DE2305044A1 - PROSTAGLANDIN DERIVATIVES - Google Patents

Description

DR. JUR. DIPL-CHEM. WALTER BEII

ALFRED HOSPPENER

DR. JUR. DIfL-CHiM. H.-J. WOLFP

DR, JUR. HANS O'.ii. AX

623 FRANKFIiEf AM MAiN-HöCHST · * «JajY 1973

ADOQtU) RASSt 5d '

Our No. 18

G.D. Searle & Co. Skokie, 111., V.St.A,

Prostaglandin derivatives

The present invention relates to prostaglandin derivatives, in particular 15-deoxy and 11,15-bis-deoxy prostaglandin derivatives the general formula

) COOK

(D

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wherein X is a methylene radical, a hydroxymethylene radical or an alkanoyloxymethylene radical, in which the alkanoyl radical has 1 to 7 carbon atoms, R is a hydrogen atom or an alkyl radical having 1 to 7 carbon atoms, Z is a vinylene or ethynylene radical, m is an integer greater than 5 and less than 8 and η mean an integer greater than ⁷ · than 2 and less than 6 and the wavy line represents the alternative - oC - or ß-configuration "or the epimer mixture. · ■ _ ■ - · _

According to the invention, the alkanoyl radicals contain 1 to 7 carbon atoms and are for example formyl, acetyl and Propionyl radicals; the alkyl radicals contain 1 to 7 carbon atoms and are, for example, methyl, ethyl, propyl and isopropyl residues.

In a preferred process for the preparation of the new compounds according to the invention, v / earth is used as the starting material ■ Compounds of the general formula

(ID

used, in which m has the meaning given above, 'Y is a methylene radical, a hydroxymethylene radical, an ■ Alkanoyloxyraetliylenrest, in which the alkanoyl radical has 1 to 7 carbon atoms, or a tetrahydropyranyloxymethylene radical and R' is a hydrogen atom, an alkyl radical or a tetrahydropyranyl radical * These compounds are made by methods described by Bagli et al. in Tetrahedron Letters, Ηβ5 (1966) and Heslinga et al. in rets. -Trav. Chim », 87, 1 ^ 21 (1968).

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The compounds according to the invention are prepared by that the compounds described above with an alkenyl copper, a trialkinyl aluminum or a Trialkiny.lborverbindungen be brought into contact. ■ These connections can be made through the following general formulas

CH (CH ₂ ) _n CH = CH-Cu

(CH ₂ ) _n C = CJ ₃ Al.

/ ₃ (CH ₂ ) _n C = C £ 7 ' ₃ B

represent, in which η has the meaning given above »

The trans-1-alkenyl copper compounds are made by adding from copper-I-iodide to the appropriate trans-1-alkenyl magnesium chloride prepared in a suitable solvent such as tetrahydrofuran. The trans-1-Alkeny! Magnesium chloride are produced by using mercury-II-chloride activated magnesium with trans-1-alkenylmercury-II-chloride is brought into contact, which is produced by first contacting the 1-alkynes with B. catechol borane and this product is then treated with mercury-II chloride.

The cis-1-alkenyl copper compounds are derived from the cis-1-alkenyl bromides produced by treating them one after the other with lithium and copper-i-iodide. The procedure for the preparation of the cis-1-Alkeny! bromide was from G.B. Bachman in J. Amer. Chem. Soc, 55, ^ 279 (1933) described.

The trialkinylaluminum compounds are made by the appropriate 1-alkyne with butyllithium and then treated with aluminum trichloride; the trialkinyl boron compounds are made in the same way except that boron trichloride, boron tribromide, boron trifluoride or boron trifluoride etherate is used. the

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Reactions are generally carried out in an appropriate manner Solvents such as ethyl ether, tetrahydrofuran or toluene carried out. The copper, boron and aluminum compounds are generally used in situ.

The trans-1-hexenylqueekilver (II) chloride is typically prepared by mixing 1-hexyne with catechol borane and then in contact with mercury (II) chloride is brought. The trans-l-hexenylmercury-II-chloride is then added to a suspension of magnesium powder and tetrahydrofuran. The trans-1-hexeny! magnesium chloride obtained is not isolated, but treated with copper I-iodide, with trans-1-hexenyl copper as an intermediate which is used in situ and with tetrahydropyran-2-yl-5-oxocyclopent-1-enheptanoate is treated, wherein the 2- (l-hexenyl) -5-axocyclopentanheptanoic acid according to the invention is obtained.

The preparation of the 2-alkynylcyclopentanalkanecarboxylic acid derivatives is carried out, for example, by treating 1-octyne with butyllithium and then adding aluminum _{tri t} chloride, trioctynylaluminum being obtained which is used in situ and which is obtained with methyl 3-hydroxy-5-oxocyclopent-1-enheptanoate is implemented, the inventive. Methyl 3-hydroxy-2- (l-oc.tinyl) -5-oxocyclopentane heptanoate was obtained.

The epimeric mixtures prepared by the methods described above are separated by conventional chromatographic methods. For example, the epimers of methyl 3-hydroxy-2- (1-oct.inyl) -5-oxocyclopentane hemp canate are separated by columnar chromatography on silica gel using 5 % ethyl acetate in benzene as the eluent. The reactants can also be dissolved before they are alkenylated or alkynylated to prepare the compounds according to the invention.

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The new products according to the invention are considered pharmaceutical Medium suitable. They have, for example, an anti-ulcer effect, which is shown below Trial was tested:

The antiulcerogenic activity of the compounds according to the invention can be seen from the results of a standard test in which their ability to inhibit ulcer formation is tested, which according to Shay et "al., Gasteroenterology, Vol. 5, p. A3 (19 ^ 5) in rats nourished and subjected to pyloric ligation In this test, male Charles River rats weighing 200-500 g and which had not been nourished for 72 hours prior to ligation were used of the ligature, the prescribed dose of the compound dissolved or suspended in 1.0 ml of hydrochloric acid having a pH of 2.0 was administered intragastrically to each animal of a group of 6 animals The same manner and at the same time the acid alone was administered served as control animals. Exactly 19 hours later, the stomachs of the surviving animals were excised and magnified five times investigates. The number of occurrences in the non-secretory portion of each stomach ulcers vmrden depending on the size in ^l \ groups classified and counted (<2 mm, 2-4 mm, 4-8 mm and> 8 mm); Each rat received a rating z, which is the weighted mean of the logarithms of the number of ulcers in the individual groups, divided according to size, which is determined by a formula which is determined almost optimally by discriminant function analysis and is as follows:

ζ = 20.00 log (N ₁ + 1) + 0.22 log (N ₂ + 1) + 16.76 log (N ₇ + 1) + 6.11 log (N ₁ , + 1)

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where IL ·. .. KL means the number of ulcers found in the groups divided according to increasing size. Since long-term studies in about 400 animals showed that the average value for ζ in control animals is 96.2 with a normal deviation per group of 6 animals of 18.97, a decrease in the average value of ζ for a given test group is in relation to control animals tested simultaneously by 37 »5 ^: or more significant (P = 0.05); a compound which causes such a drop is considered to be antiulcerogenic. -

The following examples serve to illustrate the invention. The temperatures are given in degrees Celsius (° C) and the amounts of material are given in parts by weight, unless parts by volume are given. The ratio between parts by weight and parts by volume is the same as that between grams and milliliters. The IR maxima were determined in chloroform solution and are given in cm. The NMR spectra were determined using a 100 megahertz machine with tetramethylsilane terminated as an internal reference and are reported in Hertz. The values for the specific rotation relate to the D line, of sodium, with methanol being used as the solvent at room temperature. The measurements for optical rotational dispersion. were performed using a wavelength measured in millimicrons (mx).

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example 1

A solution of 200 parts by volume of 1 M borane in tetrahydrofuran, the was stirred at 0 ° C under an atmosphere of nitrogen content, was added dropwise within 30 minutes, while stirring, 22 parts of catechol in ^ h parts of tetrahydrofuran. This solution was stirred at room temperature for 1 hour. Then 16 parts of 1-hexyne were added and the solution was refluxed for 2 hours. The reaction mixture was cooled to 0 ° C. and treated with 5 ^ parts of mercury (II) chloride. The resulting mixture was stirred at 0 ° C for 1 hour, after which it was allowed to warm to room temperature. After standing at room temperature for 16 hours, the mixture was poured into a 3: 1 mixture of water and acetone and the resulting white precipitate was collected and washed with water. The precipitate was then dissolved in boiling hexane, and the solution was filtered while it was hot and cooled to 0 ° C melted.

Example 2

Using an equivalent amount of 1-octyne in the process of Example 1 was. trans-1-octenylmercury-II chloride obtained that melted at about 104-105 ° C.

Example 3

1.0 part of 3-Hydroχy-5-oxocyclopent-l-enheptanoic acid, which is in Methanol was dissolved, a 5% ethereal diazomethane solution was added dropwise until a slight excess of diazomethane was present. This excess was found when the solution was a

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exhibited a steady yellow color. The solution was then evaporated to dryness under a nitrogen atmosphere, methyl ~ 3-hydroxy-5-oxocyclopent-1-enheptanoate obtained which melted at about 49-51 ° C.

Example 4

A mixture of 0.240 parts of methyl 3 (RS) -hydroxy-5-oxocyclopent-1-enheptanoate, 0.200 parts of 2 (S) -aminooxyisocaproic acid and 4 parts of methanol was treated with 0.5 part of pyridine. The mixture was left to stand for about 16 hours at room temperature and then poured into 45 parts of ethyl acetate and 20 parts by volume of 0.5 η hydrochloric acid. The ethyl acetate layer was separated, washed with water and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was chromatographed on silica gel using 1% ethyl acetate in chloroform as the eluant, yielding successive fractions of methyl-3 (R) -hydroxy-5Z * ^ l-carboxyisoamyl) oxyimino7cyclopent-l- enheptanoate with a melting point of about 62-63 C and methyl ~ 3 (S) -hydroxy-5 - / "(l-carboxyisoamyl) oxyiminQ_7cyclopent-1-enheptanoate with a melting point of 45-48 ° C were obtained.

Each of the above oximes was 1.5 parts Ammonium acetate, 1 part acetic acid, 10 parts water, 27 parts tetrahydrofuran and 3.0 parts by volume of one aqueous 20% txtan trichloride solution mixed and approx Stirred at 60 ° C. for 16 hours under a nitrogen atmosphere. Each mixture was then diluted with ether and mixed with water. The ether layer was separated and treated with a 2% aqueous sodium bicarbonate solution and water and dried over anhydrous sodium sulfate. »The solvent was reduced under reduced Pressure removed, with methyl 3 <R) -hydroxy-5-oxocy <: lopent-1-enheptanoate with a specific rotation of 4-16.8 ° or methyl ~ 3 (S) -hydroxy-5-oxocyclopent-l-en-

309832/1174

heptanoate with a specific rotation of -17.2 °.

Example 5

A suspension of 1.6 parts of magnesium powder and 27th parts of tetrahydrofuran, distilled from .einer ethylmagnesium bromide solution, was treated with 1 part of mercury (II) chloride. After the mixture was stirred for 15 minutes, 5> 1 parts of trans-1-hexenylmercuric chloride was added and this mixture was stirred at room temperature for about 16 hours. The excess magnesium was decanted off from the excess magnesium and then stirred and cooled to -60 ° C. in an isopropanol / dry ice bath. Then 3.0 parts of copper I-iodide were added in one portion, and the mixture was allowed to warm to -30 ° C. and kept at this temperature for 10 minutes. The mixture was then cooled to -60 ° C. and 1.47 parts of tetrahydropyran-2-yl-5-oxocyclopent-1-enheptahoate dissolved in tetrahydrofuran were added dropwise to the reaction mixture. This mixture was stirred for 30 minutes and then poured into a mixture of 140 parts of ethyl ether and 100 parts by volume of aqueous 0.5 η hydrochloric acid. The ether layer was separated, washed with water and dried over anhydrous sodium sulfate. The solvent was then removed under reduced pressure and the remaining material was contained 1 η aqueous hydrochloric acid in HO parts acetone containing 10 parts by volume of dissolved. This mixture was allowed to stand at room temperature for one hour, after which it was diluted with water and extracted with ether. The ether extract was washed with water, dried over anhydrous sodium sulfate and the solvent was stripped off. The residue was chromatographed on silica gel using ethyl acetate and benzene as the eluent, the racemic 2β- (1-hexenyl) -5 ~ oxo-6C-cyclopentane

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heptanoic acid was obtained as a yellow oil. This compound showed absorption maxima in the IR spectrum at around 1715 and 1739 cm " ¹ .

Example 6

When using an equivalent amount of trans-1-octenyl mercury TI chloride In the procedures of Example 5, the racemic 2β- (1-octenyl) -5-oxo-loc-cycldpentane- heptanoic acid obtained as a yellow oil. This compound showed absorption maxima in the IR spectrum at around 1715 and 1739 cm

Example 7

When using an equivalent amount. Methyl 3-hydroxy-5-oxoeyclopent-1-enheptanoate In the procedure of Example 5, the racemic methyl-2β- (1-ljexenyl) -3oC-hydroxy-5-0x0-1 oC-cyclopentane heptanoate, the racemic methyl-2c? C- (l-hexenyl) -3c? C. -hydroxy-S-oxo-1ß-cyclopentane heptanoate and the racemic methyl 2ß- (1-hexenyl) -3 <? <- hydroxy-5-oxo-1ß-cyclopentane heptanoate obtained as yellow oils. These compounds showed an absorption maximum in the IR spectrum at around 1744 era ".

Example 8

When using equivalent amounts of ¹ · trans-1-octenylmercuric chloride and methyl 3-hydroxy ~ 5-oxocyclopent-1-enheptanoate in the procedure of Example 5, the racemic methyl-2: £ -i l-oetenyl} - 3 <7 ^ -hydroxy ^ -bxo-lß-cyclopentane heptanoate, which is characterized by MMR peaks, in deuterochloroform, at about 559 (multiplet) and 430 (complex) Hertz, the racemic methyl 2ß- (l-octenyl) - 3 *? ^ - hydrQxy-5-oxö-li> C-cyclopentanheptanoate, which is characterized by NMR peaks, in deuterochloroformj at about 567 (multiplet), 530 (doublet) and 403 (complex) Hertz,

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230504A

ii - '

and the racemic methyl 2β- {1-octenyl) -3'- ⁱ ^ - hydroxy-5-oxo-1ß-cyclopentane heptanoate, which is characterized by an IR absorption maximum at about 17 ^ 8 cm. These compounds were all in the form of yellow oils.

Example 9

In the procedure of Example 5, equivalent amounts were used Methyl 3- (tetrahydropyran-2-yloxy) -5-oxocyclopent-1-enheptanoate and trans-1-octenyl mercury H-chloride used. Before the chromatography, however, the tetrahydropyranyl ether was cleaved by the residue, which remained after stripping off the solvent, in 5 parts by volume of a 19-10: 6 mixture of acetic acid, Water and tetrahydrofuran was dissolved and the mixture was heated to 60 ° C for 10 minutes. Subsequently was the mixture cooled and diluted with water and ether. The ethereal layer was separated, washed with water and dried over anhydrous sodium sulfate, .- and the solvent was stripped off. The column chromatography on silica gel using ethyl acetate

Racemic xn benzene as the eluxant gave rexnes / methyl 2ß- (1-octenyl) -3oC-hydroxy-5-oxo-1 ^ -cyclopentane heptanoate as a yellow oil; this product is identical to the second product of example 8.

Example 10

Using equivalent amounts of tetrahydropyran-2-yl-3 ~ (tetrahydropyran-2 ~ 3 ^ 1oxy) -5-oxocyclopcnt ~ 1-enheptanoate and trans-1-octenylmercuric chloride (II) in the procedure of Example 5 and treating the residue before chromatography in the V / eise as described in Example 9, the racemic 2ß- (l-octenyl) -3t ^ -hydroxy-5-oxo-loC-cyclopentanheptanoic acid was prepared, which at about 3 ^ -3! U ⁰ C melted.

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- 1 ? - "

Example 11 -

A maintained at -3O ⁰ C solution of 0.800 parts of 1-octyne in 7.1 parts of ethyl ether was treated with 2.6 volume parts of a 2.28 M solution in hexane von'Butyllithium. -This mixture was stirred at room temperature for 1 hour and then cooled to -60 ° C. 0.267 part of aluminum trichloride was added, and after the solution had been stirred for two hours at room temperature, 0.240 part of methyl 3-hydroxy-5-oxocyclopent-1-enheptanoate dissolved in ether was added in one portion. The mixture was stirred for 2 hours at room temperature and then poured into a mixture of 70 parts of ethyl ether and 50 parts by volume of 0.5 η aqueous hydrochloric acid. The ether layer was separated, washed with water and dried over anhydrous sodium sulfate. After the solvent had been removed, the remaining material was chromatographed on silica gel, and after elution with 5 % ethyl acetate in benzene, the racemic methyl- "; 2 <2C_ (i-octynyl) -3"! 7C-hydroxy-5-oxo -lß-cyclopentanheptanoate with a melting point of about 32 ° C and the racemic methyl-2 ot- (loctinyl) -30C-hydroxy-5-οχο-Ιοί. -cyclopentanheptanoat mil; a melting point of about 41-42 ° C.

Example 12

When using an equivalent amount of 1-hexyne in the Procedure of Example 11 were the racemic methyl

hydroxy-5-oxo ~ lß-cyelopentane heptanoate,

—1 by an IR absorption maximum at about 17 ^ 8 cm and the racemic methyl ~ 2o £ - (1-hexynyl) 3 /> C-hydroxy-5-oxo-loC-cyclopentane heptanoate, which is produced by a IR absorption maximum is marked at about 1746 cm, obtain*

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Example 13

When using an equivalent amount of tetrahydropyran-2-yl-5-oxocyclopent-1-enoctanoate In the procedure of Example 5, the racemic 2ß- (l-hexenyl) -5-oxo-

I oC-cyclopentanoctanoic acid obtained by IR absorption maxima marked at around 1715 and 17 * 10 cm.

Example Ik '

When using an equivalent amount of methyl 3-hydroxy-5-oxocyclopent-1-enoctanoate in the procedure of the example

II were the racemic methyl 2 ° £ - (1-octynyl) ~ 3oC-hydroxy-5-oxo-1ß-cyclopentanoctanoate, which is characterized by an IR absorption maximum at about 17 ^ 5 cm, and the racemic methyl-2 < : £ - (l-octinyl) -3oC-hydroxy-5-oxo - loC-cyclopentanoctanoate, which is characterized by an IR absorption maximum at about Π ^ι \ ~ $ cm obtained.

Example 15

When using an equivalent amount of ethyl 3-hydroxy-5-oxocyclopent-1-enheptanoate in the procedure of Example 11 were the racemic Xthyl-2c ^ * (l-octinyl) -3c ^ -hydroxy-5-oxo-lß-cyclopentane heptanoate, that by an IR absorption maximum is marked at about 17 ^ 8 cm, and that racemic ethyl-2 oC- (l-octinyl) ~ 3oC-hydroxy-5-oxo-l <? C - cyclopentane heptanoate, which is characterized by an IR absorption maximum at about 17 ^ 6 cm.

Example 16

A solution, cooled to -60 ° C., of 0.800 parts of 1-octyne in 7.1 parts of ethyl ether was treated with 2.6 parts by volume of a 2.3 M solution of butyllithium in hexane and stirred for 30 minutes at room temperature. The reaction mixture was then cooled to -60 ° C. with 2.17 parts by volume of an O ₄ 81 m solution of boron trichloride in toluene

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230504A

treated and stirred at a temperature of -2O ° C to -10 ° C for 20 minutes. 0.2 * 10 parts of methyl 3-hydroxy-5-oxocyclopent-1-enheptanoate dissolved in ether were added in one portion, and the resulting equipment was stirred at a temperature of -20.degree. C. to -10.degree. C. for 20 minutes . The mixture was allowed to slowly warm to 0 C and was kept at this temperature for 1 hour. Then it was in a mixture of 70 parts of ethyl ether un _; d poured 50 parts by volume of aqueous 0.5 η hydrochloric acid. The ether layer was separated, washed with water and dried over anhydrous sodium sulfate. After the solvent had been stripped off, the remaining material was chromatographed on a silica gel column, the racemic methyl 2oC- (1-octynyl) -3oC-hydroxy-5-oxo after elution with 5% ethyl acetate in benzene -lßcyclopentanheptanoat, which by an IR absorption maximum

- 1
at 'about 17 ^ 8 cm, the racemic methyl 2ß- (1-octynyl) -3 o ^ -hydroxy-5 ~ oxoMgyclopentariheptanoat, which by NMR peaks, in deuterochloroform, at about 456 (doublet), 316 (Doublet) and 266 (multiplet) Hertz, and the racemic methyl 2o £ - (1-octynyl) -3 oC-hydroxy-5-oxo-1 <? C-cyclopentane heptanoate, which is characterized by an IR absorption maximum at marked about 1746 cm.

Example 17

When using an equivalent amount of methyl 3-acetoxy-5-oxocyclopent-1-enheptanoate in the procedure of Example 5, the racemic methyl 3 - ^ - acetoxy-2ß- (1-hexonyl) -5-0x0-1 oC-cyclopentane heptanoate obtained by IR absorption maxima at around 1250 and 17 ^ 5 cm is.

Example 18

When using an equivalent amount of ethyl ~ 3 ~ ^af 2ctoxy-S-oxocyclopent-1-önheptanoat in the method of Example IC "

** YYT

om

3098 3 2/1 1 7 Λ

were then rasenische methyl 2oC- (l-octinyl) -3 ° C-aeetoxy-5-oxo-lß-cyclopentane heptanoate, the racemic methyl 2ß- (1-octynyl) -3 /? C ~ acetoxy-5-oxo-1 ''> C-cyclopentane heptanoate and the racemic methyl-2 <X _- (l-octinyl) ~ 3 <? £> acetoxy- -5-oxo-lcjC-cycloDentanheutanoat obtained. These connections 43 cm

Example 19

When using an equivalent amount of ethyl 3-propionyloxy-5-oxocyclopent-1-enheptanoate In the procedure of Example 16, the racemic methyl 2oC- (1-octynyl) -3 A-propionyloxy-5-oxo ~ lß-cyclopentane heptanoate, Racemic ethyl 2ß- (1-octynyl) -3-X-propionyloxy-5-oxo-1 ^ -cyclopentane heptanoate and racemic ethyl 2OC- (1-octynyl) -3 oC-propionyloxy-5-oxo-1 cC-cyclopentane heptanoate obtain. These compounds showed IR absorption maxima at about 1249 and 1746 cm ".,,

Example 20

When using an equivalent amount of methyl 1-5-oxocyclopent-1-enheptanoate in the procedure of Example 11, the racemic methyl was ~ 2β- (1-octynyl) -5-OXO-IoC-cyclopentane heptanoate which showed an IR absorption maximum at about 1745 cm.

Example 21

0.489 parts of ice-1-hexenyl bromide were added under nitrogen atmosphere dissolved in 5 parts of ether, and then the solution was cooled to -10 ° C and 0.042 parts treated with finely divided lithium. After completion of the reaction, the solution was cooled to -40 ° C and added 0.570 parts Copper-I-iodide added. The solution was 10 minutes at -30 ° C and then cooled to -60 ° C. Afterward 0.294 parts of tetrahydropyran-2-yl dissolved in ether

g "change g" most important input ·
Received on ... Λ ./. · .....- .. J. -vi

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S-oxocyclopent-l-enheptanoate added dropwise, and da.s reaction mixture was stirred at -60 ° C. for 30 minutes. The product obtained in the manner described in Example 5 was raceric 2β- (1-hexenyl) -5-oxo-loC -cyclopentanheptanoic acid obtained the IR Ab sorptiönsmaxiina at about 1714 and 17 ^ 2 ·

-1
cm showed.

Example 22

When using equivalent amounts of methyl 3 (S) -hydroxy-5-oxocyclopent-1-enheptanoate and methyl 3 (R) -hydroxy-5 * "oxocyclopent-1-enheptanoate in the procedure of Example 5 were the corresponding optically active methyl 2- (l-hexenyl) 3 (S) -hydroxy-5-oxocyclopentane heptanoate, which has an optical Rotary dispersion absorption of +0.9 at X = 315 mu

Max /

and methyl 2- (1-hexenyl) r3 (R) -hydroxy-5-oxocyclopentane heptanoate, which has a rotational dispersion optical absorption of -0.85 at J ^ -315 niu

max / "- <

up, received.

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Claims (17)

230504A Claims Il. j compounds of the general formula J COOR
d πι wherein X is a methylene radical, an Ilydroxymethylenerest or oxy
an Alkanoy lernet hy lenre st, vrorin the alkanoyl radical contains 1 to carbon atoms, R a hydrogen atom or an alkyl radical with 1 to 7 carbon atoms, Z a vinylene or ethynylene radical, m an integer greater than 5 and less than 8 and η an integer greater than 2 and less than 6 mean and the wavy line represents the alternative of the Oi or β configuration or the mixture of epimers. " 2. Compounds according to claim 1 of the general formula (CH ₂ ) COOR OR » 309832/1 174 wherein R 'represents a hydrogen atom or an alkanoyl residue 1 to 7 carbon atoms, R, Z, m and η have the meanings given in claim 1 and the Wavy lines the alternative to the oC or ß configuration -or represent the epimeric. 3. Compounds according to claim 1 of the general formula (CH ₂ ) _m COOR wherein R, Z, - m and η are those given in claim 1 Have meanings and the wavy line the alternative, the oC - or ß-configuration or the epimeric mixture represents. 4. Compounds according to claim 1 of the general formula COOR C SC (CH ₀ ) -CH-. Wherein R has the meaning given in claim 1 and R ¹ denotes a hydrogen atom or an alkanoyl radical having 1 to 7 carbon atoms, and the wavy lines 309832/1 MU the alternative '. represent the c £ - or ß-configuration or the mixture of epimers. 5- Compounds according to claim 1 of the general formula - (CH ₂ ) gC00R CH ₃ wherein R has the meaning given in claim 1, 6. Compounds according to claim 1 of the general formula s (CH ₂ ) _ß C00R = C (CH wherein R has the meaning given in claim 1. 7. Compounds according to claim 1 of the general formula (CH ₂ ) g COOR ₀ ), .CH 2 5 309832/117 4 wherein R has the meaning given in claim 1 and R 'is a hydrogen or an alkanoyl radical with 1 to Means 7 carbon atoms, and the wavy lines the alternative ^; ' the oC or ß configuration or • represent the mixture of epimers. 8. Compounds according to claim 1 of the general formula - (CH ₂ ) g COOR CH ₂ ) _r CH wherein R has the meaning given in claim 1, 9. Compounds according to claim 1 of the general formula COOR wherein R has the meaning given in claim 1. 10. Racemic methyl 2 ^ - <1 ~ hexenyl5-5oC-hydroxy-5-glycolß-cyclopentane heptanoate. 11. Racemic methyl 2Λ - (1-octenyl ) ~ 3oC -hydroxy -5-oxolß-cyclopentane heptanoate. 303632/1174 12. Racemic ethyl 2ß- (1-octenyl) -3 oC-hydroxy-5-oxo-1c ^ -cyclopentane heptanoate. 13. Racemic, 2ß- (1-hexenyl) -5-oxo-loC-cyclopentane-.heptanoic acid. I ¹ I. Racemic 2ß- (1-cetenyl) -5-oxo-10C-cyclopentanheptanoic acid. 15. Racemic methyl-2ß ~ (1-octynyl) -3oC-hydroxy-13-oxo-1 OC-cyclopentane heptanoate. 16. Racemic methyl 2oC- (1-octynyl) -30C-hydroxy-5-oxo-1cC-cyclopentane heptanoate. 17. Racemic methyl 2oC- (l-octynyl) -3oC-hydroxy-5-oxolß-cyclopentane heptanoate. For: G.D. Searle / S Co. Skokie, I1L. , V.St.A. (Dr H.JiWolff) Lawyer 309832/1