# Patent

## Title
Hypocholesterolemic fermentation products and process of preparation

## Abstract

This disclosure describes novel 16-aryloxy-17,18,19,20-tetranorprostanoic acids and derivatives thereof useful as bronchodilators and as hypotensive and contraceptive agents.

## Background
This invention relates to novel 16-aryloxy-17,18,19,20-tetranorprostanoic acids, their derivatives and intermediates for preparing same. More specifically the novel compounds of this invention can be represented by the following two general formulae wherein A has the same absolute configuration as is found in the naturally-occurring mammallian prostaglandins, and all the racemates, racemic mixtures and diasteromeric mixtures thereof. ##STR1## wherein R.sub.1 is hydroxy or an alkoxy group having from one to twelve carbon atoms; R.sub.2 is a phenyl, benzyl, naphthyl, or 5,6,7,8-tetrahydronaphthyl group optionally substituted with one or two of the following groups: halogen, lower alkyl, lower alkoxy, or trifluoromethyl radicals; n is an integer having the value 2 to 4, inclusive; Y is a divalent radical selected from the group consisting of ##STR2## X is a divalent radical selected from the group consisting of ##STR3## C.sub.5 -C.sub.6 is ethylene or cis-vinylene; C.sub.13 -C.sub.14 is ethylene or trans-vinylene; with the proviso that when C.sub.5 -C.sub.6 is cis-vinylene then C.sub.13 -C.sub.14 is trans-vinylene.

When X is ##STR4## it represents the 15.alpha.-hydroxy derivative, and the 15.beta.-hydroxy derivatives when it is ##STR5##

Suitable lower alkyl and lower alkoxy groups contemplated by the present invention are those having up to four carbon atoms such as, for example, methyl, propyl, iso-propyl, n-butyl, sec-butyl, methoxy, ethoxy, t-butoxy, etc.

Also embraced within the scope of the present invention are the non-toxic, pharmaceutically acceptable salts of the novel compounds of the present invention when R.sub.1 is hydroxy. The cations comprised in these salts include, for example, the non-toxic metal cations such as the sodium ion, potassium ion, calcium ion, and magnesium ion as well as the organic amine cations such as the tri(lower alkyl)amine cations (e.g., triethylamine), procaine, and the like.

The novel compounds of the present invention are obtainable as yellow oils or crystalline solids having characteristics absorption spectra. They are relatively insoluble in water but are relatively soluble in common organic solvents such as ethanol, ethyl acetate, dimethylformamide, and the like. The cationic salts of the compounds when R.sub.1 is hydroxy are, in general, white to yellow crystalline solids having characteristic absorption spectra. They are relatively soluble in water, methanol and ethanol but are relatively insoluble in benzene, diethyl ether, and petroleum ether.

The prostaglandins are a family of closely related compounds which have been obtained from various animal tissues, and which stimulate smooth muscle, lower arterial blood pressure, antagonize epinephrine-induced mobilization of free fatty acids, and have other pharmacological and autopharmacological effects in mammals. See Bergstom et al., J. Biol. Chem., 238, 3555 (1963) and Horton, Experienta, 21, 113 (1965) and references cited therein. All of the so-called natural prostaglandins are derivatives of prostanoic acid. ##STR6## The hydrogen atoms attached to C-8 and C-12 are in trans configuration. The natural prostaglandins represent only one of the possible optical isomers. The compounds of this convention include all possible optical isomers.

The novel compounds of this invention are prepared from the corresponding known 11.alpha.-hydroxy-9-oxo-5-cis,13-trans-prostadienoic acids (I) (Netherlands Pat. No. 7,206,361; Nov. 14, 1972) as illustrated in Flowsheet A which follows and in which n, R.sub.2 and C.sub.5 -C.sub.5 are as hereinabove defined and in which THP is the tetrahydropyranyl group. ##STR7##

According to Flowsheet A above, dehydration of (I) in the usual manner provides the 16-aryloxy-15.alpha.-hydroxy-9-oxo-17,20-tetranor-5-cis,10,13-trans-prosta trienoic acids (III) which upon treatment with dihydropyran and acid provide the bistetrahydropyranyl derivative (V). Upon treatment of (V) with sodium borohydride or sodium cyanoborohydride (pH3-4), a mixture (VII) of 9.alpha.,15.alpha.-dihydroxy-16-aryloxy-9-oxo-17,20-tetranor-5-cis,13-tran s-prostadienoic acid and the corresponding 9.alpha.-hydroxyl prostadienoic acid is obtained. Oxidation of the 9-hydroxy mixture (VII) provides, after acidic hydrolysis of the tetrahydropyranyl functions, the 16-aryloxy-15.alpha.-hydroxy-9-oxo-17,20-tetranor-5-cis,13-trans-prostadie noic acid (VIII), which upon hydrogenation provides the fully saturated 16-aryloxy-15.alpha.-hydroxy-9-oxo-17,20-tetranorprostanoic acids (IX).

Treatment of the 16-aryloxy-11.alpha.,15.alpha.-dihydroxy-17,20-tetranor-5-cis,13-trans-pro stadienoic acids (I) with dihydropyran and an acid catalyst provides the tris-tetrahydropyranyl derivatives (II) which can be selectively reduced at the C.sub.5 -C.sub.6 cis double bond. Acid-catalyzed hydrolysis of the tetrahydropyranyl moieties than provides the 11.alpha.,15.alpha.-dihydroxy-9-oxo-16-aryloxy-17,20-tetranor-13-trans-pro stenoic acids (IV), which when subjected to the steps as described above for I.fwdarw.III.fwdarw.V.fwdarw.VII.fwdarw.VIII provides the 15.alpha.-hydroxy-9-oxo-16-aryloxy-17,20-tetranor-13-trans-prostenoic acids of this invention.

The 9-hydroxy derivative of this invention can also be obtained by reduction of the corresponding 9-oxo derivative. When the reduction is carried out in the usual manner with sodium borohydride in ethanol as solvent, the product is a mixture of the 9.alpha.- and 9.beta.-hydroxy derivative (X) and (XI), respectively. These isomers are separable by chromatographic procedures. The stereoselective preparation of the 9.alpha.-hydroxy derivative (X) can be accomplished by reduction of the 9-oxo derivative with either lithium perhydro-9b-boraphenalyl hydride [H. C. Brown and W. C. Dickason, Jour. Amer. Chem. Soc., 92, 709 (1970)] or with lithium tri-sec-butylborohydride. ##STR8##

The carboxylic acid esters (R.sub.1 =alkoxy) of this invention can be prepared by treating the corresponding carboxylic acid with the appropriate diazoalkane by the usual procedures well known to the art. An alternative procedure involves blocking the 15-hydroxy function with a tetrahydropyranyl group, conversion of the carboxylic acid to an acid chloride and reacting with the appropriate alcohol in the presence of an acid-acceptor and deblocking.

All of the compounds of this invention can be isolated and purified by conventional methods. Isolation can be accomplished, for example, by dilution of the reaction mixture with water, extraction with a water-immiscible solvent such as methylene chloride, ethyl acetate, benzene, cyclohexane, ether, toluene and the like, chromatography, adsorption on ion-exchange resins, distillation, or a combination of these. Purification of the compounds of this invention can be accomplished by means known in the art for the purification of prostaglandins and lipids, fatty acids, and fatty esters. For example, partition chromatography, reverse phase partition chromatography, countercurrent distribution, adsorption chromatography on acid washed Florisil.RTM. (synthetic magnesium silicate) and acid washed silica gel, dry column chromatography, preparative paper chromatography, preparative thin layer chromatography, chromatography over sili-ca loaded cation exchange resins, and combinations thereof can be used effectively to purify the compounds produced by the presence of this invention.

If a compound of this invention is prepared from a prostaglandin A (III, V, VI) which is in the optically active resolved from, then the product will also be in the resolved form. On the other hand, if the prostaglandin A is racemic, the product will be racemic.

In formulae XII-XXIII, which follow, R.sub.2, n, X, C.sub.5 -C.sub.6 and C.sub.13 -C.sub.14 are as hereinabove defined.

The racemic products and intermediates of this invention may be resolved into their optically active components by a number of methods of resolution well known in the art. For example, the free carboxylic acids can be treated with an optically active base such as cinchonine, quinine, brucine, d- or l-.alpha.-phenylethylamine and the like to produce diastereoisomeric salts which can be separated by crystallization. Alternatively, the acid may be esterified with an optically active alcohol, e.g., d- or l-menthol, estradiol 3-acetate, etc., and the diastereoisomeric esters then resolved.

Resolution of the racemic prostaglandin-like compounds of this invention may also be accomplished by reverse phase and absorption chromatography on an optically active support and adsorbent and by selective transformation of one isomer with a biologically-active prostaglandin transforming system. Such transformations can be carried out by incubation or perfusion, using methods well established in the art, followed by isolation and recovery of the isomer resistant to the metabolic transformation applied.

Additional procedures for effecting the resolution of the racemic products of this invention involve conversion of a 9.alpha.-hydroxy racemate (illustrated by XII and XIII below) to the corresponding hemiphthalate (e.g., XIV) and conversion of this diacid to a bis salt (e.g., XV) with an optically active amine (e.g., l-(-)-.alpha.-methylbenzylamine, d-(+)-.alpha.-methylbenzylamine, brucine, dehydroabietylamine, strychnine, quinine, cinchonine, cinchonidine, quinidine, ephedrine, deoxyepedrine, amphetamine, (+)-2-amino-1-butanol (-)-2-amino-1-butanol and the like). The resulting diastereoisomers are then separated by fractional crystallization and the individual components are then converted by acidification and saponification to the individual optically active parent 9.alpha.-hydroxy enantiomers (XII) and (XIII), oxidation of which provides the corresponding individual 9-oxo enantiomers (XVI) and (XVII). ##STR9##

Another procedure involves conversion of the 9.alpha.-hydroxy racemate (as the 15-hydroxy blocked and then deblocked prostenoic acid ester) to the diastereomeric carbamates with an optically active isocyanate, e.g., (+)-1-phenylethylisocyanate and (-)-1-phenylethylisocyanate. Separation of the diastereomers, for example, (XVIII) and (XIX), can be accomplished by fractional crystallization or by the usual chromatographic procedures, or if necessary by high speed liquid chromatography involving, if required, recycling techniques [See G. Fallick, American Laboratory, 19-27 (August, 1973) as well as references cited therein. Additional information concerning high speed liquid chromatography and the instruments necessary for its application is available from Waters Associates Inc., Maple St., Milford, Mass.] Base-treatment of the individual diastereomeric carbamates then affords the individual enantiomeric alcohols. ##STR10##

It is also possible to effect resolution of the 9.alpha.-hydroxy racemate, preferably as the prostenoate ester, by esterification of the 9.alpha.-hydroxy function (15-hydroxy function blocked as a tetrahydropyranyl ether or trimethylsilyl ester and then deblocked after 9.alpha.-hydroxyfunctionally action) with an optically active acid, via its acid chloride. Suitable optically active acids include .omega.-camphoric acid, menthoxyacetic acid, 3.beta.-acetoxy-.DELTA..sup.5 -etianic acid, (-)-.alpha.-methoxy-.alpha.-trifluoromethylphenyl acetic acid and (+)-.alpha.-methoxy-.alpha.-trifluoromethylphenylacetic acid, and the like. The resulting diastereoisomeric esters, for example (XX) and (XXI) are then separated by fractional crystallization or by chromatographic techniques including if necessary, the use of high speed liquid chromatography. Saponification of the individual diastereoisomers then provides the individual 9.alpha.-hydroxyprostenoic acid enantiomers (XII) and (XIII). ##STR11##

Another resolution procedure involves derivatization of the keto function of the racemic 9-oxoprostenoic acid or ester with the usual type of ketone derivatizing agents bearing an optically active center. The resulting mixture of diastereomeric derivatives can then be separated by fractional crystallization or by chromatography or, if necessary, by high speed liquid chromatography. The individual diastereomeric keto derivatives, for example, (XXII) and (XXIII), are then convertable to the individual 9-oxo enantiomers (XVI) and (XVII) by any of the usual cleavage techniques. Ketone reduction of the 9-oxo-enantiomer as described hereinabove then provides the corresponding 9.alpha.-hydroxy or 9.beta.-hydroxy enantiomer. Among the optically active reagents useful for ketone derivatization are 1-.alpha.-aminoxy-.gamma.-methylpentanoic acid hydrochloride [E. Testa et al., Helv. Chimica Acta, 47 (3), 766 (1973)], menthylhydrazine, and 4-.alpha.-methylbenzylsemicarbazide. ##STR12##

Other useful keto derivatizing agents are optically active 1,2-glycols, e.g., D(-)-2,3-butanediol, [for pertinent literature see, A. C. Neish, Can. Jour. Res. 23 sec. B, 10 (1945); G. E. Ward et al., Jour. Amer. Chem. Soc., 66, 541 (1944); J. Casanova, Jr. and E. J. Corey, Chem. and Ind. (London), 1961, 1664)] or optically active dithiols, e.g., L(+)-2,3-butanedithiol [see also E. J. Corey and R. B. Miha, Jour. Amer. Chem. Soc., 84, 2938 (1962)].

The novel compounds of this invention are useful as hypotensive agents (9-oxo derivatives), bronchodilators for the treatment of asthma and as agents for the control of reproduction in females, in humans as well as in warm-blooded animals such as cattle, sheep, swine, horses, dogs and cats. Among the potential uses in domestic animals is the synchronization of estrus in cattle and other domestic animals, and the induction of twinning.

In humans these compounds may have use as agents for the induction of labor at term, as abortifacients and as menses inducers.

There are several possibilities of contraceptive attack during the normal processes of mammalian female reproduction. These include any others ovulation blockage, interference with the fertilization of the ovum by sperm, interference with the normal transport of ova and or zygotes in the reproductive tract, prevention or embryo implantation, disruption of the maternal response to embryonic implantation, and maternal failure to support embryonic survival. While the exact mechanism or mechanisms which take place with the active ingredients in effecting contraception is not clear, the compounds of this invention may prevent conception by one or more of the above-mentioned occurrences. It is not intended, however, that the present invention be limited to any particular theory as to mechanism of contraception.

A major problem in the clinical use of prostaglandin E.sub.2 and prostaglandin F.sub.2 .alpha., and indeed of prostaglandins of the 11.alpha.-hydroxy series in general, is the often high incidence of gastrointestinal side-effects as manifested by nausea, vomiting and diarrhea. Presumably, these effects result from the stimulation of gastrointestinal smooth muscle by the administered prostaglandin. One important advantage of the compounds of this invention is that although they retain to a significant extent the antifertility pot-ency of the parent 11-hydroxy compounds they show a highly diminished ability to stimulate smooth myscle. This very significant and unanticipated separation of biological effects suggests that the compounds of this invention have the potential to be useful anti-fertility agents with a minimum of adverse side-effects. It is also conceivable that this separation will allow the use of higher relative doses of these compounds than hitherto possible with the established prostaglandins. This also denotes the possibilities of more effective application in the field of post-conception control, e.g. inducing menses during approximately the first two weeks following the first missed menstruation. For a discussion of these problems see Toppozada et al. "Prostaglandins in Fertility Control" 3, 108 (1973), Report from Meetings of the Prostaglandin Task Force Steering Committee sponsored by the World Health Organization; and Wiqvist et al., ibid. 3, 83 (1973).

The invention will be described in greater detail in conjunction with the following specific examples. d,l-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13 -trans-prostadienoic acid

A mixture of the 15 epimers of dl-16-phenoxy-9.alpha.,11.alpha.,15-trihydroxy-17,20-tetranor-5-cis-13-tra ns-prostadienoic acid is prepared in accordance with Netherlands Pat. No. 7,206,361, page 9, Example 1. The two epimers are separated by the procedure of Netherlands Pat. No. 7,206,361, page 9, Example 1. The high Rf material is assigned the 15.beta. configuration and the low Rf material is assigned the 15.alpha.-configuration. dl-16-Phenoxy-9.alpha.,11.alpha.,15-trihydroxy-17,20-tetranor-5-cis-13-tra ns-prostadienoic acid (100 mg.) is dissolved in 2.0 ml. of dry acetone and stirred at -40.degree. C. under argon, N-trimethylsilyldimethylamine (3 ml.) is then added and after 1 hour the reaction is diluted with cold ether and extracted with 50% saturated aqueous sodium bicarbonate. Evaporation to dryness in vacuo yields as the major product: dl-11.alpha.,15.alpha.-bistrimethylsiloxy-9.alpha.-hydroxy-16-phenoxy-17,2 0-tetranor-5-cis-13-trans-prostadienoic acid trimethylsilyl ester.

The crude material is oxidized with Collins reagent (prepared in situ from 170 mg. of chromic anhydride and 275 ml. of pyridine in 4 ml. of methylene chloride) for 5 minutes at 25.degree. C. The reaction mixture is diluted with ether and extracted with 0.5 M hydrochloric acid washed with brine. The organic solution is dried with magnesium sulfate and concentrated in vacuo to give the crude dl-11.alpha.,15-bistrimethylsiloxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-1 3-trans-prostadienoic acid trimethylsilyl ester.

The crude trimethylsilyl ester is dissolved in 5 ml. of methanol containing 0.5 ml. of water and 0.25 ml. of acetic acid and stirred at ambient temperature for 1 hour. The solution is diluted with 5 ml. of 30% aqueous potassium hydrogen phosphate and extracted twice with 10 ml. of ether. The ether is dried with magnesium sulfate and concentrated in vacuo to afford dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13- trans-prostatrienoic acid as an oil.

The crude oil is purified by dry column chromatography on silica gel to give dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-ci s-13-trans-prostatrienoic acid.

Treatment of the compounds of the following table by the procedure of Example 1 is productive of the 9-oxo derivatives of the table. Example Starting Compound     9-Oxo Product __________________________________________________________________________ 2    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-benzyloxy- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-benzy loxy-17,20- 17,20-tetranor-5-cis,13-trans-prosta- tetranor-5-cis,13-trans-prostadienoic acid dienoic acid 3    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(2-naph- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2-na phthyloxy)- yloxy)-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 4    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-p-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-p-chl orophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 5    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-m-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-m-chl orophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 6    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-o-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-o-chl orophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 7    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(2,4- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2,4- dichloro- dichlorophenoxy)-17,20-tetranor- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 8    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-p-bromo- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-p-bro mophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 9    dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-p-fluoro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-p-flu orophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 10   dl-9.alpha.,11.alpha.,15.alpha./.beta.-trihydroxy-16-p- dl-11.alpha.,15.alpha./.beta.-dihydroxy-9-oxo-1 6-p-methylphenoxy- methylphenoxy-17,20-tetranor-5- 17,20-tetranor-5-cis,13-trans-prostadienoic cis,13-trans-prostadienoic acid acid 11   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-m- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-m-met hylphenoxy- methylphenoxy-17,20-tetranor-5- 17,20-tetranor-5-cis,13-trans-prostadienoic cis,13-trans-prostadienoic acid acid 12   dl-9.alpha.,11.alpha.,15.alpha./.beta.-trihydroxy-16-p-t- dl-11.alpha.,15.alpha./.beta.-dihydroxy-9-oxo-1 6-p-t-butyl- butylphenoxy-17,20-tetranor-5- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- cis,13-trans-prostadienoic acid dienoic acid 13   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-p-tri- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-p-tri fluoromethyl- fluoromethylphenoxy-17,20-tetranor- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 14   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-p- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-p-met hoxyphenoxy- methoxyphenoxy-17,20-tetranor-5- 17,20-tetranor-5-cis,13-trans-prostadienoic cis,13-trans-prostadienoic acid acid 15   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-o- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-o-met hoxyphenoxy- methoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 16   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-m-fluoro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-m-flu orophenoxy- phenoxy-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic prostadienoic acid    acid 17   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-o-fluoro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-o-flu orophenoxy- phenoxy-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic prostadienoic acid    acid 18   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(3,4- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(3,4- dichloro- dichlorophenoxy)-17,20-tetranor- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 19   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(2,5- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2,5- dichloro- dichlorophenoxy)-17,20-tetranor-5- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- cis,13-trans-prostadienoic acid dienoic acid 20   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-o-methyl- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-o-met hylphenoxy- phenoxy-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic acid prostadienoic acid 21   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16(2,3-d imethyl- 16-(2,3-dimethylphenoxy)-17,20- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- tetranor-5-cis,13-trans-prostadienoic acid dienoic acid 22   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(3,5- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(3,5- dimethyl- dimethylphenoxy)-17,20-tetranor- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 23   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(2-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2-ch loro-4- 4-methylphenoxy)-17,20-tetranor-5- methylphenoxy)-17,20-tetranor-5-cis,13-trans- cis,13-trans-prostadienoic acid prostadienoic acid 24   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-m-dimethyl- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-M--di methylamino- aminophenoxy-17,20-tetranor-5-cis, phenoxy-17,20-tetranor-5-cis,13-trans-prosta- 13-trans-prostadienoic acid dienoic acid 25   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(1- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(1-na phthyloxy)- naphthyloxy)-17,20-tetranor-5- 17,20-tetranor-5-cis,13-trans-prostadienoic cis,13-trans-prostadienoic acid acid 26   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(4-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(4-ch loro-1- 1-naphthyloxy)17,20-tetranor-5- naphthyloxy)-17,20-tetranor-5-cis,13-trans- cis,13-trans-prostadienoic acid prostadienoic acid 27   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(6- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(6-me thyl-2- methyl-2-naphthyloxy)-17,20-tetranor- naphthyloxy)-17,20-tetranor-5-cis,13-trans- 5-cis,13-trans-prostadienoic acid prostadienoic acid 28   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(6- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(6-me thoxy-2- methoxy-2-naphthyloxy)-17,20-tetra- naphthyloxy)-17,20-tetranor-5-cis,13-trans- nor-5-cis,13-trans-prostadienoic acid prostadienoic acid 29   dl-9.alpha.,11.alpha.,15-trihydroxy-16-(2,3-di dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2,3- dichloro- chloro)-17,20-tetranor-5-cis-13- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- trans-prostadienoic acid dienoic acid 30   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(2,6-di- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(2,6- dichloro- chlorophenoxy)-17,20-tetranor-5-cis, phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 13-trans-prostadienoic acid dienoic acid 31   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(3,5- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(3,5- dichloro- dichlorophenoxy)-17,20-tetranor- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 32   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(4-chloro- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(4-ch loro-3-methyl- 3-methylphenoxy)-17,20-tetranor-5- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- cis,13-trans-prostadienoic acid dienoic acid 33   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-m-methoxy- dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-m-met hoxyphenoxy-17, phenoxy-17,20-tetranor-5-cis,13- 20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 34   dl-9.alpha.,11.alpha.,15.alpha./.beta.-trihydroxy-16-(1- dl-11.alpha.,15.alpha./.beta.-dihydroxy-9-oxo-1 6-(1-chloro-2- chloro-2-naphthyloxy)-17,20-tetra- naphthyloxy)-17,20-tetranor-5-cis,13-trans- nor-5-cis,13-trans-prostadienoic acid prostadienoic acid 35   dl-9.alpha.,11.alpha.,15.alpha.-trihydroxy-16-(5,6,7, dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(5,6, 7,8-tetra- 8-tetrahydro-2-naphthyloxy)-17,20- hydro-2-naphthyloxy)-17,20-tetranor-5-cis,13- tetranor-5-cis,13-trans-prosta- trans-prostadienoic acid dienoic acid 36   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-benzyloxy- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-benzyl oxy-17,20- 17,20-tetranor-5-cis,13-trans-prosta- tetranor-5-cis,13-trans-prostadienoic acid dienoic acid 37   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(2-naph- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(2-nap hthyloxy)- thyloxy)-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 38   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-p-chloro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-p-chlo rophenoxy- phenoxy-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic acid prostadienoic acid 39   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-m-chloro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-m-chlo rophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 40   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-o-chloro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-o-chlo rophenoxy- phenoxy-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic acid prostadienoic acid 41   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(2,4- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(2,4-d ichloro- dichlorophenoxy)-17,20-tetranor- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 42   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-p-fluoro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-p-fluo rophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic trans-prostadienoic acid acid 43   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-m-methyl- dl-11.alpha.,15.beta.-trihydroxy-9-oxo-16-m-met hylphenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 44   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-p-tri- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-p-trif luoromethyl- fluoromethylphenoxy-17,20-tetranor- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- 5-cis,13-trans-prostadienoic acid dienoic acid 45   dl-9.alpha.,11.alpha.,15.beta.  -trihydroxy-16-p-methoxy- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-p-meth oxyphenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 46   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-o-methoxy- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-o-meth oxyphenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 47   dl-9.alpha.,11.alpha.15.beta.-trihydroxy-16-m-fluoro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-m-fluo rophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 48   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-o-fluoro- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-o-fluo rophenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 49   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-o-methyl- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-o-meth ylphenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 50   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-m-dimethyl- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-m-dime thylamino- aminophenoxy-17,20-tetranor-5-cis,13- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- trans-prostadienoic acid dienoic acid 51   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(1-naphth- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(1-nap hthyloxy)- yloxy)-17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic prostadienoic acid    acid 52   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(6- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(6-met hoxy-2- methoxy-2-naphthyloxy)-17,20-tetra- naphthyloxy)-17,20-tetranor-5-cis,13-trans- nor-5-cis,13-trans-prostadienoic acid prostadienoic acid 53   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(2,3-di- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(2,3-d ichloro- chlorophenoxy)-17,20-tetranor-5-cis, phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- 13-trans-prostadienoic acid 54   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(3,5- dl-11.alpha. ,15.beta.-dihydroxy-9-oxo-16-(3,5- dichloro- dichlorophenoxy)-17,20-tetranor-5- phenoxy)-17,20-tetranor-5-cis,13-trans-prosta- cis,13-trans-prostadienoic acid dienoic acid 55   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-m-methoxy- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-m-meth oxyphenoxy- phenoxy-17,20-tetranor-5-cis,13- 17,20-tetranor-5-cis,13-trans-prostadienoic acid trans-prostadienoic acid 56   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-(5,6,7,8- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-(5,6,7 ,8-tetra- tetrahydro-2-naphthyloxy)-17,20- hydro-2-naphthyloxy)-17,20-tetranor-5-cis, tetranor-5-cis,13-trans-prostadienoic acid 13-trans-prostadienoic acid 57   dl-9.alpha.,11.alpha.,15.beta.-trihydroxy-16-phenoxy- dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-phenox y- 17,20-tetranor-5-cis,13-trans- 17,20-tetranor-5-cis,13-trans-prostadienoic prostadienoic acid    acid __________________________________________________________________________ dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans- prostenoic acid by hydrogenation of dl-11.alpha.,15.alpha.-dihydro-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tr ans-prostadienoic acid (Example 1)

A solution of 110 mg. of dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid (Example 1) in 0.5 ml. acetone and 0.5 ml. benzene is purged with argon and 11 mg. of tris(triphenylphosphine)rhodium chloride is added. This mixture is stirred under hydrogen at 20-30 psi for 6 hours, or until a TLC (using silver nitrate impregnated silica plate) indicates the absence of any prostadienoic acid. The solvents are removed in vacuo and the oily residue is dissolved in 2 ml. methanol and poured into 10 ml. of 0.2 M sodium phosphate buffer. The mixture is extracted twice with toluene. The aqueous layers are acidified to pH 3 with 2 M citric acid, saturated with sodium chloride, and extracted twice with ether. The extracts are dried with magnesium sulfate and concentrated in vacuo to give 100 mg. of an oil.

This oil is chromatographed on acid washed silica gel to give 40 mg. of dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-13-trans- prostenoic acid; .lambda.max. 3400, 1740-1710, 975 cm.sup.-1.

Treatment of the E.sub.2 compounds of the following table by the method of Example 58 is productive of the E.sub.1 compound of the table. __________________________________________________________________________ Example E.sub.2 Compound E.sub.1 Compound __________________________________________________________________________ 59   Example 10 dl-11.alpha.,15.alpha./.beta.-dihydroxy-9-oxo-16-p-methylphen oxy-17,20- tetranor-13-trans-prostenoic acid 60   Example 11 dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-m-methylphenoxy-17, 20- tetranor-13-trans-prostenoic acid 61   Example 22 dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-(3,5-dimethylphenox y)-17, 20-tetranor-13-trans-prostenoic acid 62   Example 46 dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-o-methoxyphenoxy-17 ,20- tetranor-13-trans-prostenoic acid 63   Example 20 dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-o-methylphenoxy-17,2 0- tetranor-13-trans-prostenoic acid 64   Example 45 dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-p-methoxyphenoxy-17, 20- tetranor-13-trans-prostenoic acid 65   Example 50 dl-11.alpha.,15.beta.-dihydroxy-9-oxo-16-m-dimethylaminopheno xy- 17,20-tetranor-13-trans-prostenoic acid __________________________________________________________________________ dl-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-10,13-trans-pro statrienoic acid

A solution of 80 mg. of dl-11.alpha.,15.alpha.-dihydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis-13- trans-prostadienoic acid (Example 1) in 5 ml. of 0.5 N hydrochloric acid in 1:1 water-tetrahydrofuran for 60 hours at 25.degree. C.

The solution is diluted with 100 ml. of benzene and 50 ml. of brine is added. The organic solution is concentrated in vacuo to afford the oily product; .lambda.max: 3400, 1710, 975 cm.sup.-1, .lambda.max: 217 nm (.epsilon.=9000).

The prostaglandin E compound of the table, when submitted to the reaction conditions of Example 66 gives the prostaglandin A product of the table. __________________________________________________________________________ Example Starting E Compound Product A Compound __________________________________________________________________________ 67   Example 2  dl-15.alpha.-hydroxy-9-oxo-16-benzyloxy-17,20-tetranor- 5-cis,10,13-trans-prostatrienoic acid 68   Example 3  dl-15.alpha.-hydroxy-9-oxo-16-(2-naphthyloxy)-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 69   Example 4  dl-15.alpha.-hydroxy-9-oxo-16-p-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 70   Example 5  dl-15.alpha.-hydroxy-9-oxo-16-o-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 71   Example 6  dl-15.alpha.-hydroxy-9-oxo-16-o-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 72   Example 7  dl-15.alpha.-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 73   Example 8  dl-15.alpha.-hydroxy-9-oxo-16-p-bromophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 74   Example 9  dl-15.alpha.-hydroxy-9-oxo-16-p-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 75   Example 10 dl-15.alpha./.beta.-hydroxy-9-oxo-16-p-methylphenoxy-17,20 - tetranor-5-cis,10,13-trans-prostatrienoic acid 76   Example 11 dl-15.alpha.-hydroxy-9-oxo-16-m-methylphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 77   Example 12 dl-15.alpha./.beta.-hydroxy-9-oxo-16-p-t-butylphenoxy-17,2 0- tetranor-5-cis,10,13-trans-prostatrienoic acid 78   Example 13 dl-15.alpha.-hydroxy-9-oxo-16-p-trifluoromethylphenoxy- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 79   Example 14 dl-15.alpha.-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 80   Example 15 dl-15.alpha.-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 81   Example 16 dl-15.alpha.-hydroxy-9-oxo-16-m-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 82   Example 17 dl-15.alpha.-hydroxy-9-oxo-16-o-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 83   Example 18 dl-15.alpha.-hydroxy-9-oxo-16-(3,4-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 84   Example 19 dl-15.alpha.-hydroxy-9-oxo-16-(2,5-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 85   Example 20 dl-15.alpha.-hydroxy-9-oxo-16-o-methylphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 86   Example 21 dl-15.alpha.-hydroxy-9-oxo-16-(2,3-dimethylphenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 87   Example 22 dl-15.alpha.-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 88   Example 23 dl-15.alpha.-hydroxy-9-oxo-16-(2-chloro-4-methylphenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 89   Example 24 dl-15.alpha.-hydroxy-9-oxo-16-m-dimethylaminophenoxy- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 90   Example 25 dl-15.alpha.-hydroxy-9-oxo-16-(1-naphthyloxy)-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 91   Example 26 dl-15.alpha.-hydroxy-9-oxo-16-(4-chloro-1-naphthyloxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 92   Example 27 dl-15.alpha.-hydroxy-9-oxo-16-(6-methyl-2-naphthyloxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 93   Example 28 dl-15.alpha.-hydroxy-9-oxo-16-(6-methoxy-2-naphthyloxy- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 94   Example 29 dl-15.alpha.-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 95   Example 30 dl-15.alpha.-hydroxy-9-oxo-16-(2,6-dichlorophenoxy)-17, 20-tetranor-5-cis,10,13-trans-prostatrienoic acid 96   Example 31 dl-15.alpha.-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 97   Example 32 dl-15.alpha.-hydroxy-9-oxo-16-(4-chloro-3-methylphenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 98   Example 33 dl-15.alpha.-hydroxy-9-oxo-16-m-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 99   Example 34 dl-15.alpha./.beta.-hydroxy-9-oxo-16-(1-chloro-2-naphthylo xy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 100  Example 35 dl-15.alpha.-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-2- naphthyloxy)-17,20-tetranor-5-cis,10,13-trans- prostatrienoic acid 101  Example 36 dl-15.beta.-hydroxy-9-oxo-16-benzyloxy-17,20-tetranor- 5-cis,10,13-trans-prostatrienoic acid 102  Example 37 dl-15.beta.-hydroxy-9-oxo-16-(2-naphthyloxy)-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 103  Example 38 dl-15.beta.-hydroxy-9-oxo-16-p-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 104  Example 39 dl-15.beta.-hydroxy-9-oxo-16-m-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 105  Example 40 dl-15.beta.-hydroxy-9-oxo-16-o-chlorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 106  Example 41 dl-15.beta.-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 107  Example 42 dl-15.beta.-hydroxy-9-oxo-16-p-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 108  Example 43 dl-15.beta.-hydroxy-9-oxo-16-m-methylphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 109  Example 44 dl-15.beta.-hydroxy-9-oxo-16-p-trifluoromethylphenoxy- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 110  Example 45 dl-15.beta.-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 111  Example 46 dl-15.beta.-hydroxy-9-oxo-16-o-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 112  Example 47 dl-15.beta.-hydroxy-9-oxo-16-m-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 113  Example 48 dl-15.beta.-hydroxy-9-oxo-16-o-fluorophenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 114  Example 49 dl-15.beta.-hydroxy-9-oxo-16-o-methylphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 115  Example 50 dl-15.beta.-hydroxy-9-oxo-16-m-dimethylaminophenoxy- 17,20-tetranor-5-cis,10,13-trans-prostatrienoic acid 116  Example 51 dl-15.beta.-hydroxy-9-oxo-16-(1-naphthyloxy)-17,20-tetra- N nor-5-cis,10,13-trans-prostatrienoic acid 117  Example 52 dl-15.beta.-hydroxy-9-oxo-16-(6-methoxy-2-naphthyloxy)-17, O 20-tetranor-5-cis,10,13-trans-prostatrienoic acid 118  Example 53 dl-15.beta.-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)-17, 20-tetranor-5-cis,10,13-trans-prostatrienoic acid 119  Example 54 dl-15.beta.-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)-17, 20-tetranor-5-cis,10,13-trans-prostatrienoic acid 120  Example 55 dl-15.beta.-hydroxy-9-oxo-16-m-methoxyphenoxy-17,20- tetranor-5-cis,10,13-trans-prostatrienoic acid 121  Example 56 dl-15.beta.-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro-2- naphthyloxy)-17,20-tetranor-5-cis,10,13-trans- prostatrienoic acid 122  Example 57 dl-15.beta.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor- 5-cis,10,13-trans-prostatrienoic acid 123  Example 58 dl-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor- 10,13-trans-prostadienoic acid 124  Example 60 dl-15.alpha.-hydroxy-9-oxo-16-m-methylphenoxy-17,20- tetranor-10,13-trans-prostadienoic acid 125  Example 61 dl-15.alpha.-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)- 17,20-tetranor-10,13-trans-prostadienoic acid 126  Example 62 dl-15.beta.-hydroxy-9-oxo-16-O--methoxyphenoxy-17,20- tetranor-10,13-trans-prostadienoic acid 127  Example 63 dl-15.alpha.-hydroxy-9-oxo-16-O--methylphenoxy-17,20- tetranor-10,13-trans-prostadienoic acid 128  Example 64 dl-15.beta.-hydroxy-9-oxo-16-p-methoxyphenoxy-17,20- tetranor-10,13-trans-prostadienoic acid 129  Example 65 dl-15.beta.-hydroxy-9-oxo-16-m-dimethylaminophenoxy- 17,20-tetranor-10,13-trans-prostadienoic acid 129a Example 59 dl-11.alpha.,15.alpha./.beta.-dihydroxy-9-oxo-16-p-methylp henoxy- 17,20-tetranor-10,13-trans-prostadienoic __________________________________________________________________________ acid dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid

150 mg. of dl-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-pro statrienoic acid (Example 66) in 10 ml. of ether is esterified with excess diazomethane in ether. Evaporation of the ether gives dl-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-pro statrienoic acid methyl ester.

The crude methyl ester is dissolved in 10 ml. of benzene and 7 ml. of a 1 N solution of acetic anhydride-pyridine in benzene is added. After 24 hours 5 ml. more of 1 N acetic anhydride-piperidine is added and stirred. After an additional 24 hours, 5 ml. more of 1 N acetic anhydride-pyridine is added and stirred 72 hours or until TLC indicates no starting material present. The volume of the reaction is reduced to 10 ml. in vacuo on a rotary evaporator. The reaction product is chromatographed on acid washed silica-gel with ethyl acetate-benzene to provide dl-15.alpha.-acetoxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,10,13-trans-pro statrienoic acid methyl ester as an oil.

The crude methyl ester is dissolved in 3 ml. of ethanol at 0.degree. C. and is treated dropwise with a cold solution of 230 mg. of sodium borohydride in 3 ml. of ethanol containing 0.3 ml. of water. After 15 minutes, 0.25 ml. of acetic acid and 10 ml. of water is added, and the mixture is extracted with 50 ml. of methylene chloride. The organic extract is washed with sodium bicarbonate, dried with magnesium sulfate, and concentrated in vacuo to give an oil.

The crude oil is dissolved in 8 ml. of acetone and cooled to -5.degree. C. Then 0.3 ml. of Jones chromic oxide mixture is added slowly and after 15 minutes 0.1 ml. of isopropanol is added.

After 5 minutes the solution is diluted with 25 ml. of methylene chloride and washed with 20 ml. of water. The methylene chloride is dried with magnesium sulfate and concentrated in vacuo to give the crude mixture as an oil.

The oil is purified on acid washed silica-gel using benzene-ethyl acetate to give dl-15.alpha.-acetoxy-11-deoxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid methyl ester as an oil.

To 50 mg. of the methyl ester in 2 ml. of methanol is added 1 ml. of 2.5 N aqueous sodium hydroxide. After stirring for 8 hours, the solution is acidified with 30% aqueous sodium dihydrogen phosphate, saturated with sodium chloride, and extracted with ether. The ether extracts are dried with magnesium sulfate and concentrated in vacuo to give dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid; 3400, 1735, 1710, 975 cm.sup.-1.

Treatment of the A type compounds of the table by the method of Example 130 is productive of the 11-deoxy compounds of the table. __________________________________________________________________________ Starting Example Prostaglandin A 11-Deoxy Product __________________________________________________________________________ 131  Example 67 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-benzyloxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 132  Example 68 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2-naphthyloxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 133  Example 69 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 134  Example 70 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 135  Example 71 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-o-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 136  Example 72 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 137  Example 73 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-bromophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 138  Example 74 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 139  Example 75 dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-p-methylphenoxy - 17,20-tetranor-5-cis,13-trans-prostadienoic acid 140  Example 76 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 141  Example 77 dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-p-t-butylphenox y- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 142  Example 78 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-trifluoromethyl- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 143  Example 79 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 144  Example 80 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-o-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 145  Example 81 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 146  Example 82 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-o-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 147  Example 83 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(3,4-dichlorophenoxy)- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 148  Example 84 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2,5-dichlorophenoxy)- O 17,20-tetranor-5-cis,13-trans-prostadienoic acid 149  Example 85 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-O--methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 150  Example 86 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2,3-dimethyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 151  Example 87 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(3,5-dimethyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 152  Example 88 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2-chloro-4-methyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 153  Example 89 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-dimethylaminophenoxy - 17,20-tetranor-5-cis,13-trans-prostadienoic acid 154  Example 90 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(1-naphthyloxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 155  Example 91 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(4-chloro-1-naphthylox y)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 156  Example 92 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(6-methyl-2-naphthylox y)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 157  Example 93 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(6-methoxy-2-naphth- yloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 158  Example 94 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 159  Example 95 dl-11-deoxy-15.alpha. -hydroxy-9-oxo-16-(2,6-dichlorophenoxy) - 17,20-tetranor-5-cis,13-trans-prostadienoic acid 160  Example 96 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 161  Example 97 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(4-chloro-3-methyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 162  Example 98 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 163  Example 99 dl-11-deoxy-15.alpha./-hydroxy-9-oxo-16-(1-chloro-2-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 164  Example 100 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro- 2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid 165  Example 101 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-benzyloxy-17,20-tetra- nor-5-cis,13-trans-prostadienoic acid 166  Example 102 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(2-naphthyloxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 167  Example 103 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 168  Example 104 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 169  Example 105 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-o-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 170  Example 106 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(2,4-dichlorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 171  Example 107 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 172  Example 108 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 173  Example 109 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-trifluoromethyl- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 174  Example 110 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 175  Example 111 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 176  Example 112 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 177  Example 113 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-o-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 178  Example 114 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-o-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 179  Example 115 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-dimethylaminophenoxy- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 180  Example 116 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(1-naphthyloxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 181  Example 117 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(6-methoxy-2-naphthyl- O oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 182  Example 118 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(2,3-dichlorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 183  Example 119 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(3,5-dichlorophenoxy)- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 184  Example 120 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 185  Example 121 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-(5,6,7,8-tetrahydro- 2-naphthyloxy)-17,20-tetranor-5-cis,13-trans- prostadienoic acid 186  Example 122 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-phenoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 187  Example 123 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20- tetranor-13-trans-prostenoic acid 188  Example 129a dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-p-methylphenoxy - 17,20-tetranor-13-trans-prostenoic acid 189  Example 124 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 190  Example 125 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(3,5-dimethylphenoxy)- 17,20-tetranor-13-trans-prostenoic acid 191  Example 126 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-o-methoxyphenoxy- 17,20-tetranor-13-trans-prostenoic acid 192  Example 127 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-o-methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 193  Example 128 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-methoxyphenoxy- 17,20-tetranor-13-trans-prostenoic acid 194  Example 129 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-dimethylamino- phenoxy-17,20-tetranor-13-trans-prostenoic __________________________________________________________________________ acid dl-11-deoxy-9-oxo-15.alpha.-hydroxy-16-phenoxy-17,20-tetranor-prostanoic acid

A solution of 900 mg. of dl-11-deoxy-9-oxo-15.alpha.-hydroxy-16-phenoxy-17,20-tetranor-13-trans-pro stenoic acid (Example 187) in 1 ml. of acetone and 1 ml. of benzene was purged with nitrogen and 0.1 gm. of tris(triphenylphosphine)rhodium chloride is added. The mixture is shaken under 20-30 pounds of hydrogen for 12 hours. The mixture is diluted with 50 ml. of 5% aqueous sodium carbonate and extracted with 10 ml. of toluene. The aqueous solution is acidified to pH 4 with 2 N aqueous hydrochloric acid saturated with sodium chloride, and extracted twice with 50 ml. of ether. The ether is dried with magnesium sulfate and concentrated in vacuo to give dl-11-deoxy-9-oxo-16-phenoxy-17,20-tetranorprostanoic acid; max. 3400, 1735 cm.sup.-1.

Hydrogenation of the E.sub.1 compounds of the following table by the procedure of Example 195 is productive of the 13-dihydro compounds of the table. __________________________________________________________________________ Starting Example 13-trans-prostenoic acid Product Prostanoic Acid __________________________________________________________________________ 196  Example 188 dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-p-methylphe noxy- 17,20-tetranor-prostanoic acid 197  Example 189 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-methylphenoxy- 17,20-tetranor-prostanoic acid 198  Example 190 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-(3,5-dimethylpheno xy)- 17,20-tetranor-prostanoic acid 199  Example 191 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-O--methoxyphenoxy- 17,20-tetranor-prostanoic acid 200  Example 192 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-O--methylphenoxy- 17,20-tetranor-prostanoic acid 201  Example 193 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-p-methoxyphenoxy- 17,20-tetranor-prostanoic acid 202  Example 194 dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-dimethylaminophen oxy- 17,20-tetranor-prostanoic acid __________________________________________________________________________ dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,1 3-trans-prostadienoic acid

To 5 ml. of a -78.degree. C. solution of 1 M lithium-tri-sec-butylborohydride in tetrahydrofuran is added slowly a cold solution of 600 mg. of dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid in 5 ml. of tetrahydrofuran. After 20 minutes at -78.degree. C., 2 ml. of 2.5 N aqueous sodium hydroxide is added and the solution is stirred in a 30.degree. C. bath for 40 minutes. The solution is diluted with 10 ml. of water and extracted three times with 20 ml. of ether.

The aqueous solution is acidified to pH 4 with 6 N hydrochloric acid, saturated with sodium chloride and extracted twice with 50 ml. of ether. The ether extracts are combined, dried with magnesium sulfate and concentrated in vacuo to give dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,1 3-trans-prostadienoic acid; .lambda.max. 3400, 1710, 975 cm.sup.-1.

Treatment of the 9-oxo compounds of the following table by the method of Example 203 is productive of the 9.alpha.-hydroxy compounds of the table. __________________________________________________________________________ Example 9-Oxo Compound 9.alpha.-Hydroxy Product __________________________________________________________________________ 204  Example 131 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-benzyl-17,20-tet ranor- 5-cis,13-trans-prostadienoic acid 205  Example 132 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2-naphthyloxy)- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 206  Example 133 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-chlorophenoxy- O 17,20-tetranor-5-cis,13-trans-prostadienoic acid 207  Example 134 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 208  Example 135 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-o-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 209  Example 136 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2,4-dichlorophe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 210  Example 137 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-bromophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 211  Example 138 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 212  Example 139 dl-11-deoxy-9.alpha.,15.alpha./.beta.-dihydroxy-16-p-methylp henoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 213  Example 140 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-methylphenoxy- O 17,20-tetranor-5-cis,13-trans-prostadienoic acid 214  Example 141 dl-11-deoxy-9.alpha.,15.alpha./.beta.-dihydroxy-16-p-t-butyl phenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 215  Example 142 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-trifluoromethy l- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 216  Example 143 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-methoxyphenoxy - 17,20-tetranor-5-cis,13-trans-prostadienoic acid 217  Example 144 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-o-methoxyphenoxy - 17,20-tetranor-5-cis,13-trans-prostadienoic acid 218  Example 145 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-fluorophenoxy- O 17,20-tetranor-5-cis,13-trans-prostadienoic acid 219  Example 146 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-o-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 220  Example 147 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(3,4-dichlorophe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 221  Example 148 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2,5-dichlorophe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 222  Example 149 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-o-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 223  Example 150 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2,3-dimethylphe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 224  Example 151 dl-11-deoxy-11.alpha.,15.alpha.-dihydroxy-16-(3,5-dimethylph enoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 225  Example 152 dl-11-deoxy-11.alpha.,15.alpha.-dihydroxy-16-(2-chloro-4-met hyl- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 226  Example 153 dl-11-deoxy-11.alpha.,15.alpha.-dihydroxy-16-m-dimethylamino - phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 227  Example 154 dl-11-deoxy-11.alpha.,15.alpha.-dihydroxy-16-(1-naphthyloxy) -17, 20-tetranor-5-cis,13-trans-prostadienoic acid 228  Example 155 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(4-chloro-1-naph thyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 229  Example 156 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(6-methyl-2-naph thyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 230  Example 157 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(6-methoxy-2-nap hthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 231  Example 158 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2,3-dichlorophe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 232  Example 159 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(2,6-dichlorophe noxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 233  Example 160 dl-11-deoxy-9.alpha.  ,15.alpha.-dihydroxy-16-(3,5-dichlorop henoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 234  Example 161 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(4-chloro-3-meth yl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 235  Example 162 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-methoxyphenoxy -17,20- tetranor-5-cis,13-trans-prostadienoic acid 236  Example 163 dl-11-deoxy-9.alpha.,15.alpha./.beta.-dihydroxy-16-(1-chloro -2-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 237  Example 164 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(5,6,7,8-tetrahy dro- 2-naphthyloxy)17,20-tetranor-5-cis,13-trans-prosta- dienoic acid 238  Example 165 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-benzyloxy-17,20-t etra- nor-5-cis,13-trans-prostadienoic acid 239  Example 166 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(2-naphthyloxy)-1 7,20- tetranor-5-cis,13-trans-prostadienoic acid 240  Example 167 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-chlorophenoxy-1 7,20- tetranor-5-cis,13-trans-prostadienoic acid 241  Example 168 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-chlorophenoxy- 5 17,20-tetranor-5-cis,13-trans-prostadienoic acid 242  Example 169 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-O-chlorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 243  Example 170 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(2,4-dichlorophen oxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 244  Example 171 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-fluorophenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 245  Example 172 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 246  Example 173 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-trifluoromethyl - phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 247  Example 174 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-methoxyphenoxy- N 17,20-tetranor-5-cis,13-trans-prostadienoic acid 248  Example 175 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-O-methoxyphenoxy- O 17,20-tetranor-5-cis,13-trans-prostadienoic acid 249  Example 176 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-fluorophenoxy-1 7,20- tetranor-5-cis,13-trans-prostadienoic acid 250  Example 177 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-O-fluorophenoxy-1 7,20- tetranor-5-cis,13-trans-prostadienoic acid 251  Example 178 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-o-methylphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 252  Example 179 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-dimethylamino- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 253  Example 180 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(2-naphthyloxy)-1 7-20- tetranor-5-cis,13-trans-prostadienoic acid 254  Example 181 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(6-methoxy-2-naph thyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 255  Example 182 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(2,3-dichlorophen oxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 256  Example 183 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(3,5-dichlorophen oxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 257A Example 184 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-methoxyphenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 257B Example 185 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-(5,6,7,8-tetrahyd ro- 2-naphthyloxy)-17,20-tetranor-5-cis,13-trans- prostadienoic acid 257C Example 186 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-phenoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 258  Example 187 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-phenoxy-17,20- tetranor-13-trans-prostenoic acid 259  Example 189 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 260  Example 190 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(3,5-dimethylphe noxy)- 17,20-tetranor-13-trans-prostenoic acid 261  Example 191 dl-11-deoxy-9.alpha.  ,15.beta.-dihydroxy-16-O-methoxyphenox y- 17,20-tetranor-13-trans-prostenoic acid 262  Example 192 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-O-methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 263  Example 193 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-methoxyphenoxy- 17,20-tetranor-13-trans-prostenoic acid 264  Example 194 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-dimethylamino- phenoxy-17,20-tetranor-13-trans-prostenoic acid 265  Example 195 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20- tetranor-prostanoic acid 266  Example 196 dl-11-deoxy-9.alpha.,15.alpha./.beta.-dihydroxy-16-p-methylp henoxy- 17,20-tetranor-13-trans-prostenoic acid 267  Example 197 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 268  Example 198 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-(3,5-dimethylphe noxy)- 17,20-tetranor-13-trans-prostenoic acid 269  Example 199 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-O-methoxyphenoxy- u 17,20-tetranor-13-trans-prostenoic acid 270  Example 200 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-O-methylphenoxy- g 17,20-tetranor-13-trans-prostenoic acid 271  Example 201 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-p-methoxyphenoxy- . 17,20-tetranor-13-trans-prostenoic acid 272  Example 202 dl-11-deoxy-9.alpha.,15.beta.-dihydroxy-16-m-dimethylaminoph enoxy- 17,20-tetranor-13-trans-prostenoic acid __________________________________________________________________________ dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor- 5-cis,13-trans-prostadienoic acid and separation of the 9.alpha. and 9.beta. components

To a 0.degree. C. solution of 500 mg. of dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid in 10 ml. of ethanol is added 100 mg. of sodium borohydride. After 30 minutes the solution is diluted with 50 ml. of saturated aqueous ammonium chloride and extracted twice with 50 ml. of ether. The ether is dried with magnesium sulfate and concentrated in vacuo to give a nearly 1:1 mixture of the 9.alpha. and 9.beta. diols.

The diol mixture is placed onto a dry column of acid washed silica and developed with ethyl acetate-benzene.

The high Rf compound is isolated and is dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,1 3-trans-prostadienoic acid. The lower Rf, more polar isomer, is dl-11-deoxy-9.beta.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13 -trans-prostadienoic acid; the infrared spectrum of each is identical; 3400, 1700, 975 cm.sup.-1.

Treatment of the 9-oxo compounds of the following table with sodium borohydride followed by separation by the method of Example 273 is productive of the separated 9,15-diols of the table. __________________________________________________________________________ Example 9-Oxo Compound Product 9,15-Diols __________________________________________________________________________ 274  Example 131 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-benzyloxy -17,20- tetranor-5-cis,13-trans-prostadienoic acid 275  Example 132 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2-naphth yloxy)-17,20- tetranor-5-cis,13-trans-prostadienoic acid 276  Example 133 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-p-chlorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 277  Example 134 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-chlorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 278  Example 135 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-o-chlorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 279  Example 136 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2,4-dich lorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 280  Example 137 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-p-bromoph enoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 281  Example 138 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-p-fluorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 282  Example 139 dl-11-deoxy-9.alpha./.beta.,15.alpha./.beta.-dihydroxy-16-p- methylphenoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 283  Example 140 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-m-methylphenoxy- 17,20- tetranor-5-cis,13-trans-prostadienoic acid 284  Example 141 dl-11-deoxy-9.alpha.,15.alpha./.beta.- dihydroxy-16-p-t-buty lphenoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 285  Example 142 dl-11-deoxy-9.alpha.,15.alpha.-dihydroxy-16-p-trifluoromethy l- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 286  Example 143 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-p-methoxy phenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 287  Example 144 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-O-methoxy phenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 288  Example 145 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-fluorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 289  Example 146 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-O-fluorop henoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 290  Example 147 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(3,4-dich lorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 291  Example 148 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2,5-dich lorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 292  Example 149 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-O-methylp henoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 293  Example 150 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2,3-dime thylphenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 294  Example 151 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(3,5-dime thylphenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 295  Example 152 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2-chloro -4-methyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 296  Example 153 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-dimethy lamino- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 297  Example 154 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(1-naphth yloxy)-17,20- tetranor-5-cis,13-trans-prostadienoic acid 298  Example 155 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(4-chloro -1-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 299  Example 156 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(6-methyl -2-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 300  Example 157 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(6-methox y-2-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 301  Example 158 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(2,3-dich lorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 302  Example 159 dl-11-deoxy-9.alpha.  /.beta.,15.alpha.-dihydroxy-16-(2,6-di chlorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 303  Example 160 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(3,5-dich lorophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 304  Example 161 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(4-chloro -3-methyl- phenoxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 305  Example 162 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-methoxy phenoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 306  Example 163 dl-11-deoxy-9.alpha./.beta.,15.alpha./.beta.-dihydroxy-16-(1 -chloro-2- naphthyloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 307  Example 164 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(5,6,7,8- tetranor-2- naphthyloxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 308  Example 165 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-benzyloxy- 17,20-tetra- nor-5-cis,13-trans-prostadienoic acid 309  Example 166 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(2-naphthy loxy)-17,20- tetranor-5-cis,13-trans-prostadienoic acid 310  Example 167 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-chloroph enoxy-17,20- tetranor-5-cis,13-trans-prostadienoic acid 311  Example 168 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-chloroph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 312  Example 169 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-O-chloroph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 313  Example 170 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(2,4-dichl orophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 314  Example 171 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-fluoroph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 315  Example 172 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-methylph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 316  Example 173 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-trifluor omethyl- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 317  Example 174 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-methoxyp henoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 318  Example 175 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-o-methoxyp henoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 319  Example 176 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-fluoroph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 320  Example 177 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-o-fluoroph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 321  Example 178 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-o-methylph enoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 322  Example 179 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-dimethyl amino- phenoxy-17,20-tetranor-5-cis,13-trans-prostadienoic acid 323  Example 180 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(1-naphthy loxy)-17,20- tetranor-5-cis,13-trans-prostadienoic acid 324  Example 181 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(6-methoxy -2-naphthyl- oxy)-17,20-tetranor-5-cis,13-trans-prostadienoic acid 325  Example 182 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(2,3-dichl orophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 326  Example 183 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(3,5-dichl orophenoxy)- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 327  Example 184 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-methoxyp henoxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid 328  Example 185 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-(5,6,7,8-t etrahydro- 2-naphthyloxy)-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid 329  Example 186 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-phenoxy-17 ,20- tetranor-5-cis,13-trans-prostadienoic acid 330  Example 187 dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20- tetranor-13-trans-prostenoic acid 331  Example 188 dl-11-deoxy-9.alpha./.beta.,15.alpha./.beta.-dihydroxy-16-p- methylphenoxy- 17,20-tetranor-13-trans-prostenoic acid 332  Example 189 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-methylp henoxy- 17,20-tetranor-13-trans-prostenoic acid 333  Example 190 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-(3,5-dime thyl- phenoxy)-17,20-tetranor-13-trans-prostenoic acid 334  Example 191 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-O-methoxyp henoxy- 17,20-tetranor-13-trans-prostenoic acid 335  Example 192 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-O-methylp henoxy- 17,20-tetranor-13-trans-prostenoic acid 336  Example 193 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-methoxyp henoxy- 17,20-tetranor-13-trans-prostenoic acid 337  Example 194 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-dimethyl amino- phenoxy-17,20-tetranor-13-trans-prostenoic acid 338  Example 195 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-phenoxy- 1 17,20-tetranor-prostanoic acid 339  Example 196 dl-11-deoxy-9.alpha./.beta.,15.alpha./.beta.-dihydroxy-16-p- methylphenoxy- 17,20-tetranor-prostanoic acid 340  Example 197 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-m-methylp henoxy- 17,20-tetranor-prostanoic acid 341  Example 198 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-)3,5-dime thyl- phenoxy)-17,20-tetranor-prostanoic acid 342  Example 199 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-o-methoxyp henoxy- 17,20-tetranor-prostanoic acid 343  Example 200 dl-11-deoxy-9.alpha./.beta.,15.alpha.-dihydroxy-16-o-methylp henoxy- 17,20-tetranor-prostanoic acid 344  Example 201 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-p-methoxyp henoxy- 17,20-tetranor-prostanoic acid 345  Example 202 dl-11-deoxy-9.alpha./.beta.,15.beta.-dihydroxy-16-m-dimethyl amino- phenoxy-17,20-tetranor-prostanoic acid __________________________________________________________________________ dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid methyl ester

150 mg. of dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-phenoxy-17,20-tetranor-5-cis,13-tra ns-prostadienoic acid is dissolved in 10 ml. of ether, cooled to 0.degree. C. and an ethereal diazomethane solution is added until a persistant yellow color is observed. The excess diazomethane and solvent is removed under a stream of argon to provide the subject compound; .lambda.max. 3400, 1740, 975 cm.sup.-1.

The compounds of the following table when esterified with the appropriate diazoalkane by the procedure of Example 346 provide the product prostaglandin esters of the following table. __________________________________________________________________________ Example Starting Acid Diazoalkane Product Prostaglandin Ester __________________________________________________________________________ 347  Example 131 diazoethane dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-benzyloxy- 17,20-tetranor-5-cis,13-trans-prostadienoic acid ethyl ester 348  Example 134 diazopropane dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-m-chloro- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid propyl ester 349  Example 138 diazobutane dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-fluoro- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid butyl ester 350  Example 142 diazopentane dl-11-deoxy-15.alpha.-hydroxy-9-oxo-16-p-trifluoro- methylphenoxy-17,20-tetranor-5-cis,13-trans- prostadienoic acid pentyl ester 351  Example 163 diazohexane dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-(1-chloro - 2-naphthyloxy)-17,20-tetranor-5-cis,13- trans-prostadienoic acid hexyl ester 352  Example 172 diazoheptane dl-11-deoxy-15.beta.-hydroxy-9-oxo-16-m-methyl- phenoxy-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid heptyl ester 353  Example 188 diazooctane dl-11-deoxy-15.alpha./.beta.-hydroxy-9-oxo-16-p-methyl- O phenoxy-17,20-tetranor-13-trans-prostatenoic acid octyl ester 354  Example 202 diazononane dl-11-deoxy-9-oxo-15.alpha.-hydroxy-16-m-dimethyl- aminophenoxy-17,20-tetranor-prostanoic acid nonyl ester 355  Example 207 diazodecane dl-11-deoxy-9-.alpha.,15.alpha.-dihydroxy-16-m-chloro- e phenoxy-17,20-tetranor-5-cis,13-trans-prosta- dienoic acid decyl ester 356  Example 316 diazomethane dl-11-deoxy-9.beta.-15.beta.-dihydroxy-16-p-trifluoro- c methylphenoxy-17,20-tetranor-5-cis,13-trans- prostadienoic acid methyl ester __________________________________________________________________________

## Claims

1. A compound of the formula: ##STR13## wherein R.sub.1 is hydroxy or alkoxy having from 1 to 12 carbon atoms; R.sub.2 is phenyl, benzyl, napthyl, or 5, 6, 7, 8-tetrahydronapthyl optionally substituted with one or two members selected from the group halogen, lower alkyl, lower alkoxy or dimethylamino; n is an integer of from 2 to 4 inclusive, C.sub.6 -C.sub.5 is ethylene or cis-vinylene; C.sub.13 -C.sub.14 is ethylene or trans-vinylene, with the proviso that when C.sub.6 -C.sub.5 is cis-vinylene, then C.sub.13 -C.sub.14 must be trans-vinylene; X is a divalent moiety selected from the group ##STR14## Y is a divalent moiety selected from the group ##STR15## and the non-toxic cationic salts thereof where R.sub.1 is hydroxy.

2. A compound according to claim 1 wherein R.sub.1 is hydroxy or alkoxy having from 1 to 12 carbon atoms; R.sub.2 is phenyl, benzyl, napthyl or 5, 6, 7, 8-tetrahydronaphthyl optionally substituted with one or two members selected from the group halogen, lower alkyl, lower alkoxy or dimethylamino; n is an integer of from 2 to 4 inclusive, C.sub.6 -C.sub.5 is cis-vinylene; C.sub.13 -C.sub.14 is transvinylene, X is a divalent moiety selected from the group ##STR16## Y is a divalent moiety selected from the group ##STR17## and the non-toxic cationic salts thereof where R.sub.1 is hydroxy.

3. The compound of claim 1 wherein R.sub.2 is phenyl optionally substituted with one member selected from the group chloro or fluoro.

4. The compound of claim 1 wherein R.sub.1 is hydroxy or alkoxy of one or two carbon atoms and when R.sub.1 is hydroxy, the non-toxic salts thereof.

5. The enantiomer according to claim 1 that is l-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,-13-trans-p rostadienoic acid methyl ester.

6. The racemate according to claim 1 that is dl-9.alpha.,15.alpha.-dihydroxy-16-phenoxy-17,20-tetranor-5-cis,13-trans-p rostadienoic acid methyl ester.

7. The enantiomer according to claim 1 that is l-9.alpha.,15.alpha.-dihydroxy-16-o-fluorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

8. The racemate according to claim 1 that is dl-9.alpha.,15.alpha.-dihydroxy-16-o-fluorophenoxy-17,20-tetranor-5-cis,13 -trans-prostadienoic acid.

9. The enantiomer according to claim 1 that is l-9.alpha.,15.beta.-dihydroxy-16-p-fluorophenoxy-17,20-tetranor-5-cis,13-t rans-prostadienoic acid.

10. The racemate according to claim 1 that is dl-9.alpha.,15.beta.-dihydroxy-16-p-fluorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

11. The enantiomer according to claim 1 that is l-9.alpha.,15.alpha.-dihydroxy-16-o-chlorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

12. The racemate according to claim 1 that is dl-9.alpha.,15.alpha.-dihydroxy-16-o-chlorophenoxy-17,20-tetranor-5-cis,13 -trans-prostadienoic acid.

13. The enantiomer according to claim 1 that is l-9.alpha.,15.alpha.-dihydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

14. The racemate according to claim 1 that is dl-9.alpha.,15.alpha.-dihydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13 -trans-prostadienoic acid.

15. The enantiomer according to claim 1 that is l-9.alpha.,15.beta.-dihydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13-t rans-prostadienoic acid.

16. The racemate according to claim 1 that is dl-9.alpha.,15.beta.-dihydroxy-16-m-chlorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

17. The enantiomer according to claim 1 that is l-9.alpha.,15.alpha.-dihydroxy-16-p-chlorophenoxy-17,20-tetranor-5-cis,13- trans-prostadienoic acid.

18. The racemate according to claim 1 that is dl-9.alpha.,15.alpha.-dihydroxy-16-p-chlorophenoxy-17,20-tetranor-5-cis,13 -trans-prostadienoic acid.

19. The compound of claim 1 wherein n is 3, and X is ##STR18##

20. The compound of claim 1 or 19 wherein Y is ##STR19##

21. The compound of claim 1 wherein X is ##STR20##

22. The compound of claim 1 or 19 wherein R.sub.2 is phenyl.

23. The compound of claim 1 or 19 wherein C.sub.6 -C.sub.5 is ethylene and C.sub.13 -C.sub.14 is trans-vinylene.