Novel 16-aryloxy-17,18,19,20-tetranorprostanoic acids and derivatives

#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.

#The invention will be described in greater detail in conjunction with the following specific examples.

#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.