John E. Pike

NOVEL PROSTAGLANDIN SYNTHESES

Syntheses of 2 different classes of prostaglandin (PG) analogs are described that of the 3-oxa-PGs and that of the 15-methyl PGs the former of which inhibit beta-oxidative degradation and the latter of which prevent degradation by the C-15 dehydrogenase. 7 sterochemical figures accompany the descriptions of the synthesis procedures. The analogs though inert to 2 of the recognized modes of enzymatic catabolism maintain appreciable smooth muscle activity. Furthermore as an alternative to totally synthetic routes a partially synthetic route by which the 15-methyl analogs of PGE and PGF types as well as the partially synthetic route by which the types as well as the parent PGs may be derived from the non-mammalian marine source Plexaura Homomall is described.

A new approach to 16α-halo corticoids. I. The synthesis of 16-hydroxy steroids

Abstract Reaction of cis -17(20)-pregnen-21-oic acid methyl esters with selenium dioxide gives two 16-hydroxy steroids, a 16α-hydroxy- cis -unsaturated ester and a 16β-hydroxy- trans derivative. Reaction of the trans isomer produces mainly the 16α-hydroxy trans derivative. The application of the hydroxylation reaction to a variety of steroids is described. The stereochemical significance of these findings is discussed as well as the intended use of these 16-hydroxy steroids as intermediates for the synthesis of 16α-halo-corticoids.

A total synthesis of (±)-prostaglandin E3 methyl ester via endo-bicyclohexane intermediates

(±)-Prostaglandin E3 methyl ester has been synthesized via endo-bicyclohexane intermediates.

A new approach to 16α-halo corticoids. II The synthesis of 16α-fluoro and 16α-chloro corticoids

Abstract Reaction of 16-hydroxy-17(20)-pregnen-21-oic acid methyl esters with N-(2-chloro-1,1,2-tri-fluorethyl)-diethylamine gives in high yield the corresponding 16-fluoro unsaturated esters, inversion accompanying the replacement at C-16. In a similar manner the 16-chloro-17(20)-pregnen-21-oic acid methyl esters are readily prepared in excellent yields using N,N-diethyl-1,2,2-trichlorovinylamine. Reduction of the 16α-fluoro derivatives with lithium aluminum hydride leads to the 16α-fluoro-17(20)-pregnene-21-hydroxy compounds, which on treatment (as the 21-acetates) with osmium tetroxide and Nmethylmorpholine oxide-hydrogen peroxide complex lead to the 16α-fluoro steroids with the cortical side chain. A similar reaction sequence is applicable to the 16α-chloro series except that it is necessary to reduce the unsaturated esters with diisobutyl aluminum hydride (Dibal-H) to avoid reductive removal of the 16α-chlorine substituent.

The Total Synthesis of Prostaglandins

Prostaglandins, a family of naturally occurring hydroxy fatty acids found widely distributed in mammalian tissues, have been found to have a wide potential in medical use. The need to synthesize these substances for study, first, and, later, for production and distribution prompted this review of the various methods for chemical synthesis of these compounds. Following a general introduction, this review presents 6 major chapters: 1) the structure and chemical transformations of prostaglandins; 2) general approaches to prostaglandin synthesis (these include initial Corey synthesis of dl-PGE1, Coreys second synthesis of dl-PGE1, a stereocontrolled synthesis of PGE2 and F2 alpha, also by Coreys methods, bicyclohexane route to prostaglandins, and nonenzyme cyclization of fatty acids), 3) synthetic routes to structurally simplified prostaglandins (synthesis of dl-13,14-dihydro-PGE1 ethyl ester, synthesis of dl-15-dehydro-PGE1, and synthesis of dl-PGB1); 4) synthetic routes to prostaglandin analogs (11-deoxy-prostaglandins and 7-oxa-prostaglandins); 5) miscellaneous synthetic approaches; and 6) resolution of racemic prostaglandins.