Synthesis of 11-deoxyprostaglandins

Abstract

Abstract Improved procedures and intermediates for synthesizing 11-deoxyprostaglandins wherein trans-2,3-dicarbomethoxycyclopentanone is subjected to a novel alcoholysis with β,β,β-trichloroethanol to substitute a β,β,62 -trichlorocarboethoxy group at the 2-position followed by alkylation to allow for a wide range of upper side chains to be introduced at the 2-position of the cyclopentanone ring. The unwanted β,β,β-trichlorocarboethoxy group at the 2-position can then be removed easily by a zinc induced elimination-decarboxylation sequence. Base catalyzed epimerization of the 2-position side chain to the desired trans-configuration, relative to the carbomethoxy group in the 3-position, is followed by partial reduction of the 2-hexynyl moiety of the side chain to the desired cis-olefinic group of the E 2 -type 11-dioxyprostaglandins, or through total reduction to the alkane upper side chain of E 1 -type-prostaglandin analogs. Modification thereafter of the carbonyl group at the 3-position of the cyclopentanone ring by a variety of reagents allows introduction of the lower side chain present in the prostaglandins themselves or a variety of other side chains derived from the 3-carboxy-, 3-hydroxymethyl- or 3-aldehyde-substituted cyclopentanone ring. From the latter, 11-deoxyprostaglandins can be prepared by known procedures.

Inventors

• 👤 William L. White
• 👤 Peter B. Anzeveno

Bibliographic Details