雷公藤中的雷公藤内酯醇具有抗肿瘤、免疫抑制等多种生物活性，但是副作用大等特点限制了临床的使用。为了获得高效低毒的雷公藤内酯醇衍生物，对其结构进行了改造。近5年来对雷公藤内酯醇的结构改造又有了新进展，包括对其14位羟基、不饱和五元内酯环、B环、13位异丙基和10位甲基的结构改造，得到一系列衍生物。其中对14位羟基进行前药设计，从而降低了雷公藤内酯醇的毒性，14位羟基改造为α-羟基衍生物后发现了与雷公藤内酯醇活性相当的衍生物。综述了近5年来对雷公藤内酯醇的结构改造及构效关系研究进展。

Triptolide, an ingredient of Tripterygium wilfordii, has been demonstrated to possess many biological activities such as immunosuppressive activity, antitumor activity and so on. However due to its severe toxicity, triptolide limited its clinical use. To obtain derivatives with high efficacy and low toxicity, structural modifications were conducted. A new progress was made on triptolide structural modifications in recent five years, including C-14-hydroxyl group, the lactone ring, B ring, C-13 isopropyl group and C-10 methyl group modified derivatives, and a series of derivatives were obtained. C-14-hydroxyl prodrug design reduced the toxicity of triptolide; An epi-tripolide derivative by introducing of the indazole aminomethyl group showed comparable potency with triptolide. This review will focus on structural modification and structure-activity relationship of triptolide in recent five years.

福建省自然科学基金资助项目（2017J01141）；福建省省属公益类科研院所基本科研专项（2015R1031-1）