PROCESS FOR PREPARING PROSTAGLANDINES

1456511 Prostaglandins PFIZER Inc 1 Nov 1973 [8 Nov 1972] 50889/73 Heading C2C The invention comprises prostaglandins of the formula I and the C 15 epimers thereof, wherein A is Ar(CH 2 ) n - or -(CH 2 ) m -OR2, W is a single bond or cis double bond, Z is a single bond or trans double bond; m is oxo or n is 0 to 5 when Z is a single bond, or n is 1 to 5 when Z is a trans double bond; m is 2 or 3; R2 is C 1-4 alkyl; Ar is α- or #-furyl, α- or #-thienyl, α- or #-naphthyl, 3,4-dimethoxyphenyl, 3,4-methylenedioxyphenyl, 3,4,5-trimethoxyphenyl or phenyl optionally monosubstituted by halogen, trifluoromethyl, phenyl, C 1-4 alkyl or C 1-4 alkoxy; R 1 is p-biphenylyl, R is H or C 1-4 alkyl, X and Y together form a single bond or X is H and Y is alpha-hydroxy, with the proviso that when X and Y form a single bond m is oxo; and compounds of the Formulµ II, III and VI or and their C 15 epimers, wherein m is oxo or Compounds of Formula I above are obtained by esterifying the corresponding acids of Formula I in which R1 and X are hydrogen and Y is alpha-hydroxy with p-phenylphenol, and if desired, dehydrating the resulting compounds in which m is oxo and Y is alpha-hydroxy. The esters of the prostaglandin E and F series may also be obtained by hydrolysing the corresponding 11,15-bis-(tetrahydropyranyl) ethers of Formula VI above which are obtained by reacting compounds of the Formula VII with compounds of the formula and if desired, oxidizing and/or hydrogenating the resulting compounds of formula VI above in which m is Compounds of Formula II and III above are obtained by reacting compounds of formula VII above with compounds of the formula and if desired, oxidizing and/or hydrogenating the resulting compounds of Formula II above. Biphenylyl 9,15 - dioxo - 11α - hydroxy - 17- phenyl - 18,19,20 - trinor - cis - 5, trans - 13- prostadienoate is obtained by oxidizing biphenylyl 9 - oxo - 11α,15# - dihydroxy - 17- phenyl - 18,19,20 - trinor - cis - 5, trans - 13- prostadienoate with manganese dioxide. Pharmaceutical compositions, suitable for oral, intravaginal, intraamniotically, intravenous or intranasal administration, contain the above esters of Formula I together with suitable carriers or diluents. The compound possess similar pharmacological properties to those of the naturally occurring prostaglandins. Reference has been directed by the Comptroller to Specifications 1,386,146, 1,345,934 and 1,324,737.