Thapsigargin的全合成研究进展

Research Progress in Total Synthesis of Thapsigargin

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.