Wortmannin（渥曼青霉素）是一个具有广谱生物活性的甾体代谢物，在细胞生物学中具有重要应用价值。由于该分子极具挑战的分子结构，自分离迄今60年来缺乏高效的合成路线。本项目拟发展一种以氢转移反应启动的烯烃交叉偶联以及分子内傅克酰基化为关键步骤的汇聚式合成路线，有望从商品化的试剂经由十步左右的转化完成wortmannin的全合成。在此基础上，我们将制备它的新颖类似物，进行深入的构效关系研究，希望能找到具有更好的代谢稳定性和更小细胞毒性的先导化合物，为wortmannin类新药研发创造条件。

Wortmanin is a steroid metabolite with a broad spectrum of biological activities, which has important applications in cell biology. Because of its challenging molecular structure, there’s still lack of highly efficient total synthesis of wortmannin in the past 60 years since its isolation. The proposal aims at developing a convergent synthesis of wortmanin featuring hydrogen atom transfer (HAT) initiated alkenes cross coupling and intramolecular Friedel-Crafts acylation, which will finish the synthesis in about ten steps with commercial available reagents as starting materials. Based on the designed synthesis, we will be able to synthesize some novel analogs of wortmannin to conduct intensive SAR study. Hopefully, a lead compound with better metabolic stability and less toxicity will be found, which will lay solid foundation for the new drug discovery.