in 30 ml of absolute dimethylsulfoxide was added 2.7 g of powdered potassium hydroxide, followed by dropwise addition. 5.2 g (4.7 ml) of benzyl chloride. After the reaction subsided, the reaction mixture was allowed to stand

1.5 hours at about 25 °. The reaction solution is evaporated in vacuo, taken up in ether and water, the ether phase is separated and washed with water until neutral. Drying and concentration gave an oil which was chromatographed on 200 g of silica gel. Drying in vacuo at 1 Pa affords a colorless oil which slowly crystallizes. The substance has a melting point of 50-55 ° and [α] _D ²⁰ = + 8.3 ° (chloroform) and is 1,6-anhydro-2,3,5-tri-O-benzyl- β-D-glucO 'furanosu. Example 7

To a solution of 7-gl, 6-anhydro-3,5-di-O-benzyl-5-D-glucofuranose and 1.42 g of powdered potassium hydroxide in 30 ml of absolute dimethylsulfoxide was added dropwise 2.61 g (2.05 ml) of dimethylsulfate. . After 2 and 4 hours at 253 an additional portion of 1.42 g of potassium hydroxide and 2.05 ml of dimethyl sulfate was added, followed by heating the reaction mixture at 60 ° for 2 hours. Then the reaction mixture is evaporated in vacuo, the residue is taken up in water and ether and the ether phase is washed with water until neutral, dried and evaporated. The oil obtained is filtered through 100 g of silibagel in chloroform. To give a colorless oil of 1,6-anhydro-3,5-di-O-benzyl-2-O-methyl hyl- ^l / 3-D-glucofuranose of [a?] D ²⁰ = -3 ° (chloroform). Example 8

A solution of 7-gl, 6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose, 9.65 g (10 ml) of methyl isocyanate and 0.5 ml of triethylamine in 110 ml of benzene is allowed to stand for 15 hours at about 25 °, then evaporated to dryness and the scab obtained dried at 1 Pa. A viscous, colorless syrup of 1,6-anhydro-3,5-di-O-benzyl-2- (N-methylcarbamoyl) -1,5-D-glucofuranose was obtained with [ _.alpha. ] _D @ ²⁰ = -16.9 DEG (chloroform).

Example 9

A solution of 7 gl, 6-anhydro-3,5-di-O-benzyl-glucofuranose _and SD, 8.15 g (7.45 ml) of phenyl isocyanate and 10 drops of triethylamine in 100 ml of benzene was heated for 4 hours under reflux cooler. After evaporating to dryness, the syrupy residue is chromatographed on 350 g of silica gel in a 50: 1 mixture of chloroform and acetone to give a viscous syrup of 1,6-anhydro-3,5-di-O- (N-phenylbarbamoyl) -sulfonate. [.Alpha.] _D -D-glucofuranose [ _.alpha. ] _D @ ²⁰ = -27.1 DEG (chloroform).

Example 10

To a solution of 5-gl, 6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose in 30 ml of pyridine was added a solution of 2.3 g (1.91 ml) of benzoyl chloride in 10 ml of chloroform and the reaction mixture. is left for 15 hours at 25 °. After addition of water, the reaction mixture is concentrated in vacuo to a syrup which is dissolved in ether and the ether phase is shaken with 1 N hydrochloric acid solution, sodium bicarbonate solution and water, then dried and evaporated. Crystals of 1,6-anhydro-2-O-benzoyl-3,5-di-O-benzyl- (β-D-glucofuranose) are recrystallized from a mixture of ether and petroleum ether, m.p. [ _.alpha. ] _{D @} ²⁰ = + 7.3 DEG (chloroform).

Example 11

To a cooled solution of 5 g of 1,6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose in 50 ml of pyridine was added a solution of 6.2 g of p-tosyl chloride in 20 ml of chloroform. After standing at 60 ° for 5 hours and at 25 ° for 15 hours, the reaction mixture is diluted with water, evaporated in vacuo to a syrup which is taken up in ether, and the solution is shaken using 1 N hydrochloric acid, 5% sodium bicarbonate solution and water. After drying and evaporation of the ether phase, crystals of 1,6-anhydro-3,5-di-O-benzoyl-2-O- (p-toluenesulfonyl) - (3-D-glucofuranose) are obtained, which are recrystallized from methanol. Mp 92-92.5 °, [α] _D ²⁰ = -40.6 ° (chloroform).

Example 12

To a cooled solution of 5 g of 1,6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose in 50 ml of pyridine was added a solution of 3.68 g (2.44 ml) of mesyl chloride in 20 ml of chloroform. The reaction mixture was allowed to stand for 15 hours at 25 °. Working up as in Example 11 gave 1,6-anhydro-3,5-di-O-benzyl-2-O-imethylisulfonyl- [beta] -D-glucofuranose crystals having a melting point of 142-144 DEG C. after recrystallization from methanol. [.Alpha.] _D @ ²⁰ = -22.4 DEG (chloroform).

Example 13

A solution of 10 g of 2-O-acetyl-1,6-anhydro-5-O-benzyl-3-O-methyl-.beta.-D-glucofuranose in 200 ml of dry methanol is stirred with 0.3 g of potassium carbonate with exclusion of moisture. 16 'hours at about 25 ^c . The methanol was then distilled off under reduced pressure, and the residue was taken up in ether. The ether solution was washed with water until neutral, dried over anhydrous sodium sulfate, and evaporated after filtration. The residue was purified by silica gel column chromatography eluting with methylene chloride / methanol (15: 1). The thus obtained 1,6-anhydro-5-O-benzyl-3-O-methyl- (3-D-glucofurancsa), which is degassed under high vacuum, is obtained in the form of a yellow oil of Rf = 0.45 (thin layer chromatography on silica gel) in the system methylene chloride-methanol 15: 1 [ta] _D ²⁰ = -8 ° ± 1 ° (chloroform, c = 1.234).

Example 14

A solution of 25 g of 2-O-acetyl-1,6-anhydro-5-O-benzyl-3-On-propyl-5-D-glucofuranose in 500 ml of methanol is treated with 0.8 g of potassium carbonate as described above. in Example 13, and the like, the reaction mixture and the product are worked up and purified. Thus, a method of obtaining a high vacuum degassed l, 6-anhydro-5-O-benzyl-3-one-propyl-.beta.-D-glycofuranose is obtained with dolstane as yellowish oil _Rf = 0.45 (when chromatographed on a thin layer chromatography) eluting with methylene chloride: methanol = 15: 1 _[a] ²⁰ = -4 ° ± 1 ° (chloroform, c = 0.705).

Example 15

A solution of 28 g of 2-O-acephyl-1,6-anhydro-5-op-chlorobehzyl-3-on-propyl- [beta] -D-glucofuranose in 560 ml of methanol is treated analogously to Example 14. , 9 g of potassium carbonate. Similarly, the reaction mixture is worked up. The residue was purified by silica gel column chromatography, eluting with a 85:15 mixture of methylene chloride and ethyl acetate. The 1,6-anhydro-5-op-chlorobenzyl-3-On-propyl- [beta] -D-glucofuranose thus obtained and degassed in a high vacuum is obtained as a clear, yellowish oil having an Rf = 0.2 (chromatographic ha thin) JV-layer chromatography system methylonchlorid and ethyl acetate ratio of 86:15 and even [a] _D ²⁰ = -10 ° ± 1 ° (chloroform, c = 1.026).

Example 1 6

A solution of 18.1 g of 5, 5-anhydro-2-O-benzyl-3-on-propyl-5S-D-xylofuranose in 180 ml of ethanol is hydrogenated in the presence of 1.5 g of 5% palladium on carbon catalyst as catalyst. normal pressure and room temperature for 12 hours. Hydrogen consumption is 1.58 liters (103%). The catalyst is filtered off, washed with ethanol, and the filtrate is evaporated to dryness in a water pump vacuum. The 1,5-anhydro-3-O-n-propyl- (SD-xylofuranose) obtained is distilled under high vacuum from a bead flask, boiling at 105-130 ° (bath temperature) at 27 Pa, optical rotation [α] ²⁰ = -170 ± 1 ° (c = 1.225, chloroform), and R _? = 0.1 when thin-layer chromatography on silica gel in ether / petroleum ether 1: 2.

Example 17

A mixture of 16 g, 6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose in 60 ml of pyridine and 14 g of acetylsalicylic acid chloride in 40 ml of chloroform is allowed to react for 2 hours at 50 °. After addition of ice water, it is taken up in chloroform and the chloroform layer is shaken successively with 2 N hydrochloric acid solution, 5% sodium bicarbonate solution and water. After drying over anhydrous sodium sulfate and further conventional work-up, 1,6-anhydro-2-O-salicyloyl-3,5-di-O-benzyl-5-D-glucofuranose is obtained as an oil which is chromatographed on silica gel using cyclohexane. and ethyl acetate 7: 3. [ _.alpha. ] _{D @} ²⁰ = + 7.0 DEG (chloroform, c = 1).

(·

Example 18

A solution of 5-gl, 6-anhydro-2-O-salicyloyl-3,5-di-O-benzyl-β-D-glucofuranose in 30 ml of pyridine was acetylated at 50 ° with 10 ml of acetic anhydride. After 15 hours, methanol is added at about 25 °, the solution is distilled off, and the residue is taken up in chloroform. The chloroform phase is shaken with 1 N hydrochloric acid solution, sodium bicarbonate solution and water. A syrupy 1,6-anhydro-2-O-acetylsal is obtained ^; eyloyl-3,5-di-O-benzyl-β-D-glucofanose, which crystallizes from ether. The melting point is 87-88 ° and [α] _D ²⁰ = -5.2 ° (chloroform, c = 1.55).

Example 19

To a solution of 8 g, 6-anhydro-3,5-di-O-benzyl-5-D-glucofuranose in 40 ml of absolute dimethylsulfoxide was added 1.23 g of sodium hydride dispersion and after completion of hydrogen evolution was added solution 4. 5 g of 2-diethylaminoethyl chloride in 25 ml of dimethyl sulfoxide. After 2 hours, the reaction mixture is evaporated at 60 °, the residue is taken up in ether and the ether phase is washed with water and brine. After drying and evaporation, 1,6-anhydrb-2-O- (2-diethylamino-ethyl) -3,5-di-O-benzyl-β-D-glucofuranone was obtained as an oil which was chromatographed on silica gel using 8: 2 chloroform: acetone; [α] _D ²⁰ = + 2.6 ° (chloroform, c = 3.2).

Treatment with a solution of hydrogen chloride in ethanol gives the corresponding hydrochloride, m.p. 113-114; [Α] ²⁰ D = 0 ° (chloroform, c = 1.05).

Example 20

A solution of 5 g of 1,6-arihydro-2-O-benzoyl-3,5-di-O-benzyl-5-D-glucofuranose in methanol is hydrogenated at about 25 ° to 5% palladium on carbon. The consumption of 1 molar equivalent of hydrogen is complete per hour, after which the hydrogenation is discontinued. 1, 6-anhydro-2-O-benzoyl-3-O-benzyl-β-D-glucofuranose is obtained as crystals of m.p.

Example 21

Solution 26.0 g 2,5-di-O-acetylsalicyloyl-3-O-benzyl-1,6-anhydro- [beta] -D-glucof ^; of uranol in 860 ml of a 1N solution of hydrogen chloride in absolute ethanol is allowed to stand at room temperature for 20 hours, after which the solvent 1 of hydrogen chloride is distilled off under reduced pressure. The residue is taken up in ether and the solution is washed with saturated sodium bicarbonate solution and water, then dried over sodium sulfate, filtered and the solvent is evaporated. The residue was purified by column chromatography on 1200 g of silica gel using an ether / petroleum ether (1: 1) mixture to give 2,5-di-O-salcyloxy-3-O-benzyl-1,6-anhydro- β-D-glucofuranois as white crystals, mp 102-103.5 ° with optical rotation [α] _D ²⁰ = = -3 ° ± 1 ° (chloroform, c = 0.818).

Example 22

21.5 g of 2-O-acetyl-1,6-anhydro-3,5-di-O-benzyl-4'-allofuranose are stirred for 15 hours with a solution of 0.8 g of potassium carbonate in 500 ml of methanol at a temperature of about 20 °. The reaction mixture was evaporated, the residue was taken up in ether and the ethereal solution was washed with water. After drying, filtration and evaporation of the ether phase, a syrup is obtained which is purified by bromo-chromatography on a silica gel column eluting with a 3: 1 mixture of methylene chloride and ethyl acetate. The l, 6-anhydro-3 ^and 5-di-0-benzyl- / SD-allofuran'0sa precipitated as white crystals, mp 60-62 °. _Rf = 0.42 (thin layer chromatograifle siilikagelu) eluting miethylénchloríd and ethyl acetate 3: 1st [ ^α ] _D = + 17 ° + 1 ° (chloroform, c = 0.979).

Example 23

Analogously to Example 10, 1,6-anhydro-3,5-di-O-benzyl-β-D-allofuranosyl and benzovl chloride 1,6-anhydro-2-O-benzoyl-3 were obtained. , _{5-di-0-benzyl-3-one} D-alilofuranosa. Melting point: 128.5 to 129 °.

Example la d 2 4

Analogously to Example 9, 1,6-anhydro-3,5-di-O-benzyl-, 1,6-anhydro-3,5-di-O-benzyl-p-D-allofuranose and phenyl isocyanate were obtained. 2-O- (N-phenylcarbamoyl) -S-D-allofuranose, m.p. 126-128 °.

Example 25

To a solution of 3-gl, 6-anhydro-3-O-benzyl- (SD-glucofuranose in 20 ml of pyridine) was added 3 ml of benzoyl chloride and the reaction mixture was allowed to stand at 50 ° C for 2 days. Most of the pyridine was evaporated in vacuo and the residue was stirred with ice to give 1,6-anhydro-2,5-di-O-benzoyl-3-O-benzyl-5-D-glucofuranosulfate as crystals. M.p. 136 DEG-137 DEG C. [ _.alpha .] _D @ ²⁰ = -9.1 DEG (chloroform, c = 1.04).

Example 26

Similar to Example 10, 1,6-anhydro-3,5-di-O- is obtained from 1,6-anhydro-3,5-di-O-benzyl- [beta] -D-allofuranois and α-naphthoic acid chloride. Bisyl-, 2-O- (β-naphthoyl) - β-D-allofuranose, m.p. 113-114 °.

Example 27

In analogy to Example 10, 1,6-anhydro-3,5- is obtained from 1,6-a, thihydro-3,5-di-O-benzyl- [beta] -D-glucofuranose and α-naphthoic acid chloride. di-O-benzyl-2-O- (α-naphthoyl) - β-D-glucofuranose, oil, [α] _D ²⁰ = -12.4 ° ± 0.3 ° (c = 0.74, chloroform) _Rf = 0.66 (chloroform, ethyl acetate = 7: 3), silica gel plates).

Example 28

To a solution of 12.6 g of 3-O-benzyl-1,6-anhydro- [beta] -D-glucofuranose in 100 ml of methyl chloride and 15 ml of pyridine was added dropwise a solution of 21.8 g of lacetylsalicylic chloride with stirring at 40 DEG over 15 hours. in 100 ml methylene chloride. After addition of 20 ml of water, both methylene chloride and pyridine are distilled off under reduced pressure. The residue is taken up in diethyl ether and the solution is washed with ice-cold 2 N hydrochloric acid solution, saturated sodium bicarbonate solution and water. After drying, filtration and evaporation, the residue obtained is chromatographed on a column of 1200 g of silica gel, eluting with a 1: 1 mixture of ether and petroleum ether. Are thus obtained 2,5-di-0-acetylsalicyloyl-3-O-benzyl-lb-anhydro-ss-D-glukofuranoisa that děsacetyiluje as described in Example 21. The product is an oil, R _f = 0.65 (methylene chloride, ethyl acetate = 85:15, finished silica gel plates [Merck]).

Example 29

Capsules containing 0,1 g of the active substance may be prepared as follows (for 10 000 capsules):

Ingredients:

1,6-anhydro-3,5-di-O-benzyl-β-D-glucofuranose 1000 g absolute ethanol 100 g

1 H-Anhydro-5 S-di-O-benzyl-4-D-glucofuranoe Mix with ethanol and fill the mixture with a suitable capsule device of soft gelatin capsule.

Claims (9)

SUBJECT A process for the preparation of novel anhydrofuranose derivatives of the general formula I CH-A-O-CH CVORγ-CHOR _of (I) wherein R2 is hydrogen, (C1-C4) -alkyl, (C1-C4) -alkyl, (C1-C4) alkenyl, (C1-C4) -phenylalkyl or (C1-C4) alkanoyl; carbon atoms, optionally hydroxyl or C 1 -C 4 alkanoyloxy or halogen substituted benzoyl net naphthoyl, C 1 -C 4 alkylsulfonyl, toluenesulfonyl, pyridylcarbamoyl, R 3 represents hydrogen, alkyl or alkenyl of up to 4 carbon atoms, optionally hydroxyl or; (C 1 -C 4) alkanoyloxy or halogen-substituted benzoyl or (C 1 -C 4) alkanoyloxy or optionally halogen-substituted phenyl or C 1 -C 2 -alkyl and the group "A-O" represents a radical of the general formula of formula —OHOR5 —CH2 —O— or —CH (CH2OR6) —O— in which R 5 and R 6, respectively, have one of the meanings given for R 3, or wherein -CH 2 ORe represents hydrogen, or wherein two of the radicals R 2, R 3 and R 5 and R 6 together represent an alkylidene or phenylailkylidene group having 1 to 4 carbon atoms in the alkylidene moiety, one of the radicals R 2, R 3 and R 5 and R 6, respectively, have a meaning other than hydrogen, and wherein in the compounds with the group -CHOR 5 -CH 2 -O- in the meaning of the group -A-O- one of the radicals * R 2, R 3 and R 5 are other than methyloYANESIS when the other two of these are methyl, and wherein in the compounds with the group -OHOR 5 -CH 2 -O- in the meaning of the group -A-O-, one of the radicals is one, R2, R3 and R5 in the meaning of the group —A — ιπιά are other than acetyl, provided that the other two of these residues denote an acetyl group, and in the compounds with the group - CHpCHaORea - O— in the sense of the group —A — O— one of the residues R2, R5 and R6 are other than benzyl when the other two are henzyl. or a salt thereof, characterized in that the compound of formula V is treated with an acid or a base I | ^Λ CH - A - Q - CH \ / CHQR ^ - _c $, _O p _of (V) where A, R 2 and R 3 have the meanings given above and one of the general symbols X 1 and X 2 are each a reactively esterified or etherified hydroxyl group and, if desired, the substituents are introduced, varied and / or cleaved into the compounds obtained, and / or the racemate mixtures obtained are separated into pure racemates and / or obtained The racemates are resolved into optical antipodes and / or the salts obtained are converted into free compounds or other salts, or the obtained free compounds are converted into their salts. 2. The process according to claim 1, wherein the starting material is a compound of formula (V) wherein X1 or X2 as the reactive etherified hydroxyl group is a benzyloxy group. 3. The process according to claim 1, wherein the compound of formula V is treated with a Lewis acid, a strong inorganic acid or an inorganic or organic base. 4. A process according to any one of claims 1 to 3, wherein the starting compound of formula V is used, wherein the group -A-O- is the radical -OHORs -CH2-O- and R2, R3 and R5 are not independently from each other. le represents hydrogen, alkyl, (C1 -C4) -alkyl, benzyl, (C1 -C4) -alkoxybenzyl, halobenzyl, alkenoyl (C1 -C4), benzoyl, halobenzoyl, hydroxybenzoyl, alkanoyloxybenzoyl having 1 to 4 carbon atoms in the alkanoyl moiety or pyridylcarbomyl, or two of R2, R3 and R5 being C1-C4alkylidene or benzylidene, respectively, one of R2, R3 and R 5 is other than hydrogen when the other two of these radicals are hydrogen, and one of R 2, R 3, and R 5 is other than methyl, when the other two the radicals are methyl and one of the radicals R2, R3 and R5 is other than acetyl, if the other two of these radicals are acetyl and X1 and X2- are as defined above. 5. A process according to any one of claims 1 to 3, wherein the starting compound of formula V is used, wherein -A-O- is -OHOR5-CH2-O-, R2 is hydrogen, C1-C6 alkyl. 3 carbon atoms, dialkylaminoalkyl together with up to 7 carbon atoms, benzyl, alkanoyl of 2 to 4 carbon atoms, benzoyl, o-hydroxybenzoyl, o-alkanoyloxybenzoyl of 2 to 4 carbon atoms in the o-alkamoyloxy moiety, naphthoyl, alkylcarbamoyl of up to 4 carbon atoms, phenylcarbamoyl, alkylsulphonyl of 1 to 3 carbon atoms, toluylsulphonyl or pyridylcarbonyl, and R2 and R5 are each independently hydrogen, alkyl of 1 to 3 carbon atoms; y is selected from the group consisting of carbon, benzyl, chloro, benzyl or benzoyl, wherein one of R2, R3 and R5 is other than hydrogen when the other two are hydrogen, and wherein one of e, R2, R3 and R5 are other than methyl when the other two are methyl, and one of R2, R3 and R5 is other than acetyl when the other two are acetyl, and X 1 and X 2 are as defined above. 6. A process according to any one of claims 1 to 3, wherein the starting compound of formula V is used, wherein the group -A-O- is the radical -CHOR5 -CHa-O-, R2 is an alkanoyl group of 2 to 4 and carbon atoms, benzoyl, o-hydroxybenzoyl, o-alkanoyloxybenzoyl of 2 to 4 carbon atoms in the O-alkanoyloxy moiety, naphthoyl or pyridylcarboinyl, R 3 and R 5 are each independently hydrogen, 2 or 3 carbon atoms, benzyl, chlorobenzyl, benzoyl or o-hydroxybenzoyl and X1 and X2 are as defined above. 7. A process according to any one of claims 1 to 3, wherein the starting compound of formula V is used, wherein the group -A-O- is the radical -CHOR5 -OH2-O-, R2 is hydrogen and R3 and Rs are mutually are independently C1 -C3 alkyl, allyl, rmethallyl, benzyl or chlorobenzyl and X1 and X2 are as defined above. 8. A process according to any one of claims 1 to 3, wherein the compound of formula (V) is used, wherein -A-O- is a radical -CHOR5-CH2-O-, R2 is hydrogen; C 2 -C 4, benzoyl, o-hydroxybenzoyl, o -acetoxybemzoyl, naphthoyl or pyridylcarbonyl, and R 3 and R 5 are each independently C 1 -C 3 alkyl, benzyl, chlorobenzyl, benzoyl, o- hydroxybenzoyl, o-acetoxybenzoyl or naphthoyl, X 1 and X 2 are as defined above. 9. A process according to any one of Claims 1 to 3, wherein the starting compound of formula V is used, wherein the group —A — O — means the radical —CHOR5 — CH2 ———————————————————————————————————————————— and X21 are as defined above.