DE2508826A1 - NEW 1,3-BENZODIOXANE PROSTANIC ACID DERIVATIVES AND THE PROCESS FOR THEIR PRODUCTION - Google Patents

Description

It is generally known that the diverse effects of prostaglandins both in the mammalian organism and in vitro are only of short duration, since they are quickly converted into pharmacologically inactive metabolic products. A largely inactive metabolite is formed by oxidation of the allylic hydroxyl function on carbon atom 15 by 15-hydroxy-prostaglandin dehydrogenases.

It was therefore desirable to develop prostaglandin analogs with a spectrum of activity comparable to that of natural prostaglandins and to make structural changes that increase the duration and selectivity of the effectiveness.

It has now been found that 1,3-benzodioxane prostaglandins surprisingly have a longer duration of action, greater selectivity and better effectiveness than the natural prostaglandins.

The invention relates to 1,3-benzodioxane-prostanoic acid derivatives of the general formula I and their antipodes and racemates

wherein

R deep 1 is a hydroxyl group, a straight or branched alkoxy group with 1 - 10 carbon atoms, a methylsulfamide group, a substituted or unsubstituted aryloxy group, an O-CH deep 2-UV group, where U is a direct bond, a carbonyl or carbonyloxy group and V denotes a phenyl ring substituted by one or more phenyl groups, alkoxy groups with 1 - 2 carbon atoms or halogen atoms, preferably bromine atoms,

A denotes a CH deep2-CH deep2- or a trans -CH = CH group,

B denotes a -CH deep2-CH deep 2- or a cis or trans-CH = CH group,

Z represents a hydroxymethylene or a carbonyl group,

XY for or when Z represents a hydroxymethylene group or represents or -CH = CH- if Z is a carbonyl group,

R deep2 denotes a hydrogen atom or an alkyl group with 1-5 C atoms,

R deep 3 and R deep 4 are the same or different and represent H, F, Cl, Br, J, CF deep 3, CH deep 3 or alkoxy groups with 1 - 2 carbon atoms and if R deep 1 represents a hydroxyl group, the salts with physiologically acceptable bases

Examples of substituted or unsubstituted aryloxy groups R deep 1 are: phenoxy, 1-naphthoxy and 2-naphthoxy, each of which can be substituted by 1 - 3 halogen atoms, 1 phenyl group, 1 - 3 alkyl groups each with 1 - 4 carbon atoms, 1 chloromethyl, fluoromethyl, trifluoromethyl, carboxyl or hydroxyl group.

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Possible alkyl groups R deep2 are those with 1-5 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and pentyl groups.

All inorganic and organic bases are suitable for salt formation, as are known to the person skilled in the art for the formation of physiologically compatible salts. Examples include alkali hydroxides such as sodium or potassium hydroxide, alkaline earth hydroxides such as calcium hydroxide, ammonia, amines such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, morpholine, tris (hydroxymethyl) methylamine, etc.

The invention also relates to a process for the preparation of the new 1,3-benzodioxanprostanoic acids, characterized in that a lactol of the general formula II where R deep2, R deep3, R deep4 and A have the meaning given above and R deep5 and R deep6 denote a hydrogen atom or a hydroxyl protecting group with a Wittig reagent of the general formula III

Ph deep3 P = CH- (CH deep2) deep3-COR deep1,

where Ph is a phenyl group and R deep 1 has the meaning given above, after which, if desired, after oxidation of the 9-hydroxy group, any hydroxyl protective groups present are split off again and then depending on the ultimately desired meaning of R deep 1, R deep 2, R deep 3, R deep 4, R deep 5, R deep 6, A, B, XY and Z in the end product, optionally in any order, esterified a free 1-carboxy group or saponified an esterified 1-carboxy group and / or reduced a 9-keto group and / or a 5,6 double bond hydrogenated and / or a 13,14 and 5,6 double bond hydrogenated and / or a 9-keto compound dehydrated with elimination of the 11-hydroxy group and / or a 9-hydroxy group after intermediate protection of the 11 - and 15-hydroxyl group is oxidized and / or an 11-hydroxyl group is oxidized after intermediate protection of the 9- and 15-hydroxyl group and optionally a 1-carboxy compound with a base is converted into a physiologically acceptable salt transferred and optionally separates the racemates.

The reaction of the lactols II with the Wittig reagent of the general formula III, which is prepared in the usual way in dimethyl sulfoxide from the corresponding phosphonium bromide with methanesulfinylmethyl sodium or potassium tert-butoxide, is carried out at temperatures of 0 ° C.-100 ° C., preferably at 20 ° C - 80 ° C, in an aprotic solvent, preferably dimethyl sulfoxide or

Dimethylformamide. The Wittig reagent can also be released from 4-R deep-1-CO-triphenylbutylphosphonium bromide with potassium tert-butoxide during the reaction.

The oxidation of the 9-hydroxy group to the ketone, which can take place before the hydroxy protective groups are split off, is carried out with the usual oxidizing agents, for example with Jones reagent (J. Chem. Soc. 1953, 2555). An excess of the oxidizing agent in a suitable diluent, such as acetone, is used at temperatures between 0.degree. C. and -50.degree. C., preferably at -20.degree. The reaction is generally complete after 5 to 30 minutes.

The 9-hydroxy group is preferably oxidized after intermediate protection of the 11- and 15-hydroxy groups, for example by silylation (Chem. Comm. (1972), 1120). Other suitable oxidizing agents are silver carbonate on "Celite" or mixtures of chromium trioxide and pyridine (Tetrahedron Letters 1968, 3363).

The oxidation of the 11-hydroxyl group is carried out with the usual oxidizing agents, for example with Jones reagent or Collins reagent after intermediate protection of the 9- and 15-hydroxyl groups. One works at temperatures between -40 ° C and + 20 ° C, preferably at -20 ° C.

The radicals known to those skilled in the art are introduced as hydroxy protective groups, preferably cyclic small alpha, small beta-unsaturated ethers, such as dihydropyran, dihydrofuran and small alpha-ethoxyethylene and acyl radicals, such as aromatic and aliphatic organic acid groups, but preferably benzoyl - and acetyl radical.

The elimination of the hydroxy protective groups such as THP, THF to the compounds of general formula I is carried out by known methods in an aqueous solution of an organic acid, such as acetic acid, propionic acid, etc., or in an aqueous solution of an inorganic acid, such as hydrochloric acid, carried out. To improve the solubility, a water-miscible inert organic solvent is expediently added. Suitable organic solvents are, for example, alcohols such as methanol and ethanol, and ethers such as dimethoxyethane, dioxane and tetrahydrofuran. Tetrahydrofuran is preferred. The hydrolysis is preferably carried out at temperatures between 20 ° C and 80 ° C. In the case of compounds of prostaglandin E type, the hydrolysis is carried out below 45 ° C in order to avoid the formation of prostaglandin A compounds as by-products.

The acyl groups are split off with alkali metal carbonates, for example potassium carbonate in methanol at 0 to 50.degree. C., preferably at 25.degree.

The reduction of the 9-oxo group to a mixture of the epimeric 9-small alpha and 9-small beta alcohols is carried out in the customary manner, preferably in an organic solvent with sodium borohydride or zinc borohydride. If zinc borohydride is used, possible solvents are, for example, dimethoxyethane, diethyl ether, dioxane, benzene, isopropyl ether. When using sodium borohydride, methanol, ethanol, isopropanol, n-propanol, for example, come into consideration as solvents. The resulting mixture of epimers is separated, for example, in the customary manner by column or layer chromatography and / or fractional crystallization.

The dehydration of the 9-oxo compound, in which the 11-hydroxy group and a hydrogen atom are split off from the 10-position to give a postaglandin A derivative, can be carried out under conditions that are generally known to the person skilled in the art. In general, the dehydration takes place in a solution of an organic acid, such as acetic acid, or an inorganic acid, such as hydrochloric acid, at temperatures between 20.degree. C. and 80.degree. The reaction has ended after about 2 to 17 hours.

The hydrogenation of the 13,14- and / or 5,6-double bond is carried out in a manner known per se in a hydrogen atmosphere in the presence of a noble metal catalyst. A suitable catalyst is, for example, 10% palladium on carbon. If hydrogenation is carried out at room temperature, both the 5,6 and the 13,14 double bond can be saturated. At low temperatures, preferably at -80 ° C. to -10 ° C., the cis-5,6 double bond can be hydrogenated before the trans-13,14 double bond. A selective reduction of the cis-5,6 double bond with the simultaneous presence of a trans-13,14 double bond is also brought about with the catalyst nickel boride or tris (triphenylphosphine) rhodium (I) chloride.

To prepare the esters of the general formula I in which R 1 represents an alkoxy group with 1-10 carbon atoms, the 1-carboxy compounds are reacted with diazo hydrocarbons in a manner known per se. Esterification with diazo hydrocarbons is carried out, for example, by mixing a solution of the diazo hydrocarbon in an inert solvent, preferably in diethyl ether, with the 1-carboxy compound in the same or in a different inert solvent, such as methylene chloride. After the reaction has ended in 1 to 30 minutes, the solvent is removed and the ester is purified in the usual way.

Diazoalkanes are either known or can be prepared by known methods [Org. Reactions Vol. 8, pp. 389-394 (1954)].

To introduce the ester group O-CH deep2-U-V- for R deep1, the 1-carboxy compound of the general formula I is mixed with a halogen compound of the general formula

Hal-CH deep2-U-V,

where Hal is a halogen atom, preferably bromine, U is a direct bond, a carbonyl or carbonyloxy group and V is a phenyl ring substituted by one or more phenyl groups, alkoxy groups having 1 - 2 carbon atoms or halogen atoms, preferably bromine atoms, in the presence of a hydrogen halide splitting agent implemented.

Silver oxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or amines, such as trimethylamine, triethylamine, tributylamine, trioctylamine and pyridine, are used, for example, as agents which split off hydrogen halide. The reaction with the halogen compound is carried out in an inert solvent, preferably in acetone, acetonitrile, dimethylacetamide, dimethylformamide or dimethyl sulfoxide at temperatures from -80 ° C. to + 100 ° C., preferably at room temperature.

To prepare the esters of general formula I, in which R 1 represents a substituted or unsubstituted aryloxy group, the 1-carboxy compounds are reacted with the corresponding arylhydroxy compounds with dicyclohexylcarbodiimide in the presence of a suitable base, for example pyridine or triethylamine, in an inert solvent. Suitable solvents are methylene chloride, ethylene chloride, chloroform, ethyl acetate, tetrahydrofuran, preferably chloroform. The reaction is carried out at temperatures between -30 ° C and + 50 ° C, preferably at 10 ° C.

The saponification of the prostaglandin esters takes place according to the methods known to the person skilled in the art, for example with potassium hydroxide in methanol.

The prostaglandin derivatives of the general formula I with R deep 1 meaning a hydroxyl group can be converted into salts with equivalent amounts of the corresponding inorganic bases with neutralization. For example, when the corresponding PG acids are dissolved in water which contains the stoichiometric amount of the base, the solid inorganic salt is obtained after evaporating the water or after adding a water-miscible solvent, for example alcohol or acetone.

To prepare an amine salt, the PG acid is dissolved in a suitable solvent, for example ethanol, acetone, diethyl ether or benzene, and at least the stoichiometric amount of the amine is added to this solution. The salt is usually obtained in solid form.

The lactols of the general formula II used as starting compounds can be prepared by converting 2-hydroxymethylphenols (saligenins) with dihalocarboxylic acids to give 1,3-benzodioxane-2-carboxylic acids of the general formula IV where R deep2, R deep3 and R deep4 have the meaning given above. The 1,3-benzodioxane-2-carboxylic acid obtained in this way is present because of the asymmetric carbon atom in position 2 as a racemate which can be separated into the optical antipodes by salt formation with optically active bases. The subsequent esterification can be carried out with the racemate or with the enantiomer. The 1,3-benzodioxane-2-carboxylic acid ester obtained in this way is reacted with triphenylphosphine methylene or a methylphosphonic acid dialkyl ester and then becomes known per se

A ketone of the general formula V is represented by a Wittig or Wittig-Horner reaction with an aldehyde (preferably in the form of the corresponding antipode) where R deep2, R deep3, R deep4 and R deep5 have the meaning given above. Any C deep 16 diastereomer mixture formed can be separated by customary methods.

In the presence of noble metal salt catalysts, the ketone of the general formula V can be hydrogenated in an inert solvent, if desired in the 13,14-position (PG numbering).

The subsequent reduction to the small alpha and small beta-C deep-15 alcohols is carried out with sodium borohydride or zinc borohydride. The mixture of epimers can be separated according to the conventionally known methods. After the introduction of hydroxy protective groups, such as, for example, dihydropyran, in position 15 and optionally in position 11 (PG numbering) the lactone is reduced with diisobutylaluminum hydride or lithium tri-tert-butoxyaluminum hydride to the desired lactol of the general formula II.

The reduction to the lactol of the general formula II can also be carried out without protecting groups according to a simplified Corey synthesis according to German Offenlegungsschrift P 23 28 131 using diisobutylaluminum hydride or lithium tri-tert.-butoxyaluminum hydride.

To introduce the hydroxy protecting groups, the 11,15-diol (PG numbering) is reacted with, for example, dihydropyran in methylene chloride or chloroform using an acidic condensing agent such as p-toluenesulfonic acid. The dihydropyran is used in excess, preferably in 4 to 10 times the theoretical requirement. The reaction is usually complete after 15-30 minutes at 0 ° C-30 ° C.

One way of representing the starting compounds acetylated in the 11-position is that the lactol etherified in the 15-position (PG numbering) is reacted with acetic anhydride in pyridine. After the lactol hydroxyl group has been released, a lactol of the general formula II is obtained.

The new prostanoic acid derivatives of the general formula I are valuable pharmaceuticals because, with a similar spectrum of activity, they have a much stronger and, above all, much longer action than the corresponding natural prostaglandins.

The new prostaglandin analogs of the E, D and F types have a very strong luteolytic effect, i.e. to trigger luteolysis, significantly lower doses are required than for the corresponding natural prostaglandins.

To induce abortions, significantly smaller amounts of the new prostaglandin analogues are required compared to the natural prostaglandins.

When the isotonic uterine contraction is recorded on the anesthetized rat and on the isolated rat uterus, it is found that the substances according to the invention are significantly more effective and their effects last longer than with the natural prostaglandins.

The new prostanoic acid derivatives are suitable for inducing menstruation or interrupting pregnancy after a single intrauterine application. They are also suitable for synchronizing the sexual cycle in female mammals such as monkeys, cattle, pigs, etc.

The good dissociation of the effects of the substances according to the invention is shown in the investigation of other smooth muscle organs, such as, for example, the guinea pig ileum or the isolated rabbit trachea, where significantly less stimulation can be observed than with the natural prostaglandins.

The active ingredients of the PG E series according to the invention show bronchodilatory action in vitro on the isolated rabbit trachea and strongly inhibit gastric acid secretion and have a regulating effect on cardiac arrhythmias. The new compounds of the PG A and PG E series also lower blood pressure and have a diuretic effect.

The active ingredients of the F series according to the invention have a less bronchoconstrictive effect than natural prostaglandin F deep2 deep small alpha, which is of great advantage for their therapeutic use.

For medical use, the active ingredients can be converted into a form suitable for inhalation, for oral or parenteral administration.

Aerosol or spray solutions are expediently prepared for inhalation.

For example, tablets, coated tablets or capsules are suitable for oral administration.

For parenteral administration, sterile, injectable, aqueous or oily solutions are used.

The invention thus also relates to medicaments based on the compounds of the general formula I and customary auxiliaries and carriers.

The active ingredients according to the invention are intended to be used in conjunction with the auxiliaries known and customary in galenicals, for example for the production of preparations for triggering an abortion, for controlling the cycle or for initiating a birth. For this purpose, sterile, aqueous solutions containing 0.01-10 µg / ml of the active compound can be used as an intravenous infusion solution. The acids and salts of the general formula I are particularly suitable for preparing aqueous isotonic solutions. Alcohols such as ethanol and propylene glycol can be added to increase solubility.

example 1

(5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH. R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

a) 1,3-Benzodioxane-2-carboxylic acid methyl ester

A solution of 12.4 g of saligenin in 100 ml of dimethylformamide was added dropwise to a suspension of 9.6 g of 50% sodium hydride in 100 ml of dimethylformamide with ice-water cooling. The reaction mixture was stirred at room temperature overnight. 9 ml of dichloroacetic acid were added to 50 ml of dimethylformamide while cooling with ice. A suspension of 5.3 g of 50% sodium hydride in 150 ml of dimethylformamide was added while cooling with ice. The sodium hydride can also be added without a solvent. This sodium dichloroacetate solution was dripped into the first prepared saligenin disodium solution at room temperature. The reaction mixture was stirred at 60 ° C. for a total of 5 hours with the addition of potassium iodide. During the last 3 hours, the dimethylformamide was distilled off using an oil pump. The semi-solid, brown residue was acidified to pH 3 with concentrated aqueous citric acid solution and extracted with methylene chloride. The organic phase was dried over magnesium sulfate, concentrated on a rotary evaporator and mixed with diazomethane solution at approx. 10 ° C. After stirring for 1 hour at room temperature, the excess diazomethane and the solvent were removed with the water pump. The residue was poured into saturated sodium chloride solution, extracted with methylene chloride, the organic phase was dried with magnesium sulfate, concentrated and purified by column chromatography on silica gel with hexane / 5-10% ethyl acetate. 6 g of 1,3-benzodioxane-2-caronic acid methyl ester, melting point 28-29 ° C., were obtained.

b) [2-Oxo-2- (1,3-benzodioxan-2-yl) ethylidene] triphenyl-phosphorane

40 ml of a 2.52 M butyllithium solution in hexane were added dropwise at room temperature under argon to a suspension of 39 g of triphenylmethylphosphonium bromide in 250 ml of absolute ether and the mixture was stirred for 15 hours, also under argon and at room temperature. A solution of 9.78 g of 1,3-benzodioxane-2-carboxylic acid methyl ester in 100 ml of absolute ether was added dropwise to the yellow Ylene solution, the mixture was stirred for 1 hour at room temperature, the white precipitate was filtered off, dissolved in water and extracted with ether.

The organic phase was combined with the filtrate, washed with water, dried over magnesium sulfate and concentrated to dryness. The residue was purified by column chromatography on silica gel with hexane / 20-100% ethyl acetate and then recrystallized from ethyl acetate. Yield: 12 g, melting point 95-98 ° C.

c) (1S, 5R, 6R, 7R) -6 - [(E) -3-Oxo-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -7-benzoyloxy- 2-oxabicyclo [3.3.0] octan-3-one

7 g of (1S, 5R, 6R, 7R) -6-formyl-7-benzoyloxy-2-oxabicyclo [3,3,0] -octan-3-one [E.J. Corey et al. J. Amer. Chem. Soc. 91, 5675 (1969)] and 11.2 g of [2-oxo-2- (1,3-benzodioxan-2-yl) ethylidene] triphenylphosphorane were stirred for 16 hours in 300 ml of benzene under argon at room temperature. It was then evaporated to dryness in vacuo. The residue was purified by column chromatography on silica gel using hexane / 20-60% ethyl acetate as the mobile phase. 5 g of oil were obtained.

d) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] - 7-benzoyloxy-2-oxabicyclo [3,3,0] octan-3-one

A solution of 2 g of the ketone obtained according to c) in 140 ml of absolute dimethoxyethane was mixed with 140 ml of ethereal zinc borohydride solution (Production: Newer Methods of Preparative Organic Chemistry, Vol. 4, p. 241, Verlag Chemie) added and stirred under argon for 2 hours at room temperature. After dilution with 100 ml of ether, the reaction solution was carefully mixed with water, extracted with saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness in vacuo. The reaction products were separated by column chromatography on silica gel using hexane / 30-60% ethyl acetate as the mobile phase. The first product to be eluted was the small alpha alcohol. Yield: 0.8 g

e) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl ] -5-hydroxy-perhydrocyclopenta [b] -furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = hydrogen atom; the OH group at C-3 'is small in the alpha position.

5.5 ml of a 20% solution of diisobutylaluminum hydride in toluene were added under argon to a solution of 550 mg of the lactone alcohol shown in d) in 20 ml of absolute toluene, and the mixture was stirred at -60 ° for 30 minutes C and terminated the reaction by adding 2 ml of isopropanol dropwise. After adding 20 ml of water, the mixture was stirred for 15 minutes at 0 ° C., extracted with ethyl acetate and / or methylene chloride, shaken with saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness in vacuo. 520 mg of crude product of the above lactol were obtained, which was used in the next stage without further purification. f) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

To a solution of 3.46 g of 4-carboxybutyltriphenylphosphonium bromide in 10 ml of absolute dimethyl sulfoxide (DMSO) were added 14.98 ml of a solution of methanesulfinylmethyl sodium in absolute DMSO (preparation: 2 g of 50% sodium hydride suspension were dissolved in 40 ml of absolute DMSO at 70 ° C ) and stirred for 30 minutes at room temperature. This red-brown colored solution was added dropwise with water cooling to a solution of 520 mg of the lactol obtained according to e) in 5 ml of absolute DMSO. The reaction mixture was then stirred for 2 hours at 50 ° C. under argon, then most of the DMSO was distilled off at the oil pump (bath temperature 40-50 ° C.), 50 ml of ice water were added to the residue and extracted three times with ether. This ether extract was discarded. The aqueous phase was acidified to pH deep 4 with 10% citric acid solution, extracted four times with an ether / hexane mixture (1: 1) and three times with methylene chloride. The organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate and

Concentrated to dryness. The residue was purified by chromatography on silica gel using methylene chloride / 1-10% ethanol as the mobile phase. Yield: 310 mg

g) The prostaglandic acid obtained according to f) was dissolved in methylene chloride and esterified with an ethereal diazomethane solution. The evaporation residue was chromatographed on silica gel using methylene chloride / 4% isopropanol as the mobile phase. The methyl prostaglandin carboxylate listed as Example 1 was obtained. Yield: 288 mg [small alpha] high 23 deep D = + 0.8 ° (c = 0.25; CHCl deep 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 2

(5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = hydrogen atom, the OH group at C-15 is small in beta.

In the reaction of (1S, 5R, 6R, 7R) -6 - [(E) -3-oxo-3 - ({2RS} -1,3-benzodioxan-2-yl) -1, described under Example 1 d) -propenyl] -7-benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one, the small beta alcohol was eluted from the column as the 2nd product:

a) (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3-Hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -7- benzoyloxy-2-oxabicyclo [3,3,0] octan-3-one Yield: 0.5 g

b) (2RS, 3aR, 4R, 5R, 6aS, 3'S) -4 - [(E) -3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] - 5-hydroxy-perhydrocyclopenta [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = H; the OH group at C-3 'is small in beta.

410 mg of the small beta alcohol obtained according to a) were reacted with diisobutylaluminum hydride analogously to the procedure in Example 1 e). 400 mg of crude product were obtained.

c) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, Rlow4 = H; the OH group at C-15 is small in beta.

The 400 mg of lactol obtained in b) were reacted without further purification analogously to the procedure in Example 1 f) with 2.66 g of 4-carboxybutyltriphenylphosphonium bromide and 11.52 ml of the methanesulfinylmethylsodium solution described there. Yield: 220 mg.

d) The prostaglandic acid obtained according to c) was dissolved in methylene chloride and esterified with an ethereal diazomethane solution. The evaporation residue was chromatographed on silica gel using methylene chloride / 4% isopropanol as the mobile phase. The methyl prostaglandin carboxylate listed as Example 2 was obtained. Yield: 198 mg [small alpha] high 23 deep D = -0.8 ° (c = 0.25; CHCl low 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 3

(5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position. a) (1S, 5R, 6R, 7R) -6 - [(E) -3-Oxo-3 - ({2R} -1,3-benzodioxan-2-yl) -1-propenyl] -7-benzoyloxy- 2-oxabicyclo [3.3.0] octan-3-one

The substance was obtained in the form of colorless crystals by benzene / ether crystallization of the oil described under Example 1 c). Melting point: 129-130 ° C; [small alpha] high23 lowD = -147.4 ° (CHCl low3)

b) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-hydroxy-3 - ({2R} *) -1,3-benzodioxan-2-yl) -1-propenyl ] -7-benzoyloxy-2-oxabicyclo [3,3,0] octan-3-one

From 1.5 g of the ketone obtained according to Example 3 a), the small alpha alcohol was obtained as the first product of column chromatography according to Example 1 d) by zinc borohydride reduction. Yield: 0.61 g [small alpha] high 23 low D = -101.3 ° (CHCl low 3)

c) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-hydroxy-3 - ({2R} -1,3-benzodioxan-2-yl) -1-propenyl ] -5-hydroxy-perhydro-cyclo-penta [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = hydrogen atom, the OH group at C-3 'is in a small alpha position.

600 mg of the small alpha alcohol obtained according to b) were reacted with diisobutylaluminum hydride analogously to the procedure in Example 1 e). 450 mg of crude product were obtained.

d) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, R deep4 = hydrogen atom, the OH group at C-15 is in a small alpha position.

The 450 mg of lactol obtained in c) were reacted without further purification analogously to the procedure in Example 1 f) with 3.8 g of 4-carboxybutyltriphenylphosphonium bromide and 16.5 ml of the methanesulfinylmethylsodium solution described there. Yield: 315 mg

e) The prostaglandic acid obtained according to d) was dissolved in methylene chloride and esterified with an ethereal diazomethane solution. The evaporation residue was chromatographed on silica gel using methylene chloride / 1-6% isopropanol as the mobile phase. The methyl prostaglandin carboxylate listed as Example 3 was obtained. Yield: 299 mg [small alpha] high 23 deep D = -21.2 ° (c = 0.4; CHCl low 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 4

(5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = hydrogen atom, the OH group at C-15 is small in beta.

In the zinc borohydride reduction of (1S, 5R, 6R, 7R) -6 - [(E) -3-oxo-3 - ({2R} -1,3-benzodioxan-2-yl) - 1-propenyl] -7-benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one (Example 3a) the small beta alcohol was eluted from the column as the 2nd product:

a) (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3-hydroxy-3 - ({2R} -1,3-benzodioxan-2-yl) -1-propenyl] -7- benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one Yield: 0.41 g [small alpha] high 23 low D = -128 ° (CHCl low 3)

b) (2RS, 3aR, 4R, 5R, 6aS, 3'S) -4 - [(E) -3-hydroxy-3 - ({2R} -1,3-benzodioxan-2-yl) -1-propenyl] - 5-hydroxy-perhydro-cyclo-penta [b] furan-2-ol

General formula II: A = trans, CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = hydrogen atom, the OH group at C-3 'is small in beta.

410 mg of the small beta alcohol obtained according to a) were reacted with diisobutylaluminum hydride analogously to the procedure in Example 1 e). 400 mg of crude product were obtained.

c) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, R deep4 = hydrogen atom, the OH group at C-15 is small in beta.

The 400 mg of lactol obtained in b) were reacted without further purification analogously to the procedure in Example 1 f) with 2.66 g of 4-carboxy-butyltriphenylphosphonium bromide and 11.52 ml of the methanesulfinylmethylsodium solution described there. Yield: 230 mg

d) The prostaglandic acid obtained according to c) was dissolved in methylene chloride and esterified with an ethereal diazomethane solution. The evaporation residue was chromatographed on silica gel using methylene chloride / 1-6% isopropanol as the mobile phase. The methyl prostaglandin carboxylate listed as Example 4 was obtained. Yield: 212 mg [small alpha] high 23 deep D = -46.4 ° (c = 0.25; CHCl low 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 5

(5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

a) (1S, 5R, 6R, 7R) -6 - [(E) -3-oxo-3 - ({2S} -1,3-benzodioxan-2-yl) -1-propenyl] -7-benzoyloxy- 2-oxabicyclo [3.3.0] octan-3-one

The mother liquor obtained according to Example 3 a) was chromatographed by column chromatography on silica gel with hexane / 20-50% ethyl acetate as the mobile phase. [small alpha] high23 lowD = -18.8 ° (CHCl low3)

b) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-hydroxy-3 - ({2S} -1,3-benzodioxan-2-yl) -1-propenyl] - 7-benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one

From 3 g of the ketone obtained according to Example 5 a), the small alpha alcohol was obtained as the first product of a column chromatography repeated several times according to Example 1 d) by zinc borohydride reduction. Yield: 1.1 g c) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-hydroxy-3 - ({2S} -1,3-benzodioxan-2-yl) -1-propenyl ] -5-hydroxy-perhydro-cyclo-penta [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = H; the OH group at C-3 'is small in the alpha position.

800 mg of the small alpha alcohol obtained according to 5 b) were reacted with diisobutylaluminum hydride analogously to the procedure in Example 1 e). 750 mg of crude product were obtained.

d) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

The 750 mg of lactol obtained in c) were reacted without further purification analogously to the procedure in Example 1 f) with 5.1 g of 4-carboxybutyltriphenylphosphonium bromide and 22 ml of the methanesulfinylmethylsodium solution described there. Yield: 480 mg

c) The prostaglandic acid obtained according to d) was dissolved in methylene chloride and esterified with an ethereal diazomethane solution. The evaporation residue was chromatographed on silica gel using hexane / 50-95% ethyl acetate as the mobile phase.

The methyl prostaglandin carboxylate listed as Example 5 was obtained. Yield: 450 mg [small alpha] high 23 deep D = + 51.2 ° (c = 0.5; CHCl low 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 6

(5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

In the zinc borohydride reduction of (1S, 5R, 6R, 7R) -6 - [(E) -3-oxo-3 - ({2S} -1,3-benzodioxan-2-yl) described under Example 5 b) -1-propenyl] -7-benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one (Example 5 a) the small beta alcohol was eluted from the column as the 2nd product:

a) (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3-Hydroxy-3 - ({2S} -1,3-benzodioxan-2-yl) -1-propenyl] -7- benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one Yield: 0.7 g b) (2RS, 3aR, 4R, 5R, 6aS, 3'S) -4 - [(E) -3-hydroxy-3 - ({2S} -1,3-benzodioxan-2-yl) -1-propenyl] - 5-hydroxy-perhydro-cyclo-penta [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4, R deep5, R deep6 = H; the OH group at C-3 'is small in beta.

600 mg of the small beta alcohol obtained according to 6 a) were reacted with diisobutylaluminum hydride analogously to the procedure in Example 1 e). 470 mg of crude product were obtained.

c) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

The 470 mg lactol obtained in b) were reacted without further purification analogously to the procedure in Example 1 f) with 3.8 g of 4-carboxybutyltriphenylphosphonium bromide and 16.5 ml of the methanesulfinylmethylsodium solution described there. Yield: 330 mg d) The prostaglandic acid obtained according to c) was converted into the prostaglandin carboxylic acid methyl ester analogously to Example 5 e). Yield: 290 mg [small alpha] high 23 deep D = + 50 ° (c = 0.5; CHCl deep 3) IR: 3400 (wide), 1730, 1590, 1490, 980, 750 cm high -1

Example 7

(5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = O; R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

a) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-Hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] - 7-hydroxy-2-oxabicyclo [3.3.0] octan-3-one

A mixture of 1.97 g (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-hydroxy - ({2RS} -1,3-benzodioxan-2-yl) -1- propenyl] -7-benzoyloxy-2-oxa-bicyclo [3.3.0] octan-3-one (prepared according to Example 1d)) and 622 mg of potassium carbonate (anhydrous) in 91 ml of methanol (absolute) were stirred for 2 hours Room temperature below

Argon. Then it was poured into 90 ml of 0.1N hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with brine, dried with magnesium sulfate and evaporated in vacuo. After chromatography of the crude product on silica gel (ether / ethyl acetate = 7: 3), 1.20 g of a colorless oil were obtained.

b) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -3 ', 7 -bis- (tetrahydropyranyloxy) -2-oxabicyclo- [3.3.0] octan-3-one

6.1 ml of dihydropyran (freshly distilled) and 15 mg of p-toluenesulfonic acid were added to a solution of 1.85 g of the diol obtained according to a) in 50 ml of methylene chloride at ice bath temperature, the mixture was stirred for 15 'at this temperature, diluted with methylene chloride and shaken with sodium carbonate solution. The organic phase was washed with water, dried with magnesium sulfate and evaporated in vacuo. After chromatography on silica gel (ether), 2.2 g of bis-tetrahydropyranyl ether were obtained.

c) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -3 ' , 5-bis (tetrahydropyranyloxy) -perhydro-cyclopental [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4 = H; R low 5, R low 6 = THP; the OTHP group at C-3 'is small alpha.

22 ml of a 20% strength DIBAH solution in toluene were added dropwise under argon to a solution, cooled to -70 ° C., of 2.2 g of the lactone obtained in b) in 85 ml of absolute toluene. After 30 'the reaction was terminated by the dropwise addition of isopropanol and the mixture was stirred at 0 ° C. for 15' with the addition of 30 ml of water. It was then extracted with ethyl acetate, washed with brine, dried with magnesium sulfate and evaporated in vacuo. This gave 2.2 g of lactol as a colorless oil.

d) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9-hydroxy-11,15-bis (tetra-hydropyranyloxy) -15 - ({2RS} -1,3-benzodioxane-2 -yl) -16,17,18,19,20-pentanor-prostandienoic acid

To a solution of 9.5 g of 4-carboxybutyltriphenylphosphonium bromide in 40 ml of absolute dimethyl sulfoxide was added dropwise 34.7 ml of a solution of methanesulfinylmethyl sodium in absolute dimethyl sulfoxide (solution: 2.5 g of 50% sodium hydride suspension in 50 ml of absolute dimethyl sulfoxide for 1 hour at 70 ° Stir C) and stirred for 30 'at room temperature. This Ylene solution was then added dropwise at 15 ° C. to a solution of 2.16 g of the lactol obtained according to c) in 40 ml of absolute dimethyl sulfoxide over the course of 15 ′ and stirred at 50 ° C. for 2 hours. The solvent was then largely distilled off under an oil pump vacuum and 45 ° C., the residue was taken up in 80 ml of water and extracted three times with ether. Of the organic extract was discarded. The aqueous phase was acidified to pH 4-5 with 10% citric acid solution and extracted four times with a mixture of hexane / ether 1 + 1. The ether / hexane extract was washed with brine, dried with magnesium sulfate and evaporated in vacuo. After the evaporation residue was chromatographed on silica gel, 2.48 g of the acid were eluted as a colorless oil with ether.

e) (5Z, 13E) - (8R, 11R, 12R, 15R) -9-Oxo-11,15-bis (tetrahydropyranyloxy) -15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostadic acid

A solution of 2.35 g of the alcohol obtained according to d) in 30 ml of acetone was admixed with 2.46 ml of Jones reagent (J. Chem. Soc. 1953, 2555) at -20 ° C. and the mixture was stirred for 30 'at -20 ° C. Then 3 ml of isopropyl alcohol were added dropwise, the mixture was stirred for 10 'at -20 ° C., diluted with ether and shaken three times with water. The organic phase was dried with magnesium sulfate and evaporated in vacuo. 2.1 g of the ketone were obtained as a colorless oil. f) (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans, CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = O; R deep1 = OH; R deep2, R deep3, R deep4 = H;

the OH group at C-15 is small in the alpha position.

2.1 g of the bis-tetrahydropyranyl ether obtained according to e) were stirred for 5 hours at 70 ° C. in 42 ml of a mixture which consisted of 65 parts of glacial acetic acid, 35 parts of water and 10 parts of tetrahydrofuran. It was then evaporated to dryness at 0.1 torr and the crude product was purified by column chromatography. With chloroform / ethanol 95 + 5, 450 mg of the E deep2 derivative were eluted as a colorless oil.

g) To a solution of 130 mg of the acid obtained according to f) in 4 ml of methylene chloride was added dropwise at ice bath temperature 7 ml of an ethereal diazomethane solution, stirred for 2 'and then evaporated in vacuo. After chromatography of the crude product on silica gel (ether / dioxane 95: 5), in addition to mixed fractions, 56 mg of the methyl prostaglandin ester listed as Example 7 were obtained as an oil which was completely uniform by thin-layer chromatography. IR: 3400 (wide), 1740, 1730, 1590, 1490, 980, 750 cm high-1

Example 8

(5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

a) (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl-1-propenyl] -7-hydroxy -2-oxabicyclo [3,3,0] octan-3-one

2.16 g (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3-hydroxy - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -7- benzoyloxy-2-oxabicyclo [3.3.0] octan-3-one (prepared according to Example 2 a)) and 687 mg of anhydrous potassium carbonate were stirred in 99 ml of methanol at room temperature for 2.5 hours. 99 ml of 0.1 N HCl were then added, the mixture was stirred for 15 minutes, extracted with ethyl acetate, the organic phase was shaken with brine, dried and evaporated in vacuo. The crude product was chromatographed on silica gel. 1.38 g of the diol were obtained as a colorless oil. b) (1S, 5R, 6R, 7R, 3'S) -6 - [(E) -3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -3 ', 7-bis - (tetrahydropyranyloxy) -2-oxabicyclo [3.3.0] octan-3-one

4.5 ml of dihydropyran (freshly distilled) and 10 mg of p-toluenesulfonic acid, stirred at about 5 ° C. for 15 ', were added to a solution of 1.38 g of the diol obtained according to a) in 30 ml of methylene chloride with methylene chloride, shaken with sodium bicarbonate solution, with brine, dried with magnesium sulfate and evaporated in vacuo. After chromatography of the crude product on silica gel (ether / hexane 8: 2), 1.91 g of the bis-tetrahydropyranyl ether were obtained as a colorless oil.

c) (2RS, 3aR, 4R, 5R, 6aS, 3'S) -4 - [(E) -3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -3 ', 5 -bis- (tetrahydropyranyloxy) -perhydrocyclopenta [b] furan-2-ol

General formula II: A = trans CH = CH; R deep2, R deep3, R deep4 = H; R deep 5, R deep 6 = THP; the OTHP group at C-3 'is small beta.

In analogy to the procedure in Example 7c, 1.91 g of the lactone obtained according to b) were reduced in 75 ml of absolute toluene with 19 ml of diisobutylaluminum hydride (DIBAH) solution. Customary work-up gave 1.93 g of lactol as a colorless oil. d) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9-hydroxy-11,15-bis (tetrahydropyranyloxy) -15 - ({2RS} -1,3-benzodioxan-2-yl ) -16,17,18,19,20-pentanor-prostadienoic acid

In analogy to the procedure in Example 7 d), 1.93 g of the lactol obtained according to c) were prepared in 30 ml of absolute DMSO with a ylene solution made from 8.47 g of 4-carboxy-butyl-triphenylphosphonium bromide and 31 ml of methanesulfinylmethylsodium solution was implemented. After the usual work-up, the crude product was purified by column chromatography. 2.1 g of the acid were eluted as a colorless oil with ether.

e) (5Z, 13E) - (8R, 11R, 12R, 15S) -9-Oxo-11,15-bis (tetrahydropyranyloxy) -15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostadic acid

In analogy to the procedure in Example 7 e), 2.05 g of the alcohol obtained according to d) were oxidized in 50 ml of acetone with 2.14 ml of Jones reagent at -20.degree. After working up, 1.84 g of the ketone were obtained as a colorless oil.

f) (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OH, R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the beta position.

Analogously to the procedure in Example 7 f), 1.84 g of the bis-tetrahydropyranyl ether obtained according to e) were stirred with 18 ml of the acetic acid / THF mixture. After working up and chromatography on silica gel (chloroform / ethanol = 95/5), 528 mg of the E deep2 derivative were obtained as a colorless oil.

g) 98 mg of the prostaglandic acid obtained according to f) was converted into the prostaglandin carboxylic acid methyl ester analogously to Example 7 g). Yield: 76 mg IR: 3400 (broad), 1740, 1730, 1590, 1490, 980, 750 cm high-1

Example 9

(5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OCH deep3, OH; R deep2, R deep3, Rlow4 = H; the OH group at C-15 is small in the alpha position.

Production takes place analogously to Example 7 a) -g) from the starting compound produced according to Example 3 b). Yield 400 mg of prostate acid as a colorless oil, 60 mg of methyl prostate ester (prepared from 130 mg of acid) IR: 3500-3400, 1740, 1730, 1590, 1490, 980, 750 cm to the power of -1

Example 10

(5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19 , 20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

Production takes place analogously to Example 8 a) -g) from the starting compound produced according to Example 4 a). Yield: 510 mg of prostate acid as a colorless oil 70 mg of methyl prostate ester (from 100 mg of acid) IR: 3500-3400, 1740, 1730, 1590, 1490, 980, 750 cm to the power of -1

Example 11

(5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in the alpha position.

Production takes place analogously to Example 7 a) -g) from the starting compound produced according to Example 5 b). Yield: 310 mg of prostate acid as a colorless oil 50 mg of methyl prostate ester (from 120 mg of acid) IR: 3500-3400, 1740, 1730, 1590, 1490, 980, 750 cm to the power of -1

Example 12

(5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

Z = C = 0; R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in beta.

Production takes place analogously to Example 8 a) -g) from the starting compound produced according to Example 6 a). Yield: 410 mg of prostate acid, 150 mg of methyl prostate ester (from 210 mg of acid) IR: 3500 - 3400, 1740, 1730, 1590, 1490, 980, 750 cm to the power of -1

Example 13

(5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

a) (1S, 5R, 6R, 7R, 3'R) -6- [3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -7-benzoyloxy- 2-oxa-bicyclo [3.3.0] octan-3-one

2.3 g of the small alpha alcohol obtained according to Example 1 d) and 230 mg of palladium on carbon (10%) were shaken after 2 hours in 40 ml of ethyl acetate under a hydrogen atmosphere. Filtration and evaporation gave 2.3 g of the above alcohol as a colorless oil. IR: 3600, 1775, 1720, 1590, 1490, 770 cm high -1. No olefinic protons were recognizable in the NMR spectrum.

b) (1S, 5R, 6R, 7R, 3'R) -6- [3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -7-hydroxy- 2-oxa-bicyclo [3.3.0] octan-3-one

From 2.20 g of the saturated alcohol obtained according to a), 1.34 g of the saturated diol were obtained as a colorless oil by transesterification according to Example 7 a). IR: 3600 strong, 1775, 1590, 1490, 760 cm high-1 c) (1S, 5R, 6R, 7R, 3'R) -6- [3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -3 ', 7-bis (tetrahydropyranyloxy ) -2-oxabicyclo [3,3,0] octan-3-one

From 1.13 g of the diol obtained according to b), 1.08 g of the above bis (tetrahydropyranyl) ether was obtained as a colorless oil with dihydropyran analogously to Example 7 b). IR: 1775, 1590, 1490, 1100, 760 cm high -1

d) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4- [3- {2RS} -1,3-benzodioxan-2-yl) -1-propyl] -3,5-bis (tetrahydropyranyloxy ) -perhydro-cyclo-penta [b] furan-2-ol

General formula II: A = CH deep 2-CH deep 2; R deep 2, R deep 3, R deep 4 = H; R deep 5, R deep 6 = THP; the OTHP group at C-3 'is small alpha.

According to Example 7 c), by reducing 1.08 g of the bis (tetrahydropyranyl) ether prepared according to c), 1.06 g of the above lactol was obtained as a colorless oil. IR: 3600, 1590, 1490, 1100, 760 cm high -1

e) (5Z) - (8R, 9S, 11R, 12R, 15R) -9-hydroxy-11,15-bis (tetrahydropyranyloxy) -15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostenic acid

1.06 g of the lactol obtained according to d) were converted according to Example 7 d) into 866 mg of the abovementioned prostate acid. IR: 3600-3400, 1710, 1590, 1490, 1100, 760 cm high-1 f) (5Z) - (8R, 9S, 11R, 12R, 15R) -9-11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid

310 mg of the compound obtained according to e) were stirred at 50 ° C. for 3 hours in 9 ml of a mixture of acetic acid / water / tetrahydrofuran = 65/35/10. It was evaporated to dryness in vacuo and, after chromatography on 10 g of silica gel (chloroform / ethanol 4 + 1), 211 mg of the above compound were obtained as a colorless oil. IR: 3600-3300, 1710, 1590, 1490, 760 cm high-1

g) To a solution of 130 mg of the acid obtained according to f) in 4 ml of methylene chloride, 7 ml of an ethereal diazomethane solution were added dropwise at ice bath temperature, the mixture was stirred for 15 minutes and then evaporated in vacuo. After chromatography of the crude product on silica gel (methylene chloride) 3% isopropanol, 90 mg of the prostaglandin carboxylic acid methyl ester listed as Example 13 were obtained. IR: 3600-3300, 1730, 1590, 1490, 760 cm high-1

Example 14

(5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

a) (1S, 5R, 6R, 7R, 3'S) -6- [3-Hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -7-benzoyloxy-2- oxabicyclo [3.3.0] octan-3-one

Analogously to Example 13 a), 2.4 g of the small beta alcohol obtained according to Example 2 a) were hydrogenated to 2.4 g of the abovementioned saturated alcohol. A colorless oil was obtained. IR: 3600, 1775, 1720, 1590, 1490, 770 cm high -1

b) (1S, 5R, 6R, 7R, 3'S) -6- [3-hydroxy-3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -7-hydroxy-2- oxabicyclo [3.3.0] octan-3-one

From 2.3 g of the saturated alcohol obtained according to a), 1.39 g of the saturated diol were obtained as a colorless oil by transesterification with potassium carbonate according to Example 7 a). IR: 3600 strong, 1775, 1590, 1490, 760 cm high-1 c) (1S, 5R, 6R, 7R, 3'S) -6- [3 - ({2RS} -1,3-benzodioxan-2-yl) -1-propyl] -3 ', 7-bis (tetrahydropyranyloxy) - 2-oxa-bicyclo- [3.3.0] octan-3-one

From 1.0 g of the diol prepared according to b), using dihydropyran analogously to Example 7 b), 0.93 g of the above bis (tetrahydropyranyl) ether was obtained as a colorless oil. IR: 1775, 1590, 1490, 1100, 760 cm high -1

d) (2RS, 3aR, 4R, 5R, 6aS, 3'S) -4- [3- {2RS} -1,3-benzodioxan-2-yl) -1-propyl] -3 ', 5-bis (tetrahydropyranyloxy) -perhydro-cyclo-penta [b] furan-2-ol

According to Example 7 c), by reducing 0.74 g of the bis (tetrahydropyranyl) ether prepared according to c), 0.7 g of the above lactol was obtained as a colorless oil. IR: 3600, 1590, 1490, 1100, 760 cm high -1

e) (5Z) - (8R, 9S, 11R, 12R, 15S) -9-hydroxy-11,15-bis (tetrahydropyranyloxy) -15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostenic acid

0.7 g of the lactol obtained according to d) were converted according to Example 7 d) into 0.51 g of the abovementioned prostate acid. IR: 3600-3400, 1710, 1590, 1490, 1100, 760 cm high-1 f) (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid

Analogously to the procedure in Example 13 f), 219 mg of the above compound were obtained as a colorless oil from 345 mg of the triol obtained according to e). IR: 3600-3300, 1710, 1590, 1490, 760 cm high-1

g) Analogously to the esterification described in Example 13 g), 85 mg of the methyl prostaglandin carboxylate listed as Example 14 were obtained from 120 mg of the acid obtained according to f). IR: 3600-3300, 1730, 1590, 1490, 755 cm high-1

Example 15

(5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2, B = cis CH = CH; XY = CH deep2

R deep2 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position

Starting from the small alpha alcohol obtained according to Example 3 b), the title compounds were obtained analogously to the reaction steps described for Example 13 a) -g). IR: 3500-3300, 1730, 1590, 1490, 760 cm high-1

Example 16

(5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

Starting from the small beta alcohol obtained according to Example 4 a), the title compounds were obtained analogously to the reaction stages described for Example 14 a) -g). IR: 3400 (wide), 1730, 1590, 1490, 760 cm high-1

Example 17

(5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

Starting from the small alpha alcohol obtained according to Example 5 b), the title compounds were obtained analogously to the reaction steps described for Example 13 a) -g). IR: 3400 (wide), 1735, 1590, 1490, 760 cm high-1

Example 18

(5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid and methyl ester General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

Starting from the small beta alcohol obtained according to Example 6 a), the title compounds were obtained analogously to the reaction stages described for Example 14 a) -g). IR: 3400 (wide), 1735, 1590, 1490, 760 cm high-1

Example 19

(5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in the alpha position.

a) (5Z) - (8R, 11R, 12R, 15R) -11,15-bis (tetrahydro-pyranyloxy) -9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16 , 17,18,19,20-pentanor-prostenic acid

300 mg of the compound obtained according to Example 13 e) were converted into the abovementioned compound by oxidation analogously to Example 7 e) and 210 mg were obtained as a colorless oil. IR: 3600-3300, 1740, 1710, 1590, 1490, 760 cm high-1

b) (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid

According to Example 7 f), 90 mg of the abovementioned compound were obtained as a colorless oil from 150 mg of the compound obtained according to a). IR: 3600-3400, 1740, 1710, 1590, 1490, 760 cm high-1 c) Analogously to Example 7 g), 75 mg of the methyl prostaglandin carboxylate were obtained from 90 mg of the acid obtained according to b). IR: 3600-3400, 1740, 1730, 1590, 1490, 750 cm high-1

Example 20

(5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in beta.

a) (5Z) - (8R, 11R, 12R, 15S) -11,15-bis (tetrahydro-pyranyloxy) -9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16 , 17,18,19,20-pentanor-prostenic acid

280 mg of the compound obtained according to Example 14 e) were converted into the abovementioned compound by oxidation analogously to Example 7 e). 180 mg were obtained as a colorless oil. IR: 3600-3300, 1740, 1710, 1590, 1490, 760 cm high-1 b) (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid

According to Example 7 f), 145 mg of the compound obtained according to a) were converted to 80 mg of the abovementioned diol. IR: 3600-3400, 1740, 1710, 1590, 1490, 755 cm high-1

c) Analogously to Example 7 g), 56 mg of the stated methyl prostaglandin carboxylate were obtained from 80 mg of the acid obtained according to b). IR: 3600-3400, 1740, 1730, 1590, 1490, 755 cm high-1

Example 21

(5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in the alpha position.

Starting from the derivative of Example 15 corresponding to 13 e), the title compounds were obtained analogously to the reaction steps described for Example 19 a) -c). IR: 3500 - 3400, 1740, 1730, 1590, 1490, 750 cm high -1

Example 22

(5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in beta.

Starting from the derivative of Example 16 corresponding to 14 e), the title compounds were obtained analogously to the reaction steps described for Example 19 a) -c). IR: 3600-3400, 1740, 1730, 1590, 1490, 755 cm high-1

Example 23

(5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep 2, R deep 3, R deep 4 = H; the OH group at C-15 is small in the alpha position.

Starting from the derivative of Example 17 corresponding to 13 e), the title compounds were prepared analogously to the reaction steps described for Example 19 a) -c). IR: 3600-3400, 1740, 1730, 1590, 1490, 755 cm high-1

Example 24

(5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = CH deep2-CH deep2; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

Starting from the derivative of Example 18 corresponding to 14 e), the title compounds were prepared analogously to the reaction steps described for Example 19 a) -c). IR: 3500 - 3400, 1740, 1730, 1590, 1490, 750 cm high -1

Example 25

(5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

A solution of 88 mg (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16 , 17,18,19,20-pentanor-prostadienoic acid (from Example 7 f) in 6 ml of 90%

Acetic acid was stirred at 60 ° C. for 19 hours and then evaporated in vacuo. After chromatography on silica gel (ether / 3% dioxane), the prostatric acid was etherified with an ethereal diazomethane solution. 45 mg of the title compound were obtained as a pale yellow oil. IR: 3600 - 3300, 1730, 1700, 1590, 1490, 980, 760 cm high-1

Example 26

(5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

According to the procedure described in Example 25, the title compounds were prepared from the compound described in Example 8 f). IR: 3500-3300, 1730, 1705, 1590, 1490, 980, 760 cm high-1

Example 27

(5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

According to the procedure described in Example 25, the title compounds were prepared from the compound described in Example 9 f). IR: 3600-3300; 1730, 1700, 1585, 1490, 980, 760 cm high-1

Example 28

(5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

According to the procedure described in Example 25, the title compounds were prepared from the compound described in Example 10 f). IR: 3600 - 3300, 1730, 1700, 1590, 1490, 980, 760 cm high-1

Example 29

(5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

According to the procedure described in Example 25, the title compounds were prepared from the compound described in Example 11 f). IR: 3500 - 3300, 1730, 1700, 1590, 1485, 980, 760 cm high-1

Example 30

(5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostatrienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH = CH;

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in beta.

According to the procedure described in Example 25, the title compounds were prepared from the compound described in Example 12 f). IR: 3600 - 3300, 1730, 1700, 1590, 1490, 980, 760 cm high-1

Example 31

(13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

General formula I: A = trans CH = CH; B = CH deep2-CH deep2; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

150 mg of the compound obtained according to Example 1 f) or 1 g) were mixed with 15 mg of 10% palladium on carbon and stirred with 15 ml of ethyl acetate for 2 hours at -20 ° C. under a hydrogen atmosphere. After filtration, the mixture was evaporated to dryness in vacuo and 140 mg of the title compound were obtained as a colorless oil. IR: 3600-3300, 1730, 1590, 1490, 980, 760 cm high -1 The NMR spectrum shows only two olefinic protons.

Example 32

Analogously to Example 31, from the corresponding starting compounds 2 d), 3 e), 4 d), 5 e), 6 d)

(13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

(13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20- Pentanor-prostenic acid and methyl esters (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17 , 18,19,20-pentanor-prostenic acid and methyl ester (13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxane-2 -yl) -16,17,18,19,20-pentanorpropenoic acid and methyl ester (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2S} - 1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostenic acid and methyl ester

getting produced.

Example 33

If, in the reaction sequence leading to the compounds of Examples 7-12, a reduction of the compounds 7 d), 8 d), 9 d), 10 d), 11 d), 12 d) analogously to the process described for Example 31 is interposed, so the following connections are obtained:

(13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor prostenic acid and methyl ester

(13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid and methyl ester (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostenic acid and methyl ester (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1 , 3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostenic acid and methyl ester (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo -15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostenic acid and methyl ester (13E) - (8R, 11R, 12R, 15S) - 11,15-Dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostenic acid and methyl ester

Example 34

(8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid and methyl esters

General formula I: A = B = CH deep2-CH deep2; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

432 mg of the ester or the acid obtained according to Example 1, 45 mg of palladium on carbon (10%) and 10 ml of ethyl acetate were shaken at room temperature in a hydrogen atmosphere until 2 mmol of hydrogen were absorbed. After filtration and evaporation, 420 mg of the above compound were obtained as a colorless oil. IR: 3600-3400, 1730, 1590, 1490, 760 cm high-1

Example 35

Analogously to the process described in Example 34, the following derivatives were obtained with the compounds of Examples 2-6:

(8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- Prostanoic acid and methyl esters (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19 , 20-pentanorprostanoic acid and methyl ester (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16, 17,18,19,20-pentanor-prostanoic acid and methyl esters (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxane-2- yl) -16,17,18,19,20-pentanor-prostanoic acid and methyl ester

(8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid and methyl esters

Example 36

(5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

a) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-tetrahydropyranyloxy-3- {2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -7 -benzoyloxy-2-oxabicyclo- [3.3.0] octan-3-one

3 ml of dihydropyran (freshly distilled) and 10 mg of p-toluenesulfonic acid were added to a solution of 2.4 g of the small alpha alcohol obtained according to Example 1 d) in 50 ml of methylene chloride at ice bath temperature, and the mixture was stirred at this temperature for 15 minutes Methylene chloride and shaken with sodium bicarbonate solution. The organic phase was washed with water, dried with magnesium sulfate and evaporated in vacuo. 2.8 g of product were obtained. b) (1S, 5R, 6R, 7R, 3'R) -6 - [(E) -3-tetrahydropyranyloxy-3- {2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -7 -hydroxy-2-oxabicyclo- [3.3.0] octan-3-one

A mixture of the 2.8 g obtained according to a) and 765 mg of potassium carbonate (anhydrous) in 110 ml of methanol (absolute) was stirred for 2 hours at room temperature under argon. Then it is diluted with ethyl acetate and washed neutral with saturated sodium chloride solution. The organic phase was dried over magnesium sulfate and evaporated in vacuo. 1.85 g of the title compound were obtained.

c) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-tetrahydropyranyloxy-3- {2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -5-hydroxy-perhydrocyclopenta [b] -furan-2-ol

To a solution, cooled to -70 ° C., of 1.85 g of the lactone obtained according to b) in 90 ml of absolute toluene, 22 ml of a 20% strength DIBAH solution in toluene were added dropwise under argon. After 30 'the reaction was terminated by the dropwise addition of isopropanol and the mixture was stirred at 0 ° C. for 15' with the addition of 30 ml of water. It was then extracted with ethyl acetate, washed with brine, dried with magnesium sulfate and evaporated in vacuo. 1.8 g of the title compound were obtained as a colorless oil. d) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-tetrahydropyranyloxy-3- {2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -2,5-diacetoxy-perhydro-cyclopenta [b] furan-2-ol

1.8 g of the lactol obtained according to c) were stirred in a mixture of 10 ml of acetic anhydride and 25 ml of pyridine for 8 hours at room temperature. After removing the solvent in vacuo, 2.0 g of the title compound were obtained.

e) (2RS, 3aR, 4R, 5R, 6aS, 3'R) -4 - [(E) -3-tetrahydropyranyloxy-3- {2RS} -1,3-benzodioxan-2-yl) -1-propenyl] -5-acetoxy-perhydro-cyclopenta [b] furan-2-ol

2.0 g of the diacetate obtained according to d) were kept at 25 ° C. in a mixture of 5 parts of glacial acetic acid, 5 parts of water and one part of tetrahydrofuran 15 ', then stirred into a sodium hydrogen carbonate solution and washed until neutral. The organic phase was concentrated and the residue was purified by column chromatography on silica gel with ether / pentane = 1/1. 1.5 g of the title compound were obtained.

f) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9-hydroxy-11-acetoxy-15-tetrahydropyranyloxy-15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostadic acid

26.3 ml of a solution of methanesulfinylmethylsodium were added dropwise to a solution of 7.2 g of 4-carboxybutyltriphenylphosphonium bromide in 30 ml of absolute dimethyl sulfoxide in absolute DMSO (solution: 2.5 g of 50% sodium hydride suspension in 50 ml of DMSO for 1 hour at 70 ° C.) and stirred for 30 'at room temperature. This Ylene solution was then added dropwise at 15 ° C. to a solution of 1.5 g of the lactol obtained according to e) in 30 ml of absolute DMSO over the course of 15 'and stirred at 50 ° C. for 2 hours. The solvent was then largely distilled off under an oil pump vacuum and 45 ° C., the residue was taken up in 70 ml of water and extracted three times with ether. The organic extract was discarded. The aqueous phase was acidified to pH 4-5 with 10% citric acid solution and extracted four times with a mixture of hexane / ether = 1/1. The ether / hexane extract was washed with brine, dried over magnesium sulfate and evaporated in vacuo. After chromatography of the residue on silica gel, 1.1 g of the title compound was eluted as a colorless oil with ether.

g) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,15-bis (tetrahydropyranyloxy) -11-acetoxy-15 - ({2RS} -1,3-benzodioxan-2-yl ) -16,17,18,19,20-pentanor-prostadienoic acid

A methylene chloride solution of 1.1 g of the compound obtained according to f) was mixed with 2.2 ml of dihydropyran and 6 mg of p-toluenesulfonic acid at ice bath temperature and stirred for 15 'at this temperature. Then with

Diluted methylene chloride, shaken with sodium bicarbonate solution, washed the organic phase with water, dried over magnesium sulfate and concentrated. The residue was treated for 15 'at 25 ° C. with a glacial acetic acid / water / THF mixture (5/5/1), then stirred into a sodium bicarbonate solution and washed neutral. After concentrating the organic phase, 1.2 g of a colorless oil were obtained.

h) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,15-bis (tetrahydropyranyloxy) -11-hydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl ) -16,17,18,19,20-pentanor-prostadienoic acid

The 1.2 g obtained from g) were reacted with potassium carbonate and methanol analogously to the procedure described in b). 0.8 g of the title compound was obtained.

i) (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-bis (tetrahydropyranyloxy) -11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) - 16,17,18,19,20-pentanor-prostadic acid

A solution of 0.8 g of the alcohol obtained according to h) in 10 ml of acetone was mixed with 0.84 ml of Jones reagent at -20.degree. C. and the mixture was stirred at -20.degree. C. for 30 minutes. Then 1 ml of isopropanol was added dropwise, the mixture was stirred for 10 'at -20 ° C., diluted with ether and shaken out three times with water. The organic phase was dried over magnesium sulfate and evaporated in vacuo. 725 mg of the ketone were obtained as a colorless oil. j) (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid

650 mg of the bis-tetrahydropyranyl ether prepared according to i) were stirred for 6 hours at 50 ° C. in 15 ml of a mixture which consisted of 65 parts of glacial acetic acid, 35 parts of water and 10 parts of tetrahydrofuran. It was then evaporated to dryness at 0.1 torr and the crude product was purified by column chromatography. 280 mg of the title compound were eluted with methylene chloride / 5-8% ethanol.

k) To a solution of 140 mg of the acid obtained according to j) in 10 ml of methylene chloride, 7 ml of an ethereal diazomethane solution were added dropwise at ice bath temperature, the mixture was stirred for 10 'and then evaporated in vacuo. After chromatography of the crude product on silica gel with ether / dioxane = 95/5 as the flow agent, 80 mg of the prostaglandin carboxylic acid methyl ester of the D-type listed as Example 36 were obtained. IR: 3500-3300, 1740, 1730, 1590, 1485, 980, 760 cm high-1

Example 37

Analogously to the process described in Example 36, starting from the compounds of Examples 2 a), 3 b), 4 a), 5 b) and 6 a), the following derivatives were obtained:

(5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid and methyl ester (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2R} -1,3-benzodioxane-2 -yl) -16,17,18,19,20-pentanor-prostadienoic acid and methyl ester (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({ 2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostadienoic acid and methyl ester (5Z, 13E) - (8R, 9S, 12R, 15R) -9.15- Dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostadienoic acid and methyl ester (5Z, 13E) - (8R, 9S , 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor-prostadienoic acid and methyl ester

Example 38

(5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-6-bromo-2-yl) -16, 17,18,19,20-pentanor prostadienoic acid and methyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep1 = OCH deep3, OH; R deep2, R deep4 = H; R deep3 = Br (p-position to the phenolic oxygen); the OH group at C-15 is small in the alpha position. a) 5-bromo-2-hydroxy-benzyl alcohol To a suspension of 24.8 g of saligenin and 24 g of calcium carbonate in a solvent mixture of 200 ml of carbon tetrachloride and 220 ml of methylene chloride were at 0-5 ° C 11.5 ml of bromine in 100 ml of carbon tetrachloride dripped. The reaction mixture was stirred at room temperature for 24 hours, then filtered and the precipitate washed with carbon tetrachloride. The CCl deep4 / CH deep2 Cl deep2 phase was discarded. The solid was taken up in ethyl acetate / water, the organic phase was separated off, dried over magnesium sulfate and concentrated to dryness. The residue was recrystallized from methylene chloride. Leaf-shaped, colorless crystals (24 g) were obtained. Melting point: 107 - 109 ° C (methylene chloride)

b) 1,3-Benzodioxane-6-bromo-2-carboxylic acid methyl ester To a suspension of 9.6 g of 50% sodium hydride in 100 ml of dimethylformamide, a solution of 20.3 g of the according to a ) 5-bromo-2-hydroxybenzyl alcohol obtained was added dropwise to 110 ml of dimethylformamide. The reaction mixture was stirred at room temperature overnight. Then 8.62 ml of dichloroacetic acid were added dropwise to 100 ml of dimethylformamide while cooling with ice. 5.04 g of 50% strength sodium hydride were then added in portions while cooling with ice. This sodium dichloroacetate solution was stirred for 30 minutes at room temperature and then added dropwise to the bromosaligenin disodium solution prepared first. After the addition of 1.5 g of sodium iodide, the reaction mixture was stirred for 4.5 hours at 60 ° C., during the last 2.5 hours most of the dimethylformamide was distilled off in vacuo. After cooling, the residue was acidified with aqueous citric acid solution to pH = 3, saturated with sodium chloride and extracted several times with methylene chloride. The organic phase was dried over magnesium sulphate, concentrated on a rotary evaporator and ethereal diazomethane solution was added at 0 ° C. until no more gas evolution occurred and the reaction solution remained yellow. The solvent was removed together with excess diazomethane after half an hour of stirring at room temperature in vacuo. The remaining pale crystal pulp was purified by column chromatography on silica gel using methylene chloride or hexane / 10% ethyl acetate as the mobile phase. Yield: 12.6 g Melting point: 120 ° C (matted small needles made from methylene chloride / hexane) c) [2-Oxo-2- (1,3-benzodioxan-6-bromo-2-yl) ethylidene] triphenylphosphorane To a suspension of 13 g of triphenylmethylphosphonium bromide (dried on an oil pump at 40 ° C. for 4 hours) in 85 15.63 ml of a 2.15 M butyllithium solution in hexane were added dropwise with ice-cooling and in an argon atmosphere, and the mixture was then stirred for 15 hours at room temperature. 4.59 g of the 1,3-benzodioxane-6-bromo-2-carboxylic acid methyl ester obtained according to b) in 75 ml of absolute benzene were added dropwise to the yellow Ylene solution, the mixture was stirred at room temperature for 1 hour, the white precipitate was filtered off, dissolved in water and extracted with ether. The organic phase was combined with the filtrate, washed with water, dried over magnesium sulfate and concentrated to dryness. The residue was purified by column chromatography on silica gel with hexane / 20-100% ethyl acetate. Yield: 5.6 g Melting point: 172 ° - 174 ° C (ethyl acetate)

The other reaction cuts were carried out analogously to the instructions in 1 c) -g). All other prostaglandic acids and esters described in the present examples can also be converted into the derivatives corresponding to example 38 in an analogous manner.

Example 39

(5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid- (4-phenyl) -phenacyl ester

General formula I: A = trans CH = CH; B = cis CH = CH; XY = CH deep2

R deep2, R deep3, R deep4 = H; the OH group at C-15 is small in the alpha position.

75 mg of the prostatic acid obtained according to Example 1 f) were stirred with 21 mg of triethylamine and 53 mg of p-phenylphenacyl bromide in 4 ml of acetone for 12 hours at room temperature under argon. After dilution with water, it was extracted with ether, the ether extract was shaken with saline solution, dried over magnesium sulphate and evaporated in vacuo. The residue was filtered through 5 g of silica gel with ether / dioxane mixtures. After recrystallization from methylene chloride / hexane, 55 mg of the title compound were obtained as colorless crystals. Melting point: 118 ° C IR: 3600, 1740, 1695, 1590, 1490, 980, 750 cm high -1

In analogy to Example 39, all of the other prostaglandic acids described in the preceding examples can also be converted into the corresponding phenacyl esters.

Example 40

Tris (hydroxymethyl) aminomethane salt of (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl ) -16,17,18,19,20-pentanor-prostadienoic acid

A solution of 32.9 mg of tris (hydroxymethyl) aminomethane in 0.1 ml of water was added at 60 ° C. to a solution of 103 mg of the prostatic acid prepared according to Example 1 f) in 14 ml of acetonitrile and left at room temperature for 14 hours stand. 76 mg of the above salt were obtained as colorless crystals.

In analogy to Example 40, all of the other prostaglandic acids described in the preceding examples can also be converted into the corresponding tris (hydroxymethyl) amino methane salts.

Claims (61)

1. 1,3-Benzodioxan-prostanoic acid derivatives of the general formula I and their antipodes and racemates wherein R deep 1 is a hydroxyl group, a straight or branched alkoxy group with 1 - 10 carbon atoms, a methylsulfamide group, a substituted or unsubstituted aryloxy group, an O-CH deep 2-UV group, where U is a direct bond, a carbonyl or carbonyloxy group and V denotes a phenyl ring substituted by one or more phenyl groups, alkoxy groups with 1-2 carbon atoms or halogen atoms, preferably bromine atoms A denotes a CH deep2-CH deep2 or a trans -CH = CH group B denotes a -CH deep2-CH deep2- or a cis- or trans-CH = CH group, Z represents a hydroxymethylene or a carbonyl group, X ... Y for -CH deep 2 stands when Z is a hydroxymethylene group or -CH deep2 or -CH = CH- if Z is a carbonyl group, R deep2 denotes a hydrogen atom or an alkyl group with 1 - 5 carbon atoms, R deep 3 and R deep 4 are the same or different and represent H, F, Cl, Br, J, CF deep 3, CH deep 3 or alkoxy groups with 1 - 2 carbon atoms and if R deep 1 represents a hydroxyl group, the salts with physiologically acceptable bases . 2) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 3) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 4) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 5) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 6) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 7) (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 8) (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 9) (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 10) (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 11) (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 12) (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 13) (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 14) (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 15) (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 16) (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 17) (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 18) (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 19) (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 20) (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 21) (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 22) (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 23) (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 24) (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 25) (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 26) (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 27) (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 28) (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 29) (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 30) (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 31) (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostatrienoic acid 32) (13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 33) (13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 34) (13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid 35) (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid 36) (13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid 37) (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid 38) (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 39) (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 40) (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 41) (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 42) (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 43) (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostenic acid 44) (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 45) (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 46) (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 47) (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 48) (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 49) (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostanoic acid 50) (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 51) (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 52) (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 53) (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 54) (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 55) (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadic acid 56) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-6-bromo-2-yl) - 16,17,18,19,20-pentanor-prostadic acid 57) (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16.17, 18,19,20-pentanor-prostadienoic acid- (4-phenyl) -phenacyl ester 58) Tris (hydroxymethyl) aminomethane salt of (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxane-2 -yl) -16,17,18,19,20-pentanor-prostadienoic acid 59) methyl and p-phenylphenacyl esters of (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (5Z, 10Z, 13E) - (8R, 12S, 15R) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (5Z, 10Z, 13E) - (8R, 12S, 15S) -15-Hydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostatrienoic acid (13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostenic acid (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostenic acid (13E) - (8R, 9S, 11R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostenic acid (13E) - (8R, 9S, 11R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20- pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15R) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (13E) - (8R, 11R, 12R, 15S) -11,15-dihydroxy-9-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19, 20-pentanor-prostenic acid (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (8R, 9S, 11R, 12R, 15S) -9,11,15-trihydroxy-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18,19,20-pentanor- prostanoic acid (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2RS} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2R} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 12R, 15R) -9,15-dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 12R, 15S) -9,15-dihydroxy-11-oxo-15 - ({2S} -1,3-benzodioxan-2-yl) -16,17,18, 19,20-pentanor-prostadienoic acid (5Z, 13E) - (8R, 9S, 11R, 12R, 15R) -9,11,15-trihydroxy-15 - ({2RS} -1,3-benzodioxan-6-bromo-2-yl) -16, 17,18,19,20-pentanor-prostadic acid 60) Process for the preparation of the new 1,3-benzodioxanprostanoic acids of the general formula I, characterized in that a lactol of the general formula II where R deep 2, R deep 3, R deep 4 and A have the meaning given above and R deep 5 and R deep 6 denote a hydrogen atom or a hydroxyl protecting group, with a Wittig reagent of the general formula III Ph deep3 P = CH- (CH deep2) deep3-COR deep1 III. where Ph is a phenyl group and R deep 1 has the meaning given above, after which, if desired, after oxidation of the 9-hydroxy group, any hydroxyl protective groups present are split off again and then depending on the ultimately desired meaning of R deep 1, R deep 2, R deep 3, R deep 4 , R deep 5, R deep 6, A, B, XY and Z in the end product, optionally in any order, esterified a free 1-carboxy group or saponified an esterified 1-carboxy group and / or a 9-keto group is reduced and / or a 5,6 double bond is hydrogenated and / or a 13,14 and 5,6 double bond is hydrogenated and / or a 9-keto compound is dehydrated with elimination of the 11-hydroxy group and / or a 9-hydroxy group is oxidized after intermediate protection of the 11- and 15-hydroxy group and / or an 11-hydroxy group is oxidized after intermediate protection of the 9- and 15-hydroxy group and, if appropriate, a 1-carboxy compound is converted into a physiologically acceptable salt with a base and, if appropriate, the Racemate separates. 61) Medicines based on the compounds of general formula I.