Chemistry of the Ginkgolides, V. On the Preparation of the Ginkgolide Skeleton

Abstract

Abstract 3,14‐Didehydro‐10‐hydroxyginkgolide On the nomenclature: The skeleton of the ginkgolides A, B, C, M and J with the natural configuration is called “ginkgolide” since the systematic IUPAC nomenclature is too complicated. According to our nomenclature ginkgolide “A” is 3,10‐dihydroxyginkgolide, ginkgolide “B” is 1,3,10‐trihydroxyginkgolide etc. The numbering of the C atoms (formula 1 ) and the indexing of the H atoms (formula 2 ) are those proposed by Nakanishi [2] . ( 1 ) was prepared by reaction of 3,10‐dihydroxyginkgolide ( 3 ) (ginkgolide “A”) by reaction with phosphoryl chloride in pyridine. Catalytic hydrogenation of 1 leads to 10‐hydroxy‐14‐epiginkgolide ( 2a ), which was epimerized with 4‐(dimethylamino)pyridine (DMAP) in acetonitrile to give 10‐hydroxyginkgolide ( 3a ). 14‐Epiginkgolide ( 2d ) and ginkgolide ( 3d ) were obtained from 2a and 3a via the 10‐ O ‐phenylthiocarbonyl derivatives 2c and 3c by means of a free‐radical reduction with tri‐ n ‐butyltin hydride/α,α′‐azobis(isobutyronitrile) (AIBN). By heating the 14‐epiginkgolides 2a and 2b and the ginkgolides 3a and 3b in acetonitrile with DMAP an equilibrium on the side of the ginkgolides was established. The constitution and configuration of the compounds were proven by their 1 H‐ and 13 C‐NMR spectra.