环氧型taccalonolides的全合成研究

Taccalonolides是一类具有微管稳定作用的复杂天然产物。研究发现，C22-C23环氧型的taccalonolide可以与微管蛋白形成共价结合从而表现出良好的抗肿瘤活性，这类化合物对一部分紫杉醇耐药的肿瘤仍有较好的抑制作用。在结构上，taccalonolides家族的天然产物都具有一个高度氧化的6环骨架和20个左右的手性中心，对化学合成形成了极大的挑战。目前尚未有taccalonolide的全合成报导。本项目设计了一条汇聚式的合成路线，通过将复杂的天然产物骨架分为大小相等的两个片段，希望能在20步左右完成taccalonolide AF及taccalonolide AI-epoxide的全合成。本项目的成功将为这类结构复杂的微管稳定剂实现化学合成上的突破，并为后续的生物学研究及药学应用打下基础。

Taccalonolides represent a family of natural products with significant microtubule-stabilizing effect. The C22-C23 epoxide-taccalonolides can covalently interact with microtubules to exhibit extraordinary anti-tumor activities even towards tumor cells with paclitaxel resistance. Structurally, these natural products share a highly oxygenated polycyclic skeleton with 20 contiguous stereocenters. Due to the great synthetic challenge provided by the structural complexity, no total synthesis of taccalonolides has been reported. In this project, a convergent synthetic strategy with 20 steps in total was designed for taccalonolide AF and taccalonolide AI-epoxide. The success of this project will provide a breakthrough in the research area of microtubule-stabilizing agents.