IE73476B1

IE73476B1 - Cyclopentane derivatives process for their production and their pharmaceutical use

Info

Publication number: IE73476B1
Application number: IE265591A
Authority: IE
Inventors: Ulrich Dr Klar; Hartmut Dr Rehwinkel; Helmuet Prof Vorbruggen; Karl-Heinz Dr Thierauch; Peter Dr Verhallen
Original assignee: Schering Ag
Priority date: 1990-07-27
Filing date: 1991-07-29
Publication date: 1997-06-04
Also published as: EP0541593B1; CA2088159A1; DE59106490D1; WO1992002494A1; ZA915903B; GR3018360T3; IL98969A0; EP0541593A1; AU8227491A; DK0541593T3; JPH05509090A; DE4024345A1; ES2080956T3; PT98465A; IE912655A1; ATE127788T1; PT98465B

Abstract

The invention relates to cyclopentane derivatives of formula (I) in which there is a double bond between the carbon atoms of centres a-b or b-c, and their salts with physiologically tolerable bases, and $g(a), $g(b) or $g(g)-cyclodextrin clathrates and the liposome-encapsulated compounds of formula (I), process of producing them and their pharmaceutical use.

Description

The invention relates to cyclopentene derivatives, to processes for their manufacture and to their use as auxiliaries in pharmacological investigations and as medicaments. In recent years, intensive work has been done on cyclopentane derivatives, since prostaglandins derived from the cyclopentane system, such as, for example, PGA2, PGB2, PGE2, 6-oxo-PGEi, PGD2, PGFaa and PGJ2 and their analogues have a very wide range of biological effects, for example on the cardiovascular system, the central nervous system or the immune system.

It has been found, surprisingly, that by introducing a double bond in position 9 or 10 (prostaglandin numbering) of the prostane structure, in combination with a wide variety of structural features in the lower chain and in position 11, it is possible to obtain chemically and metabolically stable prostaglandin analogues that are capable of antagonising at the receptor the pharmacological properties of the unstable compound thomboxane-A2 (TXA2) or PGH2 and its stable analogues, such as, for example, U46619 or U44069.

The compounds of the present invention are therefore valuable auxiliaries for the selective treatment of disorders that can be attributed to an excess of TXA2 or PGH2.

The invention relates to cyclopentene derivatives of the formula I wherein Rl can be COOR4, wherein R4 can represent hydrogen, or optionally halo-, phenyl-, Ci-C4alkoxy- or di-(Cx-C4)alkylaminosubstituted Ci-Cioalkyl, C3-C10cycloalkyl or C7-C16aralkyl, Y-substituted phenacyl or C6-Ci2aryl, or a 5- or 6-membered heterocyclic radical having at least one N, O or S atom, or R1 can be -CONHR6, in which R6 represents hydrogen, Ci-Cioalkyl, C!-C10alkanoyl, C6-Ci 2arylsulphonyl or Ci-Cxoalkanesulphonyl, X represents -(CH2)p-, -CH2-O- or -CH2-S-, Z and A, each independently of the other, represent a direct bond, (Z)-CH=CH-, (E)-CH=CH- or -C=C-, p is from 0 to 5, n and r, each independently of the other, are from 0 to 2, R2 represents OR5 or R5, W represents a direct bond, a group - [ (CH2)n-V] q-, a group - (CH2) n-V-(CH2) q-V-, a free or functionally modified hydroxymethylene group or a free or functionally modified group, it being possible for the hydroxy group in each case to be in the a- or β-configuration, q is 1 or 2, D represents a direct bond, a straight-chained, saturate»? alkylene group having from 1 to 5 carbon atoms, a branched, saturated alkylene group or a straight-chained or branched, unsaturated alkylene group having from 2 to 5 carbon atoms, each of which may optionally be substituted by fluorine atoms; or -(CH2)n-NH-S02-, H · ~(CH2)n\ Η Η H H H Η H Η H V represents an 0 or S atom, E represents a direct bond, -CsC- or -CH=CR7-, wherein R7 can be hydrogen, Ci~Csalkyl, halogen or trifluoromethyl, AWDE together can be a direct bond, AW together can be a direct bond, DE together can be a direct bond, R3 -(CH2)7 -(CH2) m Ca-Ciocycloalkyl or optionally Y-substituted Ci-CiOalkyl, wherein R3 can be —(CH^- only if A or W represents a direct bond, m is 1 or 2, γ1 and Y2 are identical or different and represent Y, Y represents hydrogen, halogen, N3, CF3, ORS, NO2, NH2/ CN, COORS or Cj-Cioalkyl, R5 can be hydrogen, or optionally halo-substituted Ci-C10alkyl, C6-Ci2aryl or C7-C16aralkyl, and, when R4 represents hydrogen, the salts thereof with physiologically tolerable bases, as well as α-, β- or γ-cyclodextrin clathrates, and the compounds of the formula I encapsulated with liposomes.

The definition 5- or 6-membered heterocyclic radical relates to heterocycles that contain at least one hetero atom, preferably nitrogen, oxygen or sulphur, and are monoor bi-cyclic. There may be mentioned by way of example 2- furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, quinolyl and isoquinolyl.

Suitable alkyl groups R3, R4, R5, E and Y are straightchained or branched-chained alkyl groups having from 1 to 10 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, heptyl, hexyl and decyl.

The alkyl groups R3, R4, Rs, E and Y may be substituted by halogen atoms, dimethylamino, diethylamino, methoxy or ethoxy.

Preferred alkyl groups R3, R4, R5, E and Y are those having from 1 to 5 carbon atoms, such as, for example, methyl, ethyl, propyl, isobutyl, butyl, neopentyl, tert-butyl, chloroethyl, 1- or 2-chloropropyl, hydroxyethyl and 1- or 2- hydroxypropyl.

Examples of suitable aryl groups R4 and R5 are: phenyl, diphenyl, 1-naphthyl and 2-naphthyl which may be substituted by from 1 to 3 halogen atoms, a phenyl group, from 1 to 3 alkyl groups each having from 1 to 4 carbon atoms, or a chloromethyl, fluoromethyl, carboxy, Ci~C4alkoxy or hydroxy group. Preference is given to substitution in the 3- and 4-positions on the phenyl ring, for example by fluorine, chlorine, C1-C4alkoxy or trifluoromethyl, or in the 4-position by hydroxy.

The cycloalkyl groups Rs may contain from 3 to 10, preferably from 3 to 6, carbon atoms in the ring. The rings may be substituted by alkyl groups having from 1 to 4 carbon atoms. There may be mentioned by way of example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclo5 pentyl and methylcyclohexyl.

The Ci-Cioalkyl groups mentioned in the definitions should be straight-chained or branched alkyl groups, such as those already mentioned for the alkyl groups above.

The hydroxy groups in R2, Y and W may be functionally modified, for example by etherification or esterification, it being possible for the free or modified hydroxy group in W to be in the a- or β-configuration; free hydroxy groups are preferred.

Suitable ether and acyl radicals are the radicals known to a person skilled in the art. Preference is given to readily removable ether radicals, such as, for example, a tetrahydropyranyl, tetrahydrofuranyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl or tribenzylsilyl radical.

Examples of suitable acyl radicals are acetyl, propionyl, butyryl and benzoyl.

Halogen in the definitions of R4, R5, E and Y is fluorine, chlorine, bromine or iodine.

The radicals Ci-Cioalkanoyl or Cj-CiOalkanesulphonyl for R6 correspond to the alkyl groups of the same length already mentioned, with the difference that they are bonded to a carboxy group or to a sulphonyl group. Preference is given to C1-C4alkanoyl and Ci-C4alkanesulphonyl.

Suitable for salt formation with the free acids (R4 = H) are inorganic and organic bases, such as those known to a person skilled in the art for the formation of physiologically tolerable salts. There may be mentioned by way of example: alkali metal hydroxides, such as sodium or potassium hydroxide, alkaline earth metal hydroxides, such as calcium hydroxide, ammonia, amines, such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, morpholine, tris(hydroxymethyl)methylamine, etc..

Preference is given to the compounds of formula I wherein R1 represents the group COOR4 or CONHR6, R2 represents hydrogen, hydroxy, optionally halosubstituted Ci-C4alkyl, C6-C12aryl or C7-C26aralkyl, R4 represents hydrogen, or optionally halo-substituted C7-Ci6aralkyl, C5-C6cycloalkyl or Ci-CiOalkyl, R6 represents C1-C7alkanoyl/ C6-Ci2arylsulphonyl or C!-C 7 alkanesulphonyl, p is from 0 to 4, and n and r are each independently of the other 0 or 1.

Preference is given especially to the compounds of formula I wherein R1 represents the group COOR4, R2 represents hydrogen, hydroxy, phenyl or phenylethyl, R4 represents hydrogen or methyl, R6 represents methanesulphonyl, p is from 0 to 4, and n and r are each independently of the other 0 or 1.

The compounds of formula I according to the Application can be prepared as described in detail below: Ο Ο (IV) b) above, D is optionally alkyl-substituted alkylene or CHR1 represents a -COOR4 ester, R8 is hydrogen or bromine, and W is -CH(OH)-.

B II Ri HaI-SO2-R3 (VII) or O=C=N-R3(VIII) Rl ΙΟ wherein R2, R3, X, Z and Hal have the meanings given above, A, W and E are direct bonds, D represents -(CH2)2-NH-SO2- or ^2) X and Η H R1 represents a -COOR4 ester. wherein R2, R3, X, Z and Hal have the meanings given above, A, W and E are direct bonds, H D represents - (CH2) 0-NH-SO2-, ^^χor ~, and 1 H R1 represents a -COOR4 ester. (0 wherein R2, R3, η, V, X, Z and Hal have the meanings given above, A, D and E are direct bonds, W represents -[(CH2)n-V]n-, and R1 is a -COOR4 ester. wherein R2, R3, η, V, W, X, Z and Hal have the meanings given above, A, D and E are direct bonds, W represents - [ (CH2) n-vl n/ and R1 represents a -C00R4 ester.

The compounds of formula I can be prepared according to claim 3 in accordance with the process options described above.

The reaction conditions for the process steps are as follows: a) II » III (Process A) The oxidation of compounds of formula II is carried out in accordance with known methods, such as, for example, by the method of Swern, Collins, or using pyridinium dichromate or chlorochromate, in solvents, such as dichloromethane, diethyl ether, tetrahydrofuran, benzene or toluene, at from -80*C to -50*C (Swern) or up to +30’C (in the case of the other oxidation reactions) within a period of from io minutes to 8 hours. b) III -» V (Process A) , c) , d) V -> I (Process A) The reaction of the compounds III with the phosphonates IV and the subsequent reduction or elimination of HBr are carried out analogously to the conditions mentioned in 20 DE-OS 2845770. e) II ·» VI (Process B) The reaction of the compounds of formula II to form compounds of formula VI is carried out as in Examples 38a to 38c which relate to that reaction. f) VI «* I (Process B) The reaction of the compounds of formula VI with the compounds of formula VII or VIII is carried out as in Example 38 which relates to that reaction. g) IX » I (Process C) The reaction of the compounds of formula IX to form compounds of formula I is carried out as described in Example I, with C-C multiple bonds contained in D previously being hydrogenated, where appropriate, in accordance with the methods known to a person skilled in the art. h) X * XI (Process D) The reaction of the compounds of formula X to form compounds of formula XI is carried out as described in Example 1, with C-C multiple bonds contained in D previously being hydrogenated, where appropriate, in accordance with the methods known to a person skilled in the art. i) XI * I (Process D) The reaction of the compounds of formula XI with compounds of formula XII to form compounds of formula I is carried out as described in Example 15. k) XIII * I (Process E) The reaction of the compounds of formula XIII to form compounds of formula I is carried out as described in Example 1, with C-C multiple bonds contained in D previously being hydrogenated, where appropriate, in accordance with the methods known to a person skilled in the art.

The functionally modified hydroxy groups R2, R3 and W are 25 freed in accordance with the methods known to a person skilled in the art. For example, the removal of ether protecting groups is carried out in an aqueous solution of an organic acid, such as, for example, acetic acid, propionic acid, citric acid, etc., or in an aqueous solution of an inorganic acid, such as, for example, hydrochloric acid, or, in the case of tetrahydropyranyl ethers, using pyridinium p-toluenesulphonate, preferably in alcohols as solvent or using anhydrous magnesium bromide, preferably in diethyl ether as solvent.

In order to improve the solubility, it is advantageous when using aqueous-acidic reaction conditions to add a watermiscible inert solvent. Examples of solvents that have proved suitable are alcohols, such as methanol and ethanol, and ethers, such as dimethoxyethane, dioxane and tetrahydrofuran, the use of tetrahydrofuran being preferred.

The removal of the silyl ether protecting groups is effected, for example, with tetrabutylammonium fluoride in accordance with the methods known to a person skilled in the art. Examples of suitable solvents are tetrahydrofuran, diethyl ether, dioxane, methylene chloride, etc.. The removal is preferably carried out at temperatures of from 20*C to 80*C.

The acyl groups and esters in COOR4 of the cyclopentene derivatives are hydrolysed in accordance with the methods known to a person skilled in the art, such as, for example, with basic catalysts such as, for example, with alkali metal or alkaline earth metal carbonates or hydroxides in an alcohol or an aqueous solution of an alcohol. Alcohols that may be mentioned are aliphatic alcohols, such as, for example, methanol, ethanol, butanol, etc., but preferably methanol. Alkali metal carbonates and hydroxides that may be mentioned are lithium, sodium and potassium salts. The lithium and potassium salts are preferred. Examples of suitable alkaline earth metal carbonates and hydroxides are calcium carbonate, calcium hydroxide and barium carbonate. The reaction is generally carried out at from -10*C to +70*C, but preferably at +25*C.

The introduction of the ester group CO2R4 for R1 and CO2R5 for Y, in which groups R4 and R5, respectively, represent an alkyl group having from 1 to 10 carbon atoms, is carried out in accordance with the methods known to a person skilled in the art. The carboxy compounds (R4 = H and R5 = H) are reacted, for example, with diazohydrocarbons in a manner known per se. The esterification with diazohydrocarbons is effected, for example, by mixing a solution of the diazohydrocarbon in an inert solvent, preferably in diethyl ether, with the carboxy compound dissolved in the same solvent or in a different, likewise inert, solvent, such as, for example, methylene chloride. When the reaction has ceased after from 1 to 60 minutes, the solvent is removed and the ester is purifed in customary manner. Diazoalkanes are either known or can be prepared in accordance with known methods [Org. Reactions, Vol. 8, pages 389-394 (1954)].

The introduction of the ester group CO2R4 for R1 and CO2R5 for Y, in which groups R4 and R5, respectively, represent a substituted or unsubstituted aryl group, is carried out in accordance with the methods known to a person skilled in the art. For example, the 1-carboxy compounds are reacted together with the corresponding arylhydroxy compounds with dicyclohexylcarbodiimide in the presence of a suitable base, such as, for example, pyridine, DMAP or triethylamine, in an inert solvent, such as, for example, methylene chloride, ethylene chloride, chloroform, ethyl acetate or tetrahydrofuran, but preferably with chloroform. The reaction is carried out at temperatures of from -30*C to +50*C, preferably at +10*C.

The cyclopentene derivatives of formula I wherein R4 and R5 represent a hydrogen atom can be converted into salts with suitable amounts of the corresponding inorganic bases, with neutralisation. For example, when the corresponding acids are dissolved in water containing stoichiometric amounts of the base and the water is evaporated off or a watermiscible solvent, for example an alcohol or acetone, is added, the solid inorganic salt is obtained.

The amine salts are prepared in customary manner. For that purpose the acid is dissolved in a suitable solvent, such as, for example, ethanol, acetone, diethyl ether or benzene, and from 1 to 5 equivalents of the amine in question are added to the solution. The salt generally precipitates in solid form or is isolated in customary manner after evaporating off the solvent.

The free hydroxy groups are functionally modified in accordance with the methods known to a person skilled in the art. In order to introduce the ether protecting groups, reaction is carried out, for example, with dihydropyran or methylvinyl ether in methylene chloride or chloroform using catalytic amounts of an acid condensation agent, such as, for example, p-toluenesulphonic acid. The enol ether in question is added in excess, preferably in an amount from 1.2 to 10 times the amount theoretically required. The reaction normally takes place at from -10*C to +30*C and is complete after from 2 to 45 minutes.

In order to introduce silyl ether protecting groups, reaction is carried out, for example, with tert-butyldiphenylchlorosilane or tert-butyl-dimethylchlorosilane in dimethylformamide using a base, such as, for example, imidazole. The silyl chloride in question is added in excess, preferably in an amount from 1.05 to 4 times the amount theoretically required. The reaction normally takes place at from 0*C to 30 *C and is complete after from 1 to 24 hours.

The acyl protecting groups are introduced by reacting a compound of formula I in a manner known per se with a carboxylic acid derivative, such as, for example, an acid chloride, acid anhydride, etc..

Cyclodextrin clathrates are obtained analogously to the procedure of WO 87/05294.

Liposomes are manufactured in accordance with the process described in Pharmazie in unserer Zeit 11. 98 (1982).

The invention relates also to any stereoisomeric forms.

Biological activity and rance of applications of the novel TXAp antagonists: The compounds of this invention are suitable for the treatment of disorders of the cardiovascular system, of the stomach, the pancreas, the liver and the kidneys. They have hypotensive and bronchodilatory activity. They are outstandingly suitable for inhibiting thrombocyte activation. The novel TXA2 antagonists of formula I are therefore valuable pharmaceutical active ingredients. In addition, the compounds are distinguished by higher selectivity, substantially longer effectiveness and greater stability compared with similar TXA2 antagonists.

The novel TXA2 antagonists have the properties typical of this class of compounds, such as, for example, reduction of peripheral arterial, coronary and pulmonary vascular resistance, reduction in pulmonary blood pressure, reduction in systemic blood pressure without simultaneous reduction in cardiac output and coronary blood flow, stimulation of renal blood flow and the blood flow of other peripheral organs, increase in cerebral blood flow, inhibition of thrombocyte activation and dissolution of thromboses, inhibition of bronchoconstriction, inhibition of gastric acid secretion, cytoprotection of the heart, gastric mucosa and intestinal mucosa and of the liver, cytoprotection in the pancreas and in the kidneys and anti-allergic properties. The novel TXA2 antagonists are therefore suitable principally for the treatment of stroke, the prophylaxis and treatment of coronary heart disease, for example coronary thrombosis, in the treatment of myocardial infarction, and peripheral arterial disorders, for prophylaxis and treatment in the case of other thromboembolic disorders and in arteriosclerosis, in the case of ischaemic attacks of the central nervous system and other circulatory disorders of the brain, such as, for example, migraine, in the treatment of hypertension and in the treatment of diseases accompanied by an increase in pulmonary vascular resistance, such as, for example, pulmonary hypertension, and in the treatment of shock, asthma and allergic rhinitis. They can also be used to inhibit labour pains and to treat toxaemia of pregnancy.

The novel TXA2 antagonists can also be used to improve organ function after transplant, for example in the case of kidney transplant, to prevent rejection reactions, in place of heparin or as an adjuvant in dialysis or haemofiltration and in the preservation of blood plasma reserves, for example blood platelet reserves.

The novel TXA2 antagonists have antimetastatic activity and antiproliferative properties. They are suitable principally for the treatment of neoplasia.

The novel TXA2 antagonists can be used in combination with, for example, carbacyclins, prostacyclin and its analogues, 7-oxo-prostacyclins, prostaglandins and the derivatives thereof, and 6-oxo-PGEi- and 6-oxo-9-fluoro-prostaglandin derivatives, with TXA2 synthetase inhibitors, with phosphodiesterase inhibitors, with antagonists and receptor antagonists of various thrombocyte stimulators (e.g. ADP, thrombin, collagen, PAF, adrenalin, serotonin, fibrinogen) , with calcium antagonists, with fibrinolytic agents and thrombolytic agents, e.g. t-PA, streptokinase, with heparin and other anticoagulants, with cyclooxygenase inhibitors, for example acetylsalicylic acid, with inhibitors of lipoxygenases and antagonists of lipoxygenase products, with vasodilators, such as, for example, nitro compounds, with antihypertensives, such as, for example, β-blockers, or with diuretics.

The dosage of the compounds is from 0.1 to 1000 mg/day, preferably from 0.1 to 500 mg/day, and may be administered to human patients also in several partial doses. The unit dose for the pharmaceutically acceptable carrier is from 0.1 to 100 mg. For parenteral administration sterile injectable aqueous or oily solutions are used. Suitable for oral administration are, for example, tablets, dragees or capsules.

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

The active ingredients according to the invention are intended for use in conjunction with the customary excipients known in galenical pharmacy, for example for the preparation of hypotensive agents.

The unit dose range for ampoules is from 0.1 to 100 mg, for tablets 0.1 to 100 mg.

Example 1: 7- [5 (S) - (4-Toluenesulphonylamino) -cyclopent-l-enyl] -5(Z)heptenoic acid methyl ester: mg (139 μπιοί) of the compound prepared in accordance with Example la are dissolved in 2.5 ml of anhydrous toluene. 56 μΐ of anhydrous pyridine are added, the mixture is cooled to -60 *C under an atmosphere of dry argon and 42 μΐ of diethylaminosulphur trifluoride are added. The mixture is allowed to warm to O’C in the course of 3.5 hours and the reaction is stopped by the addition of 1 ml of a saturated sodium hydrogen carbonate solution. The mixture is diluted with water and extraction is carried out several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on four analytical thin-layer plates. A mixture of n-hexane and acetone is used as eluant and diethyl ether is used as elution agent. 16 mg (40 μιηοΐ, %) of 7- [ (1R, 2S, 5R) -2- (4-toluenesulphonylamino) 5-f luorocyclopentyl] -5 (Z) -heptenoic acid methyl ester and 20 mg (53 μπιοί, 29 %) of the title compound are isolated, in each case in the form of a colourless oil.

IR (film): 3270, 3050, 3010, 2930, 2860, 1730, 1600, 1440, 1330, 1305, 1160, 1100, 950, 910, 815 and 670 cm’1.

Example la: 7- [ (1R, 2S, 5S) -2- (4-Toluenesulphonylamino) -5-hydroxy-cyclopentyl]-5(Z)-heptenoic acid methyl ester: mg of finely powdered potassium carbonate are added to a solution of 140 mg (280 μπιοί) of the compound prepared in accordance with Example lb in 1.5 ml of methanol and the mixture is heated at 70*C for 1 hour. When the mixture has cooled, it is acidified with saturated citric acid, diluted with water and extracted several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on two analytical thin-layer plates. A mixture of n-hexane and ethyl acetate is used as eluant and diethyl ether is used as elution agent. 96 mg (243 pmol, 87 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3270, 2940, 2870, 1735, 1600, 1450, 1330, 1270, 1160, 1110, 1090, 1025, 815 and 665 cm-1.

Example lb: 7- [ (1R, 2S, 5S) -2- (4-Toluenesulphonylamino) -5-benzoyloxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 1.52 ml of triethylamine and 483 mg of p-toluenesulphonic acid chloride are added to a solution of 340 mg (984 pmol) of the amine prepared in accordance with Example lc in 30 ml of anhydrous dichloromethane and the mixture is stirred for 1.5 hours at 23 *C under an atmosphere of dry argon. The mixture is poured into a semi-concentrated solution of sodium chloride and extraction is carried out several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on approximately 70 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 330 mg (660 pmol, 67 %) of the title compound are isolated in the form of a colourless oil.

IR (film) : 3270, 2940, 2870, 1730, 1710, 1600, 1450, 1330, 1270, 1160, 1110, 1090, 1025, 905, 815, 710 and 665 cm'1.

Example lc: 7- [ (IR, 2S,5S) -2-Amino-5-benzoyloxycyclopentyl] -5 (Z) -heptenoic acid methyl ester (A) and 7- [ (1R,2S,5S) -2-trifluoroacetamido-5-benzoyloxycyclopentyl]-5 (Z)-heptenoic acid methyl ester (B) : 1.47 ml of trifluoroacetic acid are added to the solution obtained in accordance with Example Id and the mixture is heated under reflux for 6 hours. The mixture is left to stand for 14 hours at 23 *C and then concentrated and the residue is purified by chromatography on approximately 250 ml of fine silica gel using a gradient system of dichloromethane and methanol. 2.0 g (5.79 mmol, 43 % based on starting material in Example le) of title compound A and 1.53 g (3.47 mmol, 26 % based on starting material in Example le) of title compound B are isolated.

IR (CHC13) for A: 3500-2600, 2950, 2870, 1710, 1670, 1450, 1275, 1190, 1140 and 835 cm*1.

IR (film) for B: 3320, 2950, 2870, 1740-1690, 1600, 1550, 1450, 1435, 1270, 1210, 1180, 1110, 1070, 1025 and 710 cm'1.

Example Id: 7-[(IR,2S,5S)-2-Azidocarbonyl-5-benzoyloxycyclopentyl]5(Z)-heptenoic acid methyl ester: The residue obtained in accordance with Example le is dissolved in 20 ml of dichloromethane, the solution is cooled to 3*C and 10 mg of tetrabutylammonium hydrogen sulphate and a solution of 1.04 g of sodium azide in 3.5 ml of water are added thereto. The mixture is stirred for 2.5 hours and diluted with dichloromethane. The organic phase is separated off and dried over freshly calcined magnesium sulphate. The solution obtained after filtration is reacted further immediately.

Example le: 7- [ (IR, 2S, 5S) -2-Chlorocarbonyl-5-benzoyloxycyclopentyl] 5(Z)-heptenoic acid methyl ester: With ice-cooling, 2.13 ml of freshly distilled thionyl chloride are added to a solution of 5.0 g (13.4 mmol) of the compound prepared in accordance with Example If in 133 ml of anhydrous dichloromethane-and the mixture is stirred for 20 hours at 23*C under an atmosphere of dry argon. The mixture is concentrated and the residue obtained is reacted further without being purified.

Example If: 7- [ (1R, 2S,5S) -2-Hydroxycarbonyl-5-benzoyloxycyclopentyl] 5(Z)-heptenoic acid methyl ester: A solution of 30.2 g (83.9 mmol) of the alcohol prepared in accordance with Example lg in 725 ml of acetone is cooled to -15*C, 44 ml of a standard solution of chromosulphuric acid (Jones reagent) are added and the mixture is stirred for 3 hours at -10’C. Excess oxidising agent is destroyed by the addition of 13 ml of isopropanol. The mixture is diluted with water and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 1 litre of coarse silica gel using a gradient system of n-hexane and ethyl acetate. 29.3 g (78.3 mmol, 93 %) of the title compound are isolated in the form of a colourless oil.

IR(film): 3600-2500, 3060, 2950, 2860, 1740-1690, 1600, 1580, 1450, 1435, 1360, 1310, 1270, 1170, 1110 1070, 1025 and 710 cm1.

Example lq: 7- [ (1R,2S,5S) -2-Hydroxymethyl-5-benzoyloxycyclopentyl] 5(Z)-heptenoic acid methyl ester: 155 ml of a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran are added to a solution of 57.9 g (96.7 mmol) of the compound prepared in accordance with Example lh in 124 ml of anhydrous tetrahydrofuran and the mixture is stirred for 17 hours at 23’C under an atmosphere of dry argon. Water is added and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of coarse silica gel using a gradient system of n-hexane and ethyl acetate. 30.2 g (83.8 mmol, 87 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3060, 2940, 2860, 1735, 1710, 1600, 1580, 1360, 1310, 1275, 1170, 1110, 1070, 1025 and 715 cm-1.

Example lh: 7- [ (1R,2S,5S) - 2- (tert-Butyldiphenylsilyloxymethyl-5-benzo 15 yloxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: A solution of 47.9 g (96.7 mmol) of the compound prepared in accordance with Example li in 212 ml of anhydrous pyridine is cooled to 5’C under an atmosphere of dry argon, 29 ml of benzoyl chloride are added in the course of minutes and the mixture is stirred for 1.5 hours at *C. The mixture is poured into 600 ml of ice-water and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with 2N hydrochloric acid, water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of fine silica gel using a gradient system of n-hexane and ethyl acetate. 57.9 g (96.7 mmol, 100 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3040, 3000, 2950, 2930, 2850, 1735, 1710, 1600, 1450, 1425, 1360, 1310, 1270, 1110, 820, 740 and 705 cm-1.

Example li; 7- [ (1R, 2S,5S) -2- (tert-Butyldiphenylsilyloxymethyl) 5-hydroxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 33.4 g of potassium carbonate and 41.2 g of methyl iodide are added to a solution of 154 g of the crude product prepared in accordance with Example lj in 150 ml of acetone and the mixture is heated at 80*C for 6 hours. The mixture is concentrated, taken up in 400 ml of dichloromethane, washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of coarse silica gel using a gradient system of n-hexane and ethyl acetate. 47.9 g (96.8 mmol, 88 % based on starting material in Example lj) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3070, 3040, 3000, 2940, 2920, 2850, 1735, 1585, 1460, 1425, 1240, 1165, 1110, 1005, 820, 740 and 700 cm-1.

Example li: 7- [(1R,2S,5S) -2- (tert-Butyldiphenylsilyloxymethyl)5-hydroxycyclopentyl] -5 (Z) -heptenoic acid: A total of 50 g of finely powdered potassium tert-butanol25 ate is added in portions in the course of one hour to an emulsion of 99.7 g of carboxybutyltriphenylphosphonium bromide in 256 ml of anhydrous tetrahydrofuran and 600 ml of anhydrous dimethyl sulphoxide. The mixture is stirred until a clear red solution is obtained and then, rapidly, a solution of 43.8 g (110 mmol) of the compound prepared in accordance with Example lk in 130 ml of anhydrous tetrahydrofuran is added dropwise thereto. The mixture is allowed to react for 2 hours at 23 *C under an atmosphere of dry argon and then poured into ice-water. The pH is adjusted to 4-5 by the addition of a saturated citric acid solution and extraction is carried out several times with dichloromethane. The extracts obtained are then washed with water and saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue that is obtained is reacted further without being purified.

Example lk: (IS,3RS,5R,6S)-3-Hydroxy-6-(tert-butyldiphenylsilyloxymethyl)-2-oxabicyclo[3.3.0] octane: A solution of 45.8 g (116 mmol) of the compound prepared in accordance with Example 11 in 1.4 1 of anhydrous toluene is cooled to -70*C under an atmosphere of dry argon. 202 ml of a 1.2M solution of diisobutylaluminium hydride in toluene is added dropwise thereto in the course of one hour and the mixture is then stirred for one hour. Excess reducing agent is destroyed by the addition of 13 ml of isopropanol. The mixture is allowed to warm to 0*C, 100 ml of water are added dropwise thereto and the mixture is stirred at 23*C until a fine-grained precipitate has formed. After filtering with suction, washing with dichloromethane and removing the solvent, 43.8 g (110 mmol, 95 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3070, 3050, 2940, 2850, 1590, 1465, 1425, 1390, 1360, 1260, 1110, 1010, 940, 820, 740 and 700 cm-1.

Example 11: (IS, 5R, 6S) -3-0XO-6- (tert-butyldiphenylsilyloxymethyl) 2-oxabicyclo[3.3.0]octane: 136 g of sodium iodide, 118 g of zinc dust and 79 ml of water are added to a solution of 67 g (119 mmol) of the tosylate prepared in accordance with Example lm in 1.3 1 of dimethoxyethane and the mixture is heated under reflux for 16 hours. When the mixture has cooled, undissolved residues are filtered off and the filtrate is concentrated to approximately 200 ml. Water is then added and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with 10 % sodium hydrogen sulphate solution, water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of coarse silica gel using a gradient system of n-hexane and ethyl acetate. 45.8 g (116 mmol, 98 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3050, 2950, 2930, 2850, 1775, 1590, 1470, 1425, 1165, 1110, 1005, 820, 740 and 705 cm-1.

Example lm: (IS, 5R, 6S, 7R) -3-0ΧΟ-6- (tert-butyldiphenylsilyloxymethyl) 7-toluenesulphonyloxy- 2-oxabicyclo (3.3.0] octane: 62.8 g of p-toluenesulphonic acid chloride are added to a solution of 67.3 g (164 mmol) of the alcohol prepared in accordance with Example In in 260 ml of anhydrous pyridine and the mixture is stirred for 27 hours at 50 *C under an atmosphere of dry argon. The mixture is concentrated, water is added and extraction is carried out several times with dichloromethane. The extracts obtained are washed with water and saturated sodium chloride solution and then dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of coarse silica gel using a gradient system of n-hexane and ethyl acetate. 67 g (119 mmol, 72 %) of the title compound are isolated in the form of a colourless oil.

IR (CHC13) : 3070, 3030, 2960, 2930, 2860, 1770, 1600, 1470, 1425, 1365, 1190, 1175, 1110, 1040, 980, 960, 895, 875, 820 and 700 cm1.

Example In: (IS,5R,6S,7R) -3-0XO-6- (tert-butyldiphenylsilyloxymethyl) 7-hydroxy-2-oxabicyclo[3.3.0]octane: 14.9 g of potassium carbonate are added to a solution of 129 g (251 mmol) of (IS,5R,6S,7R)-3-oxo-6-(tert-butyl diphenylsilyloxymethyl) -7-benzoyloxy-2-oxabicyclo[3.3.0]octane in 1 litre of methanol and the mixture is stirred for 3 hours at 23*C under an atmosphere of dry argon. Water is added, the mixture is neutralised by the careful addition of 2N hydrochloric acid and concentrated and extraction is carried out several times with dichloromethane. The extracts obtained are washed with water and saturated sodium chloride solution and then dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 2 litres of fine silica gel using a gradient system of n-hexane and ethyl acetate. 97 g (236 mmol, 94 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3070, 3050, 2940, 2960, 1770, 1590, 1430, 1240, 1170, 1115, 1075, 825, 745, 705, 615 and 510 cm-1.

Example 2: 7- [5 (S) - (4-Toluenesulphonylamino) -cyclopent-l-enyl] -5 (Z) heptenoic acid: 0.5 ml of a 5 % lithium hydroxide solution is added to a solution of 20 mg (58 μ mol) of the compound prepared in accordance with Example 1 in 1 ml of methanol and the mixture is stirred for 1.5 hours at 23*C. The mixture is acidified by the addition of saturated citric acid and diluted with water and extraction is carried out several times with dichloromethane. The extracts obtained are washed with water and saturated sodium chloride solution and then dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on an analytical thin-layer plate. A mixture of dichloromethane and methanol is used as eluant and a mixture of chloroform and isopropanol is used 5 as elution agent. 12 mg (34 pmol, 59 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3270, 3050, 3010, 2930, 2860, 1710, 1600, 1440, 1330, 1305, 1160, 1095, 950, 910, 815, 665, 575 and 550 cm-1.

Example 3 : 7- [5 (S) - (Benzenesulphonylamino) -cyclopent-l-enyl] -5 (Z) heptenoic acid methyl ester: mg (210 pmol) of the compound prepared in accordance with Example 3a are reacted analogously to Example 1 and 15 after working-up and purifying 23 mg (63 pmol, 30 %) of 7- [5- (S) - (benzenesulphonylamino) -cyclopent-l-enyl] 5 (Z)-heptenoic acid methyl ester and 26 mg (68 pmol, 32 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3270, 3050, 3010, 2930, 2860, 1730, 1450, 1330, 1160, 1095, 755, 720 and 690 cm’1.

Example 3a: 7- [ (1R,2S, 5S) -2-Benzenesulphonylamino-5-hydroxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 270 mg (556 pmol) of the compound prepared in accordance with Example 3b are reacted analogously to Example la and after working-up and purifying 212 mg (556 pmol, 100 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3260, 3060, 2930, 2850, 1725, 1445, 1320, 1265, 1160, 1090, 1020 and 735 cm-1. - 27 Example 3b: 7- [ (1R,2S,5S) -2-Benzenesulphonylamino-5-benzoyloxycyclopentyl]-5(Z)-heptenoic acid methyl ester: 250 mg (724 pmol) of the compound prepared in accordance with Example lc are reacted analogously to Example lb with benzenesulphonic acid chloride and after working-up and purifying 270 mg (556 pmol, 77 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3270, 3060, 3000, 2950, 2860, 1730, 1715, 1600, 1585, 1450, 1330, 1315, 1270, 1160, 1110, 990, 1025, 910, 755, 715 and 690 cm1.

Example 4: 7- [5 (S) - (Benzenesulphonylamino)-cyclopent-l-enyl]-5(Z)heptenoic acid: mg (63 pmol) of the compound prepared in accordance with Example 3 are hydrolysed analogously to Example 2 and after working-up and purifying 22 mg (63 pmol, 1 00 %) of the title compound are isolated in the form of a colourless oil. ^H-NMR (CDC13): 6 = 1.35 - 2.4 (m, 10H), 2 .45 - 2.55 (m 1H) , 2.75 - 2.9 (m, 1H), 4.25 (m, 1H), 4.9 (s, NH), 5.3 5.55 (m, 3H), 7.45 - 7.6 (m, 3H), 7.9 (m, 2H) .

Example 5: 7- [5 (S) - (4-Fluorobenzylsulphonylamino)-cyclopent-l-enyl]5 (Z)-heptenoic acid methyl ester: mg (210 pmol) of the compound prepared in accordance with Example 5a are reacted analogously to Example 1 and after working-up and purifying 26 mg (65 pmol, 31 %) of 7- [ (1R,2S,5R)-2-(4-fluorobenzenesulphonylamino)-5-fluorocyclopentyl]-5(Z)-heptenoic acid methyl ester and 25 mg (66 pmol, 31 %) of the title compound are isolated, in each case in the form of a colourless oil.

IR (film): 3270, 3050, 2930, 2860, 1730, 1600, 1440, 1330, 1225, 1160, 1100, 840, 735 and 670 cm'1.

Example 5a: 7- [ (IR,2S,5S)-2-(4-Fluorobenzenesulphonylamino)-5-hydroxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 240 mg (477 pmol) of the compound prepared in accordance with Example 5b are reacted analogously to Example lb and after working-up and purifying 175 mg (438 pmol, 92 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3310, 3060, 3020, 2940, 2860, 1730, 1610, 1595, 1490, 1440, 1325, 1250, 1160, 835, 790, 740 and 700 cm-1.

Example 5b: 7- [ (1R,2S,5S)-2-(4-Fluorobenzenesulphonylamino)-5-benzoyloxycyclopentyl]-5(Z)-heptenoic acid methyl ester: 250 mg (724 pmol) of the compound prepared in accordance with Example lc are reacted analogously to Example lb with 4-fluorobenzenesulphonic acid chloride and after working-up and purifying 243 mg (483 pmol, 67 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3270, 3060, 3000, 2950, 2870, 1730, 1710, 1590, 1570, 1490, 1450, 1335, 1270, 1165, 1150, 1090, 1025, 910, 715 and 670 cm-1.

Example 6: 7- [5 (S) - (4-Fluorobenzylsulphonylamino) -cyclopent-l-enyl] 5(Z)-heptenoic acid: mg (66 pmol) of the compound prepared in accordance with Example 5 are hydrolysed analogously to Example 2 and after working-up and purifying 22 mg (60 pmol, 91 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13) : δ = 1.35 - 2.4 (m, 10H), 2.45 - 2.55 (m, 1H), 2.8 - 2.9 (m, 1H), 4.25 (m, 1H), 4.98 (d, NH), 5.3 5.55 (m, 3H) , 7.2 (m, 2H) , 7.9 (m, 2H) .

Example 7: 7- [5 (S) - (Quinon-8-ylsulphonylamino) -cyclopent-l-enyl] 5(Z)-heptenoic acid methyl ester: mg (171 μ mol) of the compound prepared in accordance with Example 7a are reacted analogously to Example 1 and after working-up and purifying 19 mg (44 pmol, 25 %) of 7- [ (1R,2S,5R) -2-quinon-8-ylsulphonylamino) -5-fluorocyclopentyl]-5 (Z)-heptenoic acid methyl ester and 29 mg (70 pmol, 41 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3280, 3010, 2940, 2850, 1730, 1610, 1595, 1560, 1490, 1430, 1330, 1210, 1165, 1140, 1060, 835, 790 and 680 cm1.

Example 7a: 7- [ (1R,2S,5S) -2- (Quinon-8-ylsulphonylamino) -5-hydroxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 339 mg (632 pmol) of the compound prepared in accordance with Example 7b are reacted analogously to Example la and after working-up and purifying 259 mg (596 pmol, 94 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3280, 3060, 3000, 2940, 2860, 1730, 1665, 1610, 1595, 1565, 1490, 1435, 1325, 1215, 1165, 1145, 1090, 835 and 790 cm1.

Example 7b: 7- [ (IR, 2S, 5S) -2- (Quinon-8-ylsulphonylamino) -5-benzoyloxycyclopentyl]-5 (Z)-heptenoic acid methyl ester: 250 mg (724 pmol) of the compound prepared in accordance with Example lc are reacted analogously to Example lb with quinon-8-ylsulphonic acid chloride and after working-up and purifying 339 mg (632 pmol, 87 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3270, 3060, 2950, 2860, 1730, 1710, 1675, 1600, 1565, 1490, 1450, 1435, 1330, 1270, 1245, 1165, 1145, 1110, 1070, 1045, 1025, 900, 835, 790 and 715 cm’1.

Example 8: 7- [5 (S) - (Quinon-8-ylsulphonylamino) -cyclopent-l-enyl] 10 5(Z)-heptenoic acid: mg (70 pmol) of the compound prepared in accordance with Example 7 are hydrolysed analogously to Example 2 and after working-up and purifying 24 mg (61 pmol, 87 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3280, 3010, 2940, 2850, 1710, 1610, 1600, 1560, 1490, 1430, 1330, 1210, 1160, 1060, 835, 790 and 680 cm'1.

Example 9: 7- [5 (S) - (Benzenesulphonylamino) -cyclopent-l-enyl] -heptanoic acid methyl ester: 109 mg (284 pmol) of the compound prepared in accordance with Example 9a are reacted analogously to Example 1 and after working-up and purifying 34 mg (88 pmol, 31 %) of 7- [ (IR, 2S, 5R) -2- (benzenesulphonylamino) -5-fluorocyclo25 pentyl] -heptanoic acid methyl ester and 42 mg (115 pmol, %) of the title compound are isolated, each in the form of a colourless oil.

IR (film): 3270, 3060, 2930, 2850, 1730, 1455, 1325, 1160, 1090, 755, 720 and 690 cm1.

Example 9a: 7-[(lR,2Ss,5S)-2-(Benzenesulphonylamino)-5-hydroxycyclopentyl] -5 (Z) -heptanoic acid methyl ester: 132 mg (346 pmol) of the compound prepared in accordance with Example 3a are dissolved in 5 ml of ethyl acetate, mg of palladium on carbon (5 %) are added and the mixture is hydrogenated at 1 atm until the theoretically calculated amount of hydrogen has been taken up. The mixture is filtered, and then washed and concentrated. 109 mg (284 pmol, 82 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3260, 2930, 2850, 1725, 1445, 1320, 1265, 1160, 1095, 1020 and 735 cm’1.

Example 10: 7-[5(S)-Benzenesulphonylamino)-cyclopent-l-enyl]-heptanoic acid: mg (115 pmol) of the compound prepared in accordance with Example 9 are hydrolysed analogously to Example 2 and after working-up and purifying 37 mg (105 pmol, 92 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): 8 = 1.1 - 2.3 (m, 14H), 2.35 (t, 2H), 4.23 (m, 1H), 4.5 (d, NH), 5.48 (d, 1H), 7.45 - 7.6 (m, 3H) , 7.9 (m, 2H).

Example 11: 7- [5 (S) - (4-Fluorobenzylsulphonylamino) -cyclopent-l-enyl] heptanoic acid methyl ester: 120 mg (299 pmol) of the compound prepared in accordance with Example 11a are reacted analogously to Example 1 and after working-up and purifying 33 mg (82 pmol, 27 %) of 7-[(IR, 2S,5R)-2-(4-fluorobenzenesulphonylamino)-5-fluorocyclopentyl] -heptanoic acid methyl ester and 44 mg (115 pmol, 38 %) of the title compound are isolated, in each case in the form of a colourless oil.

IR (film): 3270, 3060, 2930, 2850, 1730, 1590, 1490, 1435, 1330, 1230, 1155, 1095, 840, 735 and 670 cm’1.

Example 11a: 7- [ (IR, 2S, 5S) -2- (4-Fluorobenzenesulphonylamino) -5-hydroxycyclopentyl]-5(Z)-heptanoic acid methyl ester: 141 mg (355 pmol) of the compound prepared in accordance with Example 5a are hydrogenated analogously to Example 9a and after working-up 120 mg (300 pmol, 84 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3270, 2930, 2850, 1730, 1660, 1600, 1445, 1320, 1260, 1160, 1095, 1020, 925, 840 and 820 cm’1.

Example 12: 7- [5 (S) - (4-Fluorobenzylsulphonylamino) -cyclopent-l-enyl] heptanoic acid: mg (115 μτηοΐ) of the compound prepared in accordance with Example 11 are hydrolysed analogously to Example 2 and afer working-up and purifying 38 mg (103 pmol, 89 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13) : δ = 1.18 (m, 14H) , 2.38 (t, 2H) , 4.23 (m, 1H) , 4.52 (d, NH) , 5.48 (d, 1H) , 7.2 (t, 2H) , 7.9 (m, 2H).

Example 13: 7- [5 (S) - (Quinon-8-ylsulphonylamino) -cyclopent-l-enyl) heptanoic acid methyl ester: mg (179 pmol) of the compound prepared in accordance with Example 13a are reacted analogously to Example 2 and after working-up and purifying 19 mg (43 pmol, 24 %) of 7- [ (IR, 2S, 5R) -2- (quinon-8-ylsulphonylamino) -5-f luorocyclo33 pentyl] -heptanoic acid methyl ester and 24 mg (57 pmol, %) of the title compound are isolated, in each case in the form of a colourless oil.

IR (film): 3280, 3040, 2930, 2850, 1730, 1610, 1595, 1560, 1490, 1430, 1330, 1165, 1145, 1065, 835, 790 and 680 cm-1.

Example 13a; 7-[(IR,2S,5S)-2-(Quinon-8-ylsulphonylamino)-5-hydroxycyclopentyl] -5 (Z) -heptanoic acid methyl ester; 149 mg (344 pmol) of the compound prepared in accordance with Example 7a are hydrogenated analogously to Example 9a and after working-up 142 mg (327 pmol, 95 %) of the title compound are isolated in the form of a colourless oil.

IR (film); 3600-3200, 3520, 3410, 3280, 2940, 2850, 1725, 1665, 1595, 1490, 1455, 1430, 1320, 1160, 1140, 1020, 890, 840, 790, 735 and 675 cm-1.

Example 14; 7- [5 (S) - (Quinon-8-ylsulphonylamino) -cyclopent-l-enyl] heptanoic acid; mg (177 pmol) of the compound prepared in accordance with Example 13 are hydrolysed analogously to Example 2 and after working-up and purifying 61 mg (152 pmol, 86 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13) : 8 = 0.98 - 2.2 (m, 14H), 2.32 (t, 2H), 4.3 (m, 1H), 5.43 (d, 1H), 6.14 (d, NH) , 7.56 (dd, 1H), 7.65 (t, 1H), 8.06 (dd, 1H), 8.29 (dd, 1H), 8.45 (dd, 1H) , 9.02 (dd, 1H).

Example 15; 7- [ (4RS,5S) -4-Phenyl-5-benzyloxymethylcyclopent-l-enyl] 5(E/Z)-heptenoic acid; 0.42 ml of a 50 % KOH solution, 265 pi of benzyl chloride and 4 mg of tetrabutylammonium hydrogen sulphate are added to 32 mg (102 pmol) of the compound prepared in accordance with Example 15a and the mixture is stirred intensively for 18 hours at 23 ’C. The mixture is poured into ice-water and extraction is carried out several times with dichloromethane. The organic phase is dried over magnesium sulphate and excess benzyl chloride is removed by chromatography on 4 analytical thin-layer plates. A mixture of n-hexane and ethyl acetate is used as eluant and chloroform is used as 10 elution agent. The residue obtained is hydrolysed analogously to Example 2 and after working-up and purifying 11 mg (28 pmol, 28 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3060, 3020, 2920, 2850, 1710, 1600, 15 1495, 1455, 1405, 1240, 1100, 1070, 1030, 755, 735 and 700 cm-1.

Example 15a: 7-[(4RS,5S)-4-Phenyl-5-hydroxymethylcyclopent-l-enyl]5(E/Z)-heptenoic acid: 1.59 ml of a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran are added to a solution of 365 mg (660 pmol) of the compound prepared in accordance with Example 15b in 7.8 ml of anhydrous tetrahydrofuran and the mixture is stirred for 3 hours at 23 *C under an atmosphere 25 of dry argon. Water is added and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 30 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 165 mg (524 pmol, 80 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3060, 3020, 2920, 2850, 1730, 1450, 1375, 1255, 1150, 965, 760 and 700 cm1.

Example 15b: 7-[(4RS,5S)-4-Phenyl-5-(tert-butyldiphenylsilyloxymethyl)cyclopent-l-enyl]-5(E/Z)-heptenoic acid methyl ester: 742 mg (1.30 mmol) of the compound prepared in accordance with Example 15c are reacted analogously to Example 1 and after working-up and purifying 294 mg (532 pmol, 41 %) of the title compound and 337 mg (588 pmol, 45 %) of 7- [ (IR,2S,3RS,5R) -2-(tert-butyldiphenylsilyloxymethyl)10 3-phenyl-5-fluorocyclopentyl]-5(E/Z)-heptenoic acid methyl ester are isolated in the form of a colourless oil.

IR (film): 3070, 3030, 2960, 2930, 2860, 1735, 1600, 1590, 1425, 1110, 820, 740 and 700 cm’1.

Example 15c: 7-[(IR,2S,3RS,5S)-2-(tert-Butyldiphenylsilyloxymethyl)3-phenyl-5-hydroxycyclopentyl]-5 (E/Z)-heptenoic acid methyl ester (A) and 7-[(IR,2S,3RS,5R)-2-(tert-butyldiphenylsilyloxymethyl)3-phenyl-5-hydroxycyclopentyl] -5 (E/Z) -heptenoic acid methyl ester (B): 1.97 g (3.47 mmol) of the compound prepared in accordance with Example 15d are reacted analogously to Example 15 and after working-up and purifying 742 mg (1.30 mmol, 37 %) of title compound A and 925 mg (1.62 mmol, 47 %) of title compound B are isolated, in each case in the form of a colourless oil.

IR (film) for A: 3600-3200, 3070, 3020, 2950, 2920, 2850, 1735, 1600 , 1585 , 1450, 1425 , 1110 , 820, 760, 740 and 700 cm-1. 30 IR (film) for B: 3600-3200, 3060, 3020, 2950, 2920, 2850, 1730, 1600, 1590, 1450, 1425, 1265, 1110, 1060, 820, 740 and 700 cm-1.

Example 15d: 7- [ (1R,2S,3RS) -2- (tert-Butyldiphenylsilyloxymethyl) 3-phenyl-5-oxocyclopentyl]-5 (E/Z)-heptenoic acid methyl ester: 500 mg of copper(II) acetate are added to a solution of 11.82 g (24.0 mmol) of the compound prepared in accordance with Example 15e in 120 ml of anhydrous tetrahydrofuran and the mixture is cooled to -78 *C under an atmosphere of dry argon. 3.04 ml of trimethylchlorosilane and then 12.8 ml of a 3M solution of phenylmagnesium bromide in diethyl ether are added thereto. After 45 minutes the mixture is poured into saturated ammonium chloride solution and extraction is carried out several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on approximately 200 ml of fine silica gel. A gradient system of n-hexane and ethyl acetate is used as eluant. 9.78 g (17.2 mmol, 72 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3030, 2950, 2930, 2850, 1735, 1600, 1465, 1450, 1425, 1110, 1055, 820, 780, 740 and 700 cm’1.

Example 15e: 7- [ (1R,2S) -2- (tert-Butyldiphenylsilyloxymethyl) -5-oxocyclopent-3-enyl]-5(E/Z)-heptenoic acid methyl ester: A solution of 5.84 g (11.5 mmol) of the compound prepared in accordance with Example 15f in 52 ml of anhydrous pyridine is cooled to 3*C under an atmosphere of dry argon. 2.17 ml of methanesulphonic acid chloride are added dropwise and the mixture is then stirred for 2 hours at 3*C.

Ice is added, the mixture is diluted with water and extraction is carried out several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on approximately 200 ml of fine silica gel. A gradient system of n-hexane and ethyl acetate is used as eluant. 4.93 g (10.0 mmol, 87 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3040, 2950, 2930, 2850, 1735, 1705, 1585, 1425, 1110, 820, 740 and 700 cm’1.

Example 15f: 7- [ (IR, 2S, 3R) -2- (tert-Butyldiphenylsilyloxymethyl) 3- (tetrahydropyran-2-yloxy) -5-oxocyclopentyl] -5 (E/Z) 10 heptenoic acid methyl ester: 11.9 g (20.0 mmol) of the compound prepared in accordance with Example 15g are reacted analogously to Example If and after working-up and purifying 9.39 g (15.8 mmol, 79 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3040, 2940, 2850, 1740, 1590, 1425, 1110, 1075, 1030, 970, 820, 740 and 700 cm-1.

Example 15q: 7- [ (1R,2S,3R,5S) -2- (tert-Butyldiphenylsilyloxymethyl) 20 3- (tetrahydropyran-2-yloxy) -5-hydroxycyclopentyl] -5 (E/Z) heptenoic acid methyl ester: 22.4 g (47.8 mmol) of (IS, 3RS, 5R, 6S, 7R)-7-(tetrahydropyran-2-yloxy) -6- (tert-butyldiphenylsilyloxymethyl) -2-oxabicyclo[3.3.0]octan-3-ol are reacted analogously to Example lj using KOH-containing potassium tert-butanolate. After working-up and esterifying with an ethereal solution of diazomethane and purifying by chromatography on approximately 1.3 litres of fine silica gel using a gradient system of n-hexane and ethyl acetate, 21.6 g (36.3 mmol, 76 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3070, 3040, 2940, 2850, 1730, 1595, 1425, 1110, 1075, 1025, 970, 820, 740 and 700 cm-1.

Example 16: 7- [ (4RS, 5S) -4-Phenyl-5- [2- (4-fluorophenoxy) -ethoxymethyl] cyclopent-l-enyl]-5(E/Z)-heptenoic acid: mg (95 pmol) of the compound prepared in accordance with Example 15a are reacted analogously to Example 15 using 2- bromo-(4-fluorophenoxy)-ethane and after working-up and purifying 11 mg (25 pmol, 26 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3050, 3020, 2920, 2860, 1710, 1600, 1505, 1455, 1250, 1210, 1130, 825, 755, 745 and 700 cm1.

Example 17: 7- [ (4RS, 5S) -4-Phenyl-5- (3-methylbenzyloxymethyl) -cyclopent-l-enyl] -5(E/Z)-heptenoic acid: 24 mg (76 pmol) of the compound prepared in accordance with Example 15a are reacted analogously to Example 15 using 3- methylbenzyl bromide and after working-up and purifying 20 mg (49 pmol, 65 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3030, 2920, 2850, 1705, 1605, 1495, 1455, 1360, 1240, 1160, 1110, 1090, 970, 780, 755 and 700 cm1.

Example 18: 7- [ (4RS,5S) -4-Phenyl-5- (4-cyanobenzyloxymethyl) -cyclopent25 l-enyl]-5(E/Z)-heptenoic acid: mg (80 pmol) of the compound prepared in accordance with Example 15a are reacted analogously to Example 15 using 4- cyanobenzyl bromide and after working-up and purifying mg (29 pmol, 36 %) of the title compound are isolated in the form of a colourless Oil.

IR (film): 3600-2400, 3050, 3020, 2930, 2850, 2230, 1705, 1600, 1490, 1455, 1435, 1360, 1290, 1240, 1150, 1110, 1090, 970, 795, 760, 700 and 690 cm-1.

Example 19: 7- [ (4RS,5S) -4-Phenyl-5- (3,5-bis-trifluoromethylbenzyloxymethyl)-cyclopent-l-enyl]-5(E/Z)-heptenoic acid: mg (83 pmol) of the compound prepared in accordance with Example 15a are reacted analogously to Example 15 using 3,5-bis(trifluoromethyl)benzyl bromide and after working-up and purifying 23 mg (44 pmol, 53 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3060, 3030, 2930, 2860, 1710, 1625, 1600, 1495, 1455, 1380, 1355, 1280, 1175, 1135, 970, 885, 845, 755, 700 and 680 cm1.

Example 20: 7-[(4RS,5S)-4-Phenyl-5-(1-naphthylmethoxymethyl)-cyclopent-l-enyl] -5(E/Z)-heptenoic acid: mg (76 pmol) of the compound prepared in accordance with Example 15a are reacted analogously to Example 15 using 1-bromomethylnaphthalene and after working-up and purifying 16 mg (36 pmol, 48 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3050, 3020, 2930, 2850, 1705, 1600, 1455, 1280, 1235, 1165, 1100, 800, 790, 775, 760 and 700 cm1.

Example 21: 7- [ (4RS, 5R) -4-Phenyl-5-benzyloxymethylcyclopent-l-enyl] 5(Z)-heptenoic acid: mg (137 pmol) of the compound prepared in accordance with Example 21a are reacted analogously to Example 15 and after working-up and purifying 18 mg (46 pmol, 34 %) of the title compound are isolated in the form of a colourless oil.

IR (film) : 3600-2400., 3090, 3060, 3030, 2930, 2860, 1710, 1600, 1495, 1455, 1410, 1360, 1240, 1205, 1100, 1075, 1025, 755, 740 and 700 cm-1.

Example 21a; 7- [ (4RS,5R) -4-Phenyl-5-hydroxymethylcyclopent-l-enyl] 5(Z)-heptenoic acid: 2.27 g (4.11 mmol) of 7-[(4RS,5R)-4-phenyl-5-(tert-butyldiphenylsilyl oxymethyl)-cyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester, which is prepared analogously to Examples 15b to I5g and lj to In from (IR,5S,6R,7S)-3-oxo-6-(tert-butyldiphenylsilyloxymethyl) -7-benzoyloxy-2-oxabicyclo[3.3.0]octane, are reacted analogously to Example 15a and after working-up and purifying 1.28 g (4.07 mmol, 99 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3060, 3030, 2920, 2850, 1710, 1605, 1455, 1405, 1240, 1110, 1070, 1030, 755, 735 and 700 cm'1.

Example 22: 7- [ (4RS, 5R) -4-Phenyl-5- [2- (4-f luorophenoxy) -ethoxymethyl] cyclopent-l-enyl] -5 (Z) -heptenoic acid: mg (137 pmol) of the compound prepared in accordance with Example 21a are reacted analogously to Example 15 using 2-bromo-(4-fluorophenoxy)-ethane and after working-up and purifying 15 mg (34 pmol, 25 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3050, 3030, 2930, 2870, 1710, 1600, 1505, 1455, 1250, 1210, 1130, 830, 760, 745 and 700 cm-1.

Example 23: 7- [ (4RS, SR) -4-Phenyl-5- (3-methylbenzyloxymethyl) -cyclopent-l-enyl] -5(Z)-heptenoic acid: mg (137 pmol) of the compound prepared in accordance with Example 21a are reacted analogously to Example 15 using 3-methylbenzyl bromide and after working-up and purifying 27 mg (67 pmol, 49 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3030, 2930, 2860, 1710, 1605, 1495, 1455, 1410, 1360, 1240, 1155, 1010, 985, 780, 760 and 700 cm-1.

Example 24: 7- [ (4RS, 5R) -4-Phenyl-5- (4-cyanobenzyloxymethyl) -cyclopentl-enyl]-5 (Z)-heptenoic acid: mg (137 pmol) of the compound prepared in accordance with Example 21a are reacted analogously to Example 15 using 4-cyanobenzyl bromide and after working-up and purifying 28 mg (67 pmol, 49 %) of the title compound are isolated in the form of a colourless oil.

IR (film) : 3600-2400, 3080, 3060, 3030, 2930, 2850, 2230, 1710, 1610, 1455, 1415, 1360, 1240, 1125, 1110, 820, 760 and 700 cm-1.

Example 25: 7- [ (4RS, 5R) -4-Phenyl-5- (3-cyanobenzyloxymethyl) -cyclopentl-enyl]-5 (Z)-heptenoic acid: mg (137 pmol) of the compound prepared in accordance with Example 21a are reacted analogously to Example 15 using 3 -cyanobenzyl bromide and after working-up and purifying 33 mg (79 pmol, 58 %) of the title compound are isolated in the form of a colourless oil.

IR (film) : 3600-2400, 3080, 3060, 3030, 2930, 2850, 2230, 1710, 1600, 1490, 1455, 1435, 1410, 1360, 1240, 1150, 1115, 1090, 795, 760, 700 and 690 cm'1.

Example 26: 7- [ (4RS,5R) -4-Phenyl-5- [ (3RS,4S) -3-hydroxy-4-methyl-non1 (E) -en-6-ynyl] -cyclopent-l-enyl] -5 (Z) -heptenoic acid methyl ester: A solution of 206 mg (476 pmol) of the compound prepared in accordance with Example 26a is dissolved in 6 ml of anhydrous methanol and cooled to -40*C under an atmosphere of dry argon. A total of 105 mg of sodium borohydride is added in portions thereto. The mixture is then allowed to react for 15 minutes and excess reducing agent is destroyed by the addition of 180 pi of acetic acid. Water is added and extraction is carried out several times with dichloromethane. The extracts obtained are washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 30 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 175 mg (403 pmol, 85 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3050, 3020, 2960, 2920, 2850, 1735, 1600, 1490, 1450, 1435, 1315, 1240, 1150, 1020, 970, 755 and 700 cm-1.

Example 26a: 7- [ (4RS, 5R) -4-Phenyl-5- [3-oxo-4S-methyl-non-l (E) -en-6-ynyl]-cyclopent-l-enyl]-5 (Z)-heptenoic acid methyl ester: A solution of 205 mg of dimethyl-(2-oxo-3S-methyloct-5-ynyl)-phosphonate in 1.13 ml of tetrahydrofuran are added 3Q dropwise at -10’C under an atmosphere of dry argon to a suspension of 36.5 mg of sodium hydride dispersion (55 %) in 1.4 ml of anhydrous tetrahydrofuran and the mixture is stirred for 15 minutes. A solution of 273 mg (748 pmol) of the aldehyde prepared in accordance with Example 26b in 1.68 ml of tetrahydrofuran is added dropwise and the mixture is stirred for 1.5 hours at 5*C. Acetic acid is added and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with dilute sodium hydrogen carbonate solution and dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on approximately 30 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 206 mg (476 pmol, %) of the title compound are isolated in the form of a colourless oil.

IR (film) : 3060, 3030, 2970, 2930, 1730, 1690, 1665, 1625, 1490, 1450, 1430, 1360, 1170, 1040, 980, 760 and 700 cm1.

Example 26b: 7-[(4RS,5R) -4-Phenyl-5-formylcyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester: A solution of 348 pi of dimethyl sulphoxide in 1.22 ml of dichloromethane is added dropwise to a solution of 190 pi of freshly distilled oxalyl chloride in 3.04 ml of anhydrous dichloromethane at -60*C under an atmosphere of dry argon. The mixture is allowed to react for 15 minutes and then a solution of 470 mg (1.50 mmol) of the alcohol prepared in accordance with Example 21a in 3 ml of dichloromethane is added. The reaction mixture is allowed to react for 3 hours, 596 pi of triethylamine are added, and the mixture is poured into ice-water and extracted several times with di chloromethane. The combined organic extracts are dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is reacted further without being purified.

Example 27: 7- [ (4RS,5R)-4-Phenyl-5- [ (3RS,4S)-3-hydroxy-4-methyl-non1(E)-en-6-ynyl]-cyclopent-l-enyl]-5(Z)-heptenoic acid: 175 mg (403 pmol) of the compound prepared in accordance with Example 26 are hydrolysed analogously to Example 2 and after working-up and purifying 143 mg (340 pmol, 84 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3030, 2960, 2930, 2860, 1710, 1600, 1460, 1290, 1270, 1070, 1010, 970, 760 and 700 cm'1.

Example 28: 7- [(4RS,5R)-4-Phenyl-5- [(3RS,4RS)-3-hydroxy-4-phenylpent1(E)-enyl]-cyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester: 279 mg (630 pmol) of the compound prepared in accordance with Example 28a are reacted analogously to Example 26 and after working-up and purifying 239 mg (537 pmol, 85 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3050, 3020, 2950, 2930, 2850, 1730, 1600, 1490, 1450, 1260, 1150, 1010, 970, 755, 740 and 700 cm-1.

Example 28a: 7-[(4RS,5R)-4-Phenyl-5- [ (4RS)-3-oxo-4-phenylpent-1(E)-enyl]-cyclopent-l-enyl]-5 (Z)-heptenoic acid methyl ester: 273 mg (748 pmol) of the compound prepared in accordance with Example 26b is reacted analogously to Example 26a using dimethyl (2-oxo-3-phenylbutyl)phosphonate and after working-up and purifying 279 mg (630 pmol, 84 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3060, 3020, 2950, 2930, 2850, 1730, 1710, 1690, 1615, 1490, 1450, 1260, 1160, 1070, 1025, 980, 755, 735 and 700 cm1.

Example 29: 7-[(4RS,5R)-4-Phenyl-5-[(3RS,4RS)-3-hydroxy-4-phenylpent5 1(E)-enyl]-cyclopent-l-enyl]-5(Z)-heptenoic acid: 239 mg (538 pmol) of the compound prepared in accordance with Example 28 are hydrolysed analogously to Example 2 and after working-up and purifying 175 mg (406 pmol, 76 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3080, 3060, 3030, 2960, 2930, 2860, 1710, 1670, 1600, 1500, 1450, 1240, 980, 760 and 700 cm-1.

Example 30: 7-[(4RS,5R)-4-Phenyl-5-[3(RS)-hydroxyoct-1(E)-enyl]-cyclo15 pent-l-enyl]-5(Z)-heptenoic acid methyl ester: 174 mg (426 pmol) of the compound prepared in accordance with Example 30a are reacted analogously to Example 26 and after working-up and purifying 173 mg (421 pmol, 99 %) of the title compound are isolated in the form of a colourless ’ oil.

IR (film): 3600-3200, 3030, 2920, 2850, 1735, 1455, 1260, 1150, 1025, 970, 740 and 700 cm’1.

Example 30a: 7-[(4RS,5R)-4-Phenyl-5-(3-oxooct-l(E)-enyl]-cyclopent-l-en25 yl]-5(Z)-heptenoic acid methyl ester: 245 mg (784 pmol) of the compound prepared in accordance with Example 26b are reacted analogously to Example 26a using dimethyl (2-oxoheptyl)phosphonate and after working-up and purifying 174 mg (426 pmol, 54 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3030, 2950, 2930, 2850, 1735, 1690, 1670, 1620, 1450, 1430, 1365, 1240, 1160, 1025, 860, 755 and 700 cm’1.

Example 31: 7-[(4RS,5R)-4-Phenyl-5-[3(RS)-hydroxyoct-1(E)-enyl]-cyclopent-l-enyl]-5(Z)-heptenoic acid: 173 mg (421 pmol) of the compound prepared in accordance with Example 30 are hydrolysed analogously to Example 2 and after working-up and purifying 100 mg (252 pmol, 60 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3060, 3030, 2940, 2860, 1710, 1605, 1455, 1410, 1240, 970, 760 and 700 cm*1.

Example 32: 7- [ (4S, 5R) -4-Hydroxy-5- [ (E/Z) -diphenylmethoxyiminomethyl] cyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester: 2 ml of a mixture of acetic acid, water and tetrahydro furan (65:35:10) are added to 46 mg (89 pmol) of the compound prepared in accordance with Example 32a and the mixture is stirred at 23*C for 18 hours. The mixture is concentrated, residual acetic acid is removed by repeated azeotropic distillation with toluene and the residue is purified by chromatography on approximately 10 ml of fine silica gel. mg (76 pmol, 86 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3060, 3030, 3010, 2930, 2860, 1735, 1600, 1495, 1455, 1240, 1080, 1030, 1020, 935, 740 and 700 cm-1. - 47 Example 32a: 7-[(IS,2R,3S,5S)-2-((E/Z)-Diphenylmethoxyiminomethyl]3- (tetrahydropyran-2-yloxy) -5-fluorocyclopentyl] -5 (Z) -heptenoic acid methyl ester (A) and 7- ((5R,4S)-5-[(E/Z)-diphenylmethoxyiminomethyl]-4-(tetrahydropyran-2-yloxy)-cyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester: 252 mg (471 pmol) of the compound prepared in accordance with Example 32b are reacted analogously to Example 1 and after working-up and purifying 72 mg (134 pmol, 28 %) of title compound A and 58 mg (112 pmol, 24 %) of title compound B are isolated, in each case in the form of a colourless oil.

IR (film): 3600-3200, 3060, 3030, 3010, 2940, 2870, 1730, 1600, 1455, 1245, 1020, 935, 870, 820, 745 and 700 cm’1.

Example 32b: 7-[(IS,2R,3S,5R)-2-[(E/Z)-Diphenylmethoxyiminomethyl]3-(tetrahydropyran-2-yloxy)-5-hydroxycyclopentyl]5(Z)-heptenoic acid methyl ester: 2θ An ethereal solution of diazomethane is added to a solution of 257 mg (493 pmol) of the compound prepared in accordance with Example 32c in 10 ml of dichloromethane and when the reaction is complete the mixture is concentrated. 262 mg (489 pmol, 99 %) of the title compound are isolated in the 25 form of a colourless oil.

IR (film): 3600-3200, 3070, 3030, 3010, 2950, 2870, 1740, 1455, 1440, 1350, 1200, 1130, 1080, 1025, 975, 910, 870, 815, 745 and 705 cm'1.

Example 32c: 7- [ (IS, 2R, 3S, 5R) -2- [ (E/Z) -Diphenylmethoxyiminomethyl] 3- (tetrahydropyran-2-yloxy) -5-hydroxycyclopentyl] 5(Z)-heptenoic acid: 569 mg (889 pmol) of the compound prepared in accordance with Example 3 2d are hydrolysed analogously to Example 2 and after working-up and purifying 399 mg (765 pmol, 86 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3070, 3030, 3010, 2940, 270, 1730, 1710, 1605, 1495, 1445, 1345, 1245, 1205, 1185, 1130, 1080, 1020, 975, 920, 870, 810, 745 and 705 cm-1.

Example 32d: 7- ((IS, 2R,3S, 5R) -2- [ (E/Z) -Diphenylmethoxyiminomethyl] 15 3- (tetrahydropyran-2-yloxy) -5-benzoyloxycyclopentyl] -5 (Z) heptenoic acid methyl ester: 120 pi of anhydrous pyridine and 176 mg of diphenylmethoxyamine are added to a colourless solution of 300 mg (654 pmol) of the compound prepared in accordance with Example 32e in 16 ml of anhydrous ethanol and the mixture is heated for 3.5 hours at 50*C under an atmosphere of dry argon. The mixture is concentrated and the residue is taken up in dichloromethane and washed with water and saturated sodium chloride solution. The residue obtained after drying over magnesium sulphate, filtration and concentration is purified by chromatography on approximately 50 ml of silica gel using an n-hexane/ethyl acetate mixture. 268 mg (453 pmol, 69 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3380, 3210, 3100, 3010, 2950, 2870, 1735, 1715, 1690, 1600, 1535, 1450, 1360, 1320, 1275, 1115, 1070, 1030, 970, 870, 815, 760, 715 and 695 cm'1.

Example 32e: 7-[(IS,2R,3S,5R)-2-Formyl-3-(tetrahydropyran-2-yloxy) 5-benzoyloxycyclopentyl]-5 (Z) -heptenoic acid methyl ester: 1.2 g (2.61 mmol) of the compound prepared in accordacne 5 with Example 32f are reacted analogously to Example 26b and after working-up 1.2 g (2.61 mmol, 100 %) of the title compound are isolated and are reacted further without being purified.

Example 32f: 7- [ (IS, 2R, 3S, 5R) -2-Hydroxymethyl-3- (tetrahydropyran-2-yloxy)-5-benzoyloxycyclopentyl]-5 (Z) -heptenoic acid methyl ester: 21.6 g (3.09 mmol) of the compound prepared in accordance with Example 32g are reacted analogously to Example lg and after working-up and purifying 1.2 g (2.61 mmol, 85 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3060, 3000, 2940, 2860, 1735, 1710, 1600, 1585, 1450, 1355, 1310, 1270, 1110, 1070, 1025, 865, 810 and 710 cm'1.

Example 32q: 7- [ (IS, 2R, 3S, 5R) -2- (tert-Butyldiphenylsilyloxymethyl) 3- (tetrahydropyran-2-yloxy) -5-benzoyloxycyclopentyl] 5(Z)-heptenoic acid methyl ester: 59.4 g (99.9 mmol) of 7-[(IS,2R,3S,5R)-2-(tert-butyldiphenylsilyloxymethyl) -3- (tetrahydropyran-2-yloxy) 5-hydroxycyclopentyl]-5 (Z)-heptenoic acid methyl ester are reacted analogously to Example lh and after working-up and purifying 62.5 g (89.4 mmol, 90 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3070, 3050, 3010, 2950, 2860, 1740, 1715, 1600, 1585, 1450, 1425, 1275, 1110, 1025, 970, 870, 825, 790, 710, 690, 610 and 500 cm'1.

Example 33: 7- [ (4S,5R) -4-Hydroxy-5- [ (E/Z) -diphenylmethoxyiminomethyl] cyclopent-l-enyl]-5(Z)-heptenoic acid: mg (58 pmol) of the compound prepared in accordance with Example 32 are hydrolysed analogously to Example 2 and after working-up and purifying 19.5 mg (46 pmol, 80 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3090, 3060, 3030, 3010, 2930, 2860, 1710, 1600, 1495, 1455, 1240, 1080, 1030, 1020, 935, 745 and 700 cm-1.

Example 34: 7- [ (4S, 5R) -4-Hydroxy-5- (3-methylbenzyloxymethyl) -cyclo15 pent-l-enyl]-5(Z)-heptenoic acid methyl ester: 212 mg (478 pmol) of compound B prepared in accordance with Example 34a are reacted analogously to Example 32 and after working-up and purifying 92 mg (257 pmol, 54 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3010, 2950, 2920, 2860, 1735, 1610, 1590, 1440, 1360, 1245, 1155, 1085, 1035, 780, 740 and 695 cm-1.

Example 34a: 7- [ (is, 2R,3S, 5S) -2- (3-Methylbenzyloxymethyl) -3- (tetrahydropyran-2-yloxy) -5-f luorocyclopentyl] -5 (Z) -heptenoic acid methyl ester (A) and 7-[ (5R, 4S)-5-(3-methylbenzyloxymethyl) -4- (tetrahydropyran-2-yloxy) -cyclopent-l-enyl] 5(Z)-heptenoic acid methyl ester (B): 800 mg (1.74 mmol) of the compound prepared in accordance with Example 34b are reacted analogously to Example 1 and after working-up and purifying 201 mg (436 pmol, 25 %) of title compond A and 212 mg (480 pmol, 28 %) of title compound B are isolated, in each case in the form of a colourless oil.

IR (film): 3600-3200, 3010, 2940, 2850, 1730, 1610, 1440, 1360, 1250, 1225, 1155, 1095, 870, 815, 780, 745 and 695 cm*1.

Example 34b: 7- [ (IS, 2R, 3S, 5R) -2- (3-Methylbenzyloxymethyl) -3- (tetrahydro10 pyran-2-yloxy) -5-hydroxycyclopentyl] -5 (Z) -heptenoic acid methyl ester: 1.23 g (2.75 mmol) of the compound prepared in accordance with Example 32f are reacted analogously to Example 15 and after working-up and purifying 1.18 g (2.56 mmol, 93 %) of 15 the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3300, 3010, 2940, 2860, 1740, 1610, 1595, 1440, 1355, 1250, 1200, 1155, 1115, 1075, 1020, 975, 905, 870, 815, 780, 745 and 695 cm*1. 2θ Example 3 5: - ((4S, 5R) -4-Hydroxy-5- (3-methylbenzyloxymethyl) -cyclopent-l-enyl]-5(Z)-heptenoic acid: mg (95 pmol) of the compound prepared in accordance with Example 34 are hydrolysed analogously to Example 2 and after working-up and purifying 17 mg (49 pmol, 52 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3010, 2930, 2860, 1710, 1610, 1590, 1455, 1405, 1355, 1240, 1155, 1080, 780, 745 and 695 cm*1.

Example 36; 7- [5R-(3-Methylbenzyloxymethyl)-cyclopent-l-enyl]5(Z)-heptenoic acid methyl ester: 89.5 mg of sodium iodide, 77 mg of zinc dust and 670 μΐ of water are added to a solution of 61 mg (115 pmol) of the tosylate prepared in accordance with Example 36a in 0.9 ml of dimethoxyethane and the mixture is heated for 3.5 hours under reflux. After cooling, undissolved residues are filtered off and the filtrate is diluted with diethyl ether. Water is added and extraction is carried out several times with diethyl ether. The combined organic extracts are washed with 10 % sodium hydrogen sulphate solution, water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 20 ml of silica gel using a gradient system of n-hexane and ethyl acetate. 32.9 mg (91 pmol, 79 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3010, 2950, 2860, 1740, 1610, 1590, 1440, 1360, 1245, 1220, 1160, 1105, 1090, 780, 745 and 695 cm’1.

Example 36a: 7- [ (4S, 5R) -4-Toluenesulphonyloxy-5- (3-methylbenzyloxymethyl)-cyclopent-l-enyl]-5 (Z)-heptenoic acid methyl ester: 122 mg of p-toluenesulphonic acid chloride are added to a solution of 58.3 mg (154 pmol) of the alcohol prepared in accordance with Example 34 in 1 ml of anhydrous pyridine and the mixture is stirred for 1.5 hours at 55*C under an atmosphere of dry argon. The mixture is concentrated, water is added and extraction is carried out several times with di chloromethane. The extracts obtained are washed with water and saturated sodium chloride solution and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 20 ml of silica gel using a gradient system of n-hexane and ethyl acetate. 61 mg (115 pmol, 74 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3010, 2950, 2860, 1735, 1600, 1440, 1360, 1190, 1175, 1095, 990, 885, 840, 815, 785, 695 and 665 cm-1.

Example 37: 7- [5R- (3-Methylbenzyloxymethyl) -cyclopent-l-enyl] -5(Z)heptenoic acid: mg (67 pmol) of the compound prepared in accordance with Example 36 are hydrolysed analogously to Example 2 and after working-up and purifying 21.6 mg (62 pmol, 93 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-2400, 3010, 2930, 2860, 1710, 1610, 1590, 1455, 1435, 1360, 1240, 1160, 1105, 1090, 955, 780, 745 and 695 cm-1.

Example 3 8: 6- [ (5S) - (2-Nitrophenylsulphonylaminomethyl) - cyclopentl-enyl]-4 (Z)-hexenoic acid methyl ester: 125 pi of triethylamine and 38 mg of 2-nitrobenzenesulphonic acid chloride are added to a solution of 55 mg (max. 125 pmol) of the amine prepared in accordance with Example 38a in 0.4 ml of anhydrous dichloromethane and the mixture is stirred for 0.5 hour at 23*C under an atmosphere of dry argon. The mixture is poured into a semi-concentrated solution of sodium chloride and extraction is carried out several times with dichloromethane. The combined organic extracts are dried over magnesium sulphate and the residue obtained after removal of the solvent is purified by chromatography on two analytical thin-layer plates. A mixture of n-hexane and ethyl acetate is used as eluant and trichloromethane is used as elution agent. 22 mg (54 pmol, %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.6 - 1.75 (m, 1H), 2 - 2.4 (m, 6H), 2.55 - 2.8 (m, 3H), 2.97 (dd, 1H), 3.2 - 3.3 (m, 1H) , 3.66 5 (a, 3H), 5.26 (s, 1H), 5.32 - 5.54 (m, 3H), 7.74 (m, 2H) , 7.87 (m, 1H), 8.13 (m, 1H) .

Example 38a: 6-[(5S)- (Aminomethyl)-cyclopent-l-enyl]-4 (Z)-hexenoic acid methyl ester: 495 mg of triphenylphosphine are added'to a solution of 392 mg (1.57 mmol) of the compound prepared in accordance with Example 38b in 13 ml of tetrahydrofuran and the mixture is stirred for 17 hours at 23*C under an atmosphere of dry argon. 2.5 ml water are then added and the mixture is heated at 80*C for 1 hour, concentrated, taken up in dichloromethane and dried over magnesium sulphate. The residue obtained after filtration and removal of the solvent is purified by filtration on approximately 100 ml of coarse silica gel using a gradient system of dichloro20 methane, methanol and triethylamine. 621 mg (max. 1.57 mmol) of amine, which still contains impurities, are isolated and are reacted further without additional purification.

Example 38b: 6-[ (5S) - (Azidomethyl)-cyclopent-l-enyl]-4 (Z)-hexenoic acid methyl ester: 502 mg of sodium azide are added to a solution of 523 mg (1.82 mmol) of the bromide prepared in accordance with Example 38c in 39 ml of dimethyl formamide and the mixture is heated for 2.5 hours at 60*C under an atmosphere of dry argon. The mixture is poured into ice-water and extraction is carried out several times with diethyl ether. The organic phase is dried over magnesium sulphate and the residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 70 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 392 mg (1.57 mmol, 86 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 2950, 2930, 2850, 2100, 1735, 1435, 1355, 1265 and 1160 cm1.

Example 38c: 6- [ (5S) - (Bromomethyl) -cyclopent-l-enyl] -4 (Z) -hexenoic acid methyl ester: 1.87 ml of collidine, 4.62 g of tetrabromomethane and 3.65 g of triphenylphosphine are added to a solution of 680 mg (2.78 mmol) of compound B prepared in accordance with Example 38d in 20 ml of acetonitrile and the mixture is stirred for 7 hours at 23 *C under an atmosphere of dry argon. The mixture is concentrated and the residue obtained is purified by chromatography on approximately 200 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 682 mg (2.37 mmol, 85 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 2950, 2850, 1735, 1440, 1245, 1215 and 1160 cm-1.

Example 38d: 6- [ (IR, 2S, 5R) -2-Hydroxymethyl-5-f luorocyclopentyl] -4 (Z) hexenoic acid methyl ester (A) and 6-[ (5S)-5-hydroxycyclopent-l-enyl]-4(Z)-hexenoic acid methyl ester (B) : 3.69 g of the mixture of compounds prepared in accordance with Example 38e are reacted analogously to Example lg and after working-up and purifying 943 mg (4.20 mmol, 40 %) of title compound B are isolated as the non-polar component and 758 mg (3.10 mmol, 30 %) of title compound A as the polar component, in each case in the form of a colourless oil.

IR (film) for A: 3200-3600, 3050, 2950, 2870, 1735, 1435, 1360, 1165, 1040, 945 and 875 cm'1.

IR (film) for B: 3200-3600, 3050, 2940, 2850, 1735, 1435, 1360, 1200, 1160 and 1025 cm'1.

Example 38e: 6-((1R,2S,5R)-2-tert-Butyldiphenylsilyloxymethyl-5-fluorocyclopentyl] -4(Z)-hexenoic acid methyl ester and 6-[(5S)-5-tert-butyldiphenylsilyloxymethyl)-cyclopentl-enyl] -4 (Z) -hexenoic acid methyl ester: .0 g (10.4 mmol) of the compound prepared in accordance with Example 38f are reacted analogously to Example 1 and after working-up and purifying 3.81 g of a mixture of the two title compounds are isolated in the form of a colourless oil.

Example 38f: 6- [ (1R,2S,5S) -2-tert-Butyldiphenylsilyloxymethyl-5-hydroxy cyclopentyl]-4(Z)-hexenoic acid methyl ester: 62.6 g (max. 58.3 mmol) of the compound prepared in accord ance with Example 38g are reacted analogously to Example 32b and after working-up and purifying 26.8 g (55.7 mmol, %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3600-3200, 3070, 3040, 2950, 2930, 2850, 1735, 1585, 1460, 1425, 1240, 1160, 1110, 1005, 820, 740 and 700 cm'1.

Example 38q: 6- [ (1R,2S,5S) -2-tert-Butyldiphenylsilyloxymethyl-5-hydroxy cyclopentyl]-4(Z)-hexenoic acid: 23.1 g (58.3 mmol) of the compound prepared in accordance with Example lk are reacted analogously to Example lj using carboxypropyltriphenylphosphonium bromide and after working-up 62.6 g of the title compound are isolated in the form of a crude product which is reacted further without being purified.

Example 39; 6-[(5S)-(2-Nitrophenylsulphonylaminomethyl)-cyclopentl-enyl] -4 (Z) -hexenoic acid: mg (54 pmol) of the compound prepared in accordance with 10 Example 38 are hydrolysed analogously to Example 2 and after working-up and purifying 18 mg (46 pmol, 85 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.55 - 1.68 (m, 1H), 1.9 - 2.4 (m, 7H), 15 2.5 - 2.8 (m, 3H), 2.92 (m, 1H) , 3.19 (m, 1H), 5.19 (dd, 1H) , 5.25 - 5.5 (m, 3H), 7.67 (m, 2H), 7.79 (m, 1H), 8.06 (m, 1H).

Example 40: 6- [ (5S) - (4-Fluorophenylsulphonylaminomethyl) -cyclopent20 l-enyl]-4(Z)-hexenoic acid methyl ester: mg (max. 125 pmol) of the compound prepared in accordance with Example 38a are reacted analogously to Example 38 using 4-fluorobenzenesulphonic acid chloride and after working-up and purifying 19 mg (50 pmol, 40 %) of the title compound are isolated in the form of a colourless oil.

XH-NMR (CDC13): δ = 1.63 - 1.75 (m, 1H), 1.95 - 2.4 (m, 7H) , 2.5 - 2.78 (m, 3H), 2.88 (m, 1H), 3.1 (m, 1H), 4.79 (dd, 1H), 5.32 - 5.5 (m, 3H), 7.19 (m, 2H), 7.89 (m, 2H).

Example 41: 6- [ (5S) - (4-Fluorophenylsulphonylaminomethyl) -cyclopent-lenyl] -4(Z)-hexenoic acid: mg (50 pmol) of the compound prepared in accordance with Example 40 are hydrolysed analogously to Example 2 and after working-up and purifying 17 mg (46 pmol, 93 %) of the title compound are isolated in the form of a colourless oil.

XH-NMR (CDC13) : δ = 1.5 - 1.65 (m, 1H) , 1.87 - 2.4 (m, 7H) , 2.45 - 2.72 (m, 3H) , 2.8 (m, 1H) , 3.02 (m, 1H) , 4.78 (dd, 1H), 5.3 - 5.44 (m, 3H), 7.12 (m, 2H) , 7.8 (m, 2H) .

Example 42: 6- [ (5S) - (Phenylsulphonylaminomethyl) -cyclopent-l-enyl] 4(Z)-hexenoic acid methyl ester: 55 mg (max. 125 pmol) of the compound prepared in accordance with Example 38a are reacted analogously to Example 38 using benzenesulphonic acid chloride and after working-up and purifying 19 mg (52 pmol, 42 %) of the title compound are isolated in the form of a colourless oil.

XH-NMR (CDCI3) : δ = 1.63 - 1.75 (m, 1H) , 1.95 - 2.4 (m, 6H), 2.48 - 2.75 (m, 3H), 2.88 (m, 1H) , 3.12 (m, 1H), 3.68 (s, 3H) , 4.69 (dd, 1H) , 5.32-5.5 (m, 3H) , 7.48 - 7.62 (m, 3H), 7.88 (m, 2H) .

Example 43: 6- ((5S) - (Phenylsulphonylaminomethyl) -cyclopent-l-enyl] 4(Z)-hexenoic acid: mg (52 pmol) of the compound prepared in accordance with Example 42 are hydrolysed analogously to Example 2 and after working-up and purifying 16 mg (46 pmol, 88 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDCI3) : δ = 1.52 - 1.64 (m, 1H) , 1.87 2.7 (m 9H), 2.8 (m, 1H), 3.02 (m, 1H), 4.72 (dd, 1H), 5.25 - 5.45 (m, 3H), 7.4 - 7.56 Example 44: - [ (5S)-(4-Methylphenylsulphonylaminomethyl)-cyclopent-15 enyl]-4(Z)-hexenoic acid methyl ester: mg (max. 125 pmol) of the compound prepared in accordance with Example 38a are reacted analogously to Example 38 using 4-toluenesulphonic acid chloride and after working-up and purifying 20 mg (53 pmol, 42 %) of the title compound 10 are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.66 - 1.79 (m, 1H), 2 - 2.45 (m, 6H), 2.49 - 2.8 (m, 3H), 2.91 (m, 1H), 3.12 (m, 1H), 3.68 (s, 3H) , 5.07 (dd, 1H) , 5.35 - 5.5 (m, 3H), 7.6 (d, 1H), 7.7 (dd, 1H), 7.98 (d, 1H) .

Example 45: 6- [ (5S)- (4-Methylphenylsulphonylaminomethyl)-cyclopent-lenyl]-4 (Z)-hexenoic acid: mg (53 pmol) of the compound prepared in accordance with Example 44 are hydrolysed analogously to Example 2 and 20 after working-up and purifying 18 mg (50 pmol, 93 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.5 - 1.63 (m, 1H), 1.86 - 2.4 (m, 10H), 2.45 - 2.7 (m, 3H), 2.76 (m, 1H), 3 (m, 1H), 3.67 (s, 3H) , 4.67 (dd, 1H), 5.27 - 5.42 (m, 3H), 7.22 (d, 2H), 7.68 (d, 2H).

Example 46: 6-[(5S)-(3,4-Dichlorophenylsulphonylaminomethyl)-cyclopent-l-enyl] -4 (Z) -hexenoic acid methyl ester: 55 mg (max. 125 pmol) of the compound prepared in accordance with Example 38a are reacted analogously to Example 38 using 3,4-dichlorobenzenesulphonic acid chloride and after working-up and purifying 21 mg (49 pmol, 39 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.65 - 1.78 (m, 1H), 2 - 2.45 (m, 7H), 2.48 - 2.82 (m, 3H), 2.92 (m, 1H), 3.12 (m, 1H), 5.08 (dd, 1H) , 5.35 - 5.5 (m, 3H) 7.6 (d, 1H), 7.7 (dd, 2H), 7.98 (d, 1H) .

Example 47: 6-[(5S) -(3,4-Dichlorophenylsulphonylaminomethyl)-cyclo10 pent-l-enyl]-4(Z)-hexenoic acid: mg (75 pmol) of the compound prepared in accordance with Example 46 are hydrolysed analogously to Example 2 and after working-up and purifying 15 mg (36 pmol, 48 %) of the title compound are isolated in the form of a colourless I5 oil. 1H-NMR (CDCI3): δ = 1.55 - 1.68 (m, 1H), 1.92 - 2.4 (m, 8H), 2.45 - 2.75 (m, 3H), 2.82 (m, 1H), 3.04 (m, 1H), 4.94 (dd, 1H), 5.3 - 5.45 (m, 3H), 7.53 (d, 1H), 7.62 (dd, 1H) , 7.9 (d, 1H).

Example 48: - [ (5S) - (4-Chlorophenylsulphonylaminomethyl) -cyclopent-lenyl]-4 (Z)-hexenoic acid methyl ester: mg (max. 125 pmol) of the compound prepared in accordance with Example 38a are reacted analogously to Example 38 using 4-chlorobenzenesulphonic acid chloride and after working-up and purifying 25 mg (63 pmol, 50 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDCI3): δ = 1.62 - 1.74 (m, 1H), 1.96 - 2.4 (m, 7H), 2.5 - 2.77 (m, 3H), 2.88 (m, 1H), 3.08 (m, 1H), 3.67 (s, 3H), 4.8 (dd, 1H), 5.35 - 5.5 (m, 3H) 7.49 (d, 2H) , 7.82 (d, 2H).

Example 49: 6- [(5S)- (4-Chlorophenylsulphonylaminomethyl) -cyclopent-lenyl]-4 (Z)-hexenoic acid: mg (63 pmol) of the compound prepared in accordance with ’ Example 48 are hydrolysed analogously to Example 2 and after working-up and purifying 18 mg (47 pmol, 74 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13) : 5 = 1.58 - 1.7 (m, 1H) , 1.95 - 2.45 (m, 10 7H) , 2.53 - 2.78 (m, 3H), 2.86 (m, 1H) , 3.08 (m, 1H), 4.84 (dd, 1H), 5.35 - 5.5 (m, 3H), 7.49 (d, 2H) , 7.8 (d, 2H) .

Example 50: 7- [(5S)-(2,4-Difluorophenylsulphonylaminomethyl)-cyclopent-l-enyl] -5 (Z) -heptenoic acid methyl ester: 143 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using 2,4-difluorobenzenesulphonic acid chloride and after working-up and purifying 12 mg (29 pmol, 12 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3200-3350, 3010, 2950, 2850, 1730, 1590, 1490, 1435, 1330, 1235, 1170, 1150, 1095, 840 and 670 cm’1.

Example 50a: 7-[(5S)-(Aminomethyl)-cyclopent-l-enyl]-5(Z)-heptenoic acid methyl ester: 969 mg of triphenylphosphine are added to a solution of 765 mg (3.07 mmol) of the compound prepared in accordance with Example 50b in 26 ml of tetrahydrofuran and the mixture is heated for 3.5 hours at 50*C under an atmosphere of dry argon. 3.3 ml of water are then added and the mixture is heated under reflux for 1 hour, concentrated, taken up in dichloromethane and dried over magnesium sulphate. After filtration and removal of the solvent 1.79 g (max. 3.07 mmol) of amine containing triphenylphosphine and triphenylphosphine oxide as impurities are isolated and reacted further without being purified.

Example 50b: 7- [ (5S) - (Azidomethyl) -cyclopent-l-enyl] -5 (Z) -heptenoic acid methyl ester: 853 mg of sodium azide are added to a solution of 933 mg (3.09 mmol) of the bromide prepared in accordance with Example 50c in 67 ml of dimethylformamide and the mixture is heated for 3 hours at 60*C under an atmosphere of dry argon. The mixture is poured into ice-water and extraction is carried out several times with diethyl ether. The organic phase is dried over magnesium sulphate and the residue obtained after filtration and removal of the solvent is purified by chromatography on approximately 200 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 765 mg (2.90 mmol, 94 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 2950, 2850, 2100, 1735, 1435, 1355, 1260 and 1160 cm'1.

Example 50c: 7- ((5S) - (Bromomethyl) -cyclopent-l-enyl] -5 (Z) -heptenoic acid methyl ester: 2.66 ml of collidine, 6.56 g of tetrabromomethane and 5.18 g of triphenylphosphine are added to a solution of 941 mg (3.95 mmol) of 7-[ (5S)-5-hydroxycyclopent-l-enyl] 5(Z)-heptenoic acid methyl ester, which is prepared analogously to Examples 38d to 38g and lj using carboxybutyltriphenylphosphonium bromide, in 29 ml of acetonitrile. The mixture is stirred for 6 hours at 23 *C under an atmosphere of dry argon and concentrated. The residue obtained is purified by chromatography on approximately 200 ml of fine silica gel using a gradient system of n-hexane and ethyl acetate. 933 mg (3.25 mmol, 82 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 2950, 2850, 1735, 1435, 1245, 1215 and 1160 cm1.

Example 51: 7- [ (5S) - (2,4-Difluorophenylsulphonylaminomethyl) -cyclopent-l-enyl] -5(Z)-heptenoic acid: mg (30 pmol) of the compound prepared in accordance with 10 Example 50 are hydrolysed analogously to Example 2 and after working-up and purifying 4 mg (10 pmol, 33 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13) : δ = 1.6 - 1.75 (m, 3H) , 1.95 - 2.4 (m, 8H) , 2.5 - 2.8 (m, 3H), 2.97 (m, 1H), 3.13 (m, 1H) , 5.03 (dd, 1H) , 5.37 - 5.54 (m, 3H), 6.93 - 7.05 (m, 2H) , 7.92 (m, 1H) .

Example 52 : 7- [ (5S) - (3,4-Dimethoxyphenylsulphonylaminomethyl) -cyclo2° pent-l-enyl]-5(Z)-heptenoic acid methyl ester: 144 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using 3,4-dimethoxybenzenesulphonic acid chloride and after working-up and purifying 14 mg (32 pmol, 13 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDCI3) : δ = 1.5 - 1.72 (m, 3H) , 1.85 - 2.5 (m, 8H) , 2.56 - 2.74 (m, 2H), 2.86 (m, 1H) , 2.98 (m, 1H, , 3.65 (s, 3H), 3.83 (s, 3H), 3.87 (s, 3H) , 4.8 (dd, 1H) , 5.28-5.45 (m, 3H), 6.86 (d, 1H), 7.29 (d, 1H) , 7.4 (dd, 1H) .

Example 53: 7- [ (5S) - (3,4-Dimethoxyphenylsulphonylaminomethyl) -cyclopent-l-enyl]-5(Z)-heptenoic acid: mg (34 pmol) of the compound prepared in accordance with Example 52 are hydrolysed analogously to Example 2 and after working-up and purifying 8 mg (19 pmol, 56 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.49 - 1.7 (m, 3H), 1.87 - 2.48 (m, •0 8H), 2.59 - 2.73 (m, 2H), 2.85 (m, 1H), 2.98 (m, 1H), 3.85 (s, 3H) , 3.88 (s, 3H) , 4.8 (dd, 1H), 5.28 - 5.45 (m, 3H), 6.87 (d, 1H), 7.3 (d, 1H), 7.42 (dd, 1H).

Example 54: 7-[(5S)-(4-Fluorophenylsulphonylaminomethyl)-cyclopent15 l-enyl]-5 (Z)-heptenoic acid methyl ester: 143 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using 4-fluorobenzenesulphonic acid chloride and after working-up and purifying 35 mg (88 pmol, 36 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3200-3400, 3010, 2940, 2850, 1730, 1590, 1490, 1435, 1330, 1235, 1175, 1150, 1090, 840 and 670 cm-1.

Example 55: 7- ((5S) - (4-Fluorophenylsulphonylaminomethyl) -cyclopent25 l-enyl]-5 (Z)-heptenoic acid: mg (73 pmol) of the compound prepared in accordance with Example 54 are hydrolysed analogously to Example 2 and after working-up and purifying 14 mg (37 pmol, 50 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13):6 = 1.5 - 1.7 (m, 3H), 1.85 - 2.52 (m, 11H), 2.55 - 2.7 (m, 2H), 2.85 (m, 1H), 3 (m, 1H), 5 (m, 1H), .25 - 5.45 (m, 3H), 7.12 (m, 2H), 7.82 (m, 2H) .

Example 56: 7- [ (5S) - (2-Nitrophenylsulphonylaminomethyl) - cyclopent-lenyl]-5 (Z)-heptenoic acid methyl ester: 143 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using 2-nitrobenzenesulphonic acid chloride and after working-up and purifying 32 mg (76 pmol, 31 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3200-3400, 3090, 3010, 2940, 2850, 1730, 1590, 1540, 1435, 1410, 1360, 1340, 1170, 850, 780, 740, 730 and 655 cm1.

Example 57: - [ (5S) - (2-Nitrophenylsulphonylaminomethyl) -cyclopent-lenyl]-5 (Z)-heptenoic acid: mg (76 pmol) of the compound prepared in accordance with Example 56 are hydrolysed analogously to Example 2 and after working-up and purifying 19 mg (47 pmol, 61 %) of the title compound are isolated in the form of a colourless oil.

XH-NMR (CDC13): 5 = 1.6 - 1.75 (m, 3H), 1.95 - 2.4 (m, 7H) , 2.53 - 2.83 (m, 3H), 2.99 (m, 1H), 3.24 (m, 1H), 5.26 (dd, 1H), 5.33 - 5.55 (m, 3H), 7.75 (m, 2H) , 7.87 (m, 1H), 8.12 (m, 1H) .

Example 58: 7- [ (5S) - (3,4-Dichlorophenylsulphonylaminomethyl) -cyclopentl-enyl]-5 (Z)-heptenoic acid methyl ester: 143 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using 3,4-dichlorobenzenesulphonic acid chloride and after working-up and purifying 34 mg (76 pmol, 31 %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3200-3350, 3010, 2940, 2850, 1730, 1450, 1370, 1335, 1160, 1030, 820 and 675 cm’1. > Example 59: 7- ((5S) - (3,4-Dichlorophenylsulphonylaminomethyl) -cyclopent-l-enyl)-5(Z)-heptenoic acid: mg (76 pmol) of the compound prepared in accordance with Example 58 are hydrolysed analogously to Example 2 and after working-up and purifying 19 mg (44 pmol, 58 %) of the title compound are isolated in the form of a colourless oil.

XH-NMR (CDC13) : δ = 1.5 - 1.72 (m, 3H) , 1.88 - 2.5 (m, 9H) , 2.58 - 2.73 (m, 2H), 2.88 (m, 1H) , 3.03 (m, 1H), 5.02 (dd, 15 1H), 5.27 - 5.45 (m, 3H) , 7.52 (d, 1H) , 7.63 (dd, 1H), 7.9 (d, 1H) .

Example 60: - [ (5S) - (Phenylsulphonylaminomethyl) -cyclopent-l-enyl] 5(Z)-heptenoic acid methyl ester: 143 mg (max. 246 pmol) of the compound prepared in accordance with Example 50a are reacted analogously to Example 38 using benzenesulphonic acid chloride and after working-up and purifying 31 mg (85 pmol, %) of the title compound are isolated in the form of a colourless oil.

IR (film): 3200-3350, 3010, 2940, 2850, 1730, 1445, 1325, 1160, 1090, 755, 720 and 690 cm-1.

Example 61: 7- [ (5S) - (Phenylsulphonylaminomethyl) -cyclopent-l-enyl] 5(Z)-heptenoic acid: mg (85 pmol) of the compound prepared in accordance with Example 60 are hydrolysed analogously to Example 2 and after working-up and purifying 20 mg (55 pmol, 65 %) of the title compound are isolated in the form of a colourless oil. 1H-NMR (CDC13): δ = 1.45 - 1.7 (m, 3H>, 1.85 - 2.5 (m, 8H) , 2.57 - 2.7 (m, 2H), 2.83 (m, 1H) , 3.01 (m, 1H), 4.83 (dd, 1H) , 5.26 - 5.45 (m, 3H) , 7.4 - 7.57 (m, 3H), 7.8 (m, 2H) .

Claims

1. Cyclopentene derivatives of the formula I (D. wherein R 1 can be or COOR 4 , wherein R 4 can represent hydrogen, or optionally halo-, phenyl-, C x -C 4 alkoxy- or di-(Ci-C 4 )alkylaminosubstituted Ci-Ci O alkyl, C3-C 10 cycloalkyl or C 7 -Ci 6 aralkyl, Y-substituted phenacyl or C6-C 12 aryl, or a 5- or 6-membered 10 heterocyclic radical having at least one N, 0 or S atom, or R 1 can be -CONHR 6 , in which R 6 represents hydrogen, Ci-C 10 alkyl, Ci-C 10 alkanoyl, C$-Ci 2 arylsulphonyl or C x -C xo alkanesulphonyl, X represents -(CH 2 ) p -, -CH 2 -O- or -CH 2 -S-, 15 Z and A, each independently of the other, represent a direct bond, (Z)-CH=CH-, (E)-CH=CH- or -CsC-, p is from 0 to 5, n and r, each independently of the other, are from 0 to 2, R 2 represents OR 5 or R 5 , 20 w represents a direct bond, a group -[(CH 2 ) n -V] q -, a group -(CH 2 )„-V-(CH 2 )q-V-, a free or functionally modified hydroxymethylene group or a free or functionally modified H 3 C OH group, it being possible for the hydroxy group in each case to be in the a- or β-configuration, q is 1 or 2, D represents a direct bond, a straight-chained, saturated alkylene group having from 1 to 5 carbon atoms, a branched, saturated alkylene group or a straight-chained or branched, unsaturated alkylene group having from 2 to 5 carbon atoms, each of which may optionally be substituted by fluorine atoms; or - (CH 2 ) n -NH-SO 2 -, » O. ,Κ,,ο · N Ν' Η Η H V o -(CH0 X χ n N N or H -( CH 2V N '* Η V Y H I N. -(CH,) X go,. n N N' 2 Η H Η H V represents an O or S atom, E represents a direct bond, -C=C- or -CH=CR 7 -, wherein R 7 can be hydrogen, Cx-Csalkyl, halogen or trifluoromethyl, AWDE together can be a direct bond, AW together can be a direct bond, DE together can be a direct bond, R 3 represents =x y 1 -(CH,) )i Y2 —(CH,) C 3 -C 10 cycloalkyl or optionally Y-substituted Ci-Cioalkyl, wherein R 3 can be (^Ηϊ) =. Y 1 Λ represents a direct bond, m is 1 or 2, Y2 , only if A or W Y 1 and Υ 2 are identical or different and represent Y, Y represents hydrogen, halogen, N 3 , CF 3 , OR 5 , NO 2 , NH 2 , CN, COOR 5 or Cx-Cioalkyl, R 5 can be hydrogen, or optionally halo-substituted Ci-C 10 alkyl, C 6 -C 12 aryl or C 7 -C xe aralkyl, and, when R 4 represents hydrogen, the salts thereof with physiologically tolerable bases, as well as α-, β- or T-cyclodextrin clathrates, and the compounds of the formula I encapsulated with liposomes.

2. Medicaments consisting of one or more compounds of claim 1 and customary excipients, carriers and additives.

3. Process for the preparation of cyclopentene derivatives of the formula I, characterised in that the hydroxy compound of the formula II wherein R l , R 2 , X and Z have the meanings given above and R 1 represents a -COOR 4 ester group, in which R 4 has the meaning given above with the exception of hydrogen, is reacted, after oxidation with oxalyl chloride/dimethyl sulphoxide, in the presence of sodium hydride or sodium hydride/bromine with a dimethyl phosphonate of the formula V in which D, E and R 3 have the meaning given above, is then reduced and, optionally, hydrogen bromide is removed or, after bromination, azide formation .and reduction, the intermediate amine of the formula VI is reacted with a compound of the formula Hal-SO 2 -R 3 (VII) or O=C=N-R 3 (VITI) , in which Hal and R 3 have the meanings given above, or a compound of the formula IX or X HO is fluorinated, optionally reacted with a compound of the formula Hal-R 3 (XII) , in which Hal and R 3 have the meanings given above, C-C multiple bonds are optionally hydrogenated and the esters obtained are hydrolysed, converted into 10 salts, converted into cyclodextrj» clathrates or encapsulated with liposomes.

4. A compound substantially as hereinbefore described reference to the Examples.

5. A medicament substantially as hereinbefore described reference to the Examples.

6. A process substantially as hereinbefore described reference to the Examples.