Conformational Analysis of Prostaglandins. II. Most Probable Conformation of Prostaglandin A, B, E, and F

Abstract

The computer experiments were carried out on the physiologically active compounds of prostaglandins : PGE₁, 15-epi PGE₁, 11-epi PGE₁, 11, 15-epi PGE₁, PGA₁, 15-epi PGA₁, PGF_1α, PGF_1β, and PGB₁. Sterically allowed conformations and their conformational energies were calculated, and correlation between the conformation and biological potencies of the prostaglandins was examined. The pair of isomers, PGE₁ and 15-epi PGE₁, has equal number of sterically allowed conformations and similar range of conformational energies, but the distribution of conformational energies and the conformation near the five-membered ring are quite different. Data on 11-epi PGE₁, and 11, 15-epi PGE₁ or PGA₁ and 15-epi PGA₁ were also in the same pattern. The conformation near the five-membered ring are restricted except in PGB₁. Orientation of the hydroxyl group bonded to C₁₅ affects orientation of the side chain of prostaglandins. Importance of the orientation of the hydroxyl group and of the conformation near the five-membered ring was suggested.