Transforamtion of Grayanotoxin III to 10-epi-Grayanotoxin III. Its X-Ray Crystallographic Analysis and Acute Toxicity in Mice

Abstract

Grayanotoxin(GTX) III, a tetracyclic diterpenoid, is the main toxic component obtained from the leaves of Leucothoe grayama MAX. In this paper, we report the correlation between toxicity and C₁₀ stereostructure of GTX-III. 10-epi-GTX-III was derived from GTX-III in four steps. Oxidation of the GTX-II-3, 6, 14, 16-tetraacetate with formic acid/hydrogen peroxide in chloroform gave 10, 20-epoxy derivative in high yield. Reduction of the 10, 20-epoxyacetate with LiAlH₄ in tetrahydrofuran gave the two products, 10-epi-GTX-III and 10, 20-epoxy-GTX-II. The absolute structure of the 10-epi-GTX-III was deduced from the results of X-ray crystallographic analysis. Dosage level of acute toxicity of 10-epi-GTX, III in mice was estimated at about half of natural GTX-III.