Prostaglandin intermediates

Abstract

Abstract A process for preparing 11-deoxyprostaglandin E1, E2 and E3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO)2PCCH2CO-(c)-CH3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH2)q wherein q is an integer from 1 to 6 or cis CH2CH=CH(CH2)r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: <IMAGE> in which R2 is hydrogen, lower alkyl or CH2OR3 wherein R3 is lower alkanoyl, R4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borehydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR6)2-(a)-(CH2)pCOOR in which R and R6 are lower alkyl, (a) is CH2CH2, cis CH=CH or CaC and p is an integer from 2 to 4, gives the corresponding cyclopentanonetriester of formula <IMAGE> or <IMAGE> in which (a), (c), p, R, R4 and R6 are as defined herein, R5 is hydrogen or tetrahydropyran-2-yl, respectively, and R7 is hydrogen or lower alkyl; the lactonized form of the cyclopentanone-triester being obtained from said alcohol derivative in which R2 is CH2OR3 wherein R3 is lower alkanoyl. In the instance when R5 is tetrahydropyran-2-yl the cyclopentanonetriester is treated with an acid to give the corresponding compound in which R5 is hydrogen. The instant compound is then treated with a base under aqueous conditions, followed by optional esterification and acylation to give the desired 11-deoxy-prostaglandin derivatives of the formula <IMAGE> in which (a), (c) and p, are as defined herein, (b) is trans CH=CH, R is hydrogen or lower alkyl, R1 is hydrogen or lower alkanoyl and R2 is hydrogen, lower alkyl or CH2OR3 wherein R3 is hydrogen or lower alkanoyl. The derivatives possess prostaglandin-like biological activity and methods for their use are gIven.

Inventors

• 👤 Nedumparambil A. Abraham
• 👤 Jehan F. Bagli
• 👤 Tibor Bogri

Bibliographic Details