Thapsigargin的全合成研究进展  

Research Progress in Total Synthesis of Thapsigargin

作　　者：彭碧 曹盼盼 康亮亮 李佳铮 阙妍炎 方引 何述钟 Peng Bi;Cao Panpan;Kang Liangliang;Li Jiazheng;Que Yanyan;Fang Yin;He Shuzhong(School of Pharmacy,Guizhou University,Guiyang,550000;Guizhou Engineering Laboratory for Synthetic Drugs,Guiyang,550025)

机构地区：[1]贵州大学药学院,贵阳550000 [2]贵州省合成药物工程实验室,贵阳550025

出　　处：《化学通报》2021年第9期888-894,共7页Chemistry

基　　金：国家自然科学基金项目(2206010324)资助。

摘　　要：Thapsigargin是一类从地中海植物毒胡萝卜(thapsia garganica)中分离得到的结构复杂的高氧化态倍半萜内酯,其对肌浆-内质网Ca2+-ATP泵(SERCAs)具有不可逆的抑制作用,抑制浓度达纳摩尔级别(KD=0.4 nmol/L)。Thapsigargin因其独特的结构和良好的生物活性而备受有机合成化学家的广泛关注。在合成中,立体选择性地构建该分子cis-5/7/5稠环体系以及多个手性中心是极具挑战性的。本文综述了该分子近二十年来的全合成研究进展。Thapsigargin is an important sesquiterpene lactone bearing highly oxidation level isolated from the mediterranean plant species Thapsia. This natural product has long been recognized as irreversible inhibitor of sarco-endoplasmic reticulum Ca2+-ATP dependent pumps(SERCAs), and the inhibitory concentration reaches the nanomolar level(KD=0.4 nmol/L). Due to its complex hexaoxygenated structure and excellent biologic activity, this molecule has attracted considerable attention from synthetic organic chemists. Stereoselective construction of a hexaoxygenated 5-7-5 tricyclic guaianolide skeleton functionalized with eight stereogenic centers presents a formidable challenge. This review summarizes the synthetic efforts towards thapsigargin in the last twenty years.

关 键 词：THAPSIGARGIN 全合成 倍半萜内酯 cis-5/7/5稠环体系 

分 类 号：TQ28[化学工程—有机化工]