灰安毒素III向10-表灰安毒素III的转化。其X射线晶体学分析及对小鼠的急性毒性

Transformation of grayanotoxin III to 10-epi-grayanotoxin III. Its X-ray crystallographic analysis and acute toxicity in mice.

作者信息

Terai T, Sato M, Narama I, Matuura T, Katakawa J, Tetsumi M

机构信息

Department of Applied Chemistry, Osaka Institute of Technology, Osaka, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1996 Jun;44(6):1245-7. doi: 10.1248/cpb.44.1245.

DOI:10.1248/cpb.44.1245

PMID:8814955

Abstract

Grayanotoxin (GTX) III, a tetracyclic diterpenoid, is the main toxic component obtained from the leaves of Leucothoe grayana 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 derivation 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.

摘要

灰藜毒素（GTX）III是一种四环二萜类化合物，是从灰叶白珠（Leucothoe grayana MAX）的叶子中提取的主要有毒成分。在本文中，我们报告了GTX-III的毒性与C10立体结构之间的相关性。10-表-GTX-III由GTX-III经四步反应制得。在氯仿中用甲酸/过氧化氢氧化GTX-II-3,6,14,16-四乙酸酯，高产率得到10,20-环氧衍生物。在四氢呋喃中用LiAlH4还原10,20-环氧乙酸酯，得到两种产物，10-表-GTX-III和10,20-环氧-GTX-II。通过X射线晶体学分析结果推导了10-表-GTX-III的绝对结构。估计10-表-GTX-III对小鼠的急性毒性剂量水平约为天然GTX-III的一半。