Divergent total synthesis of triptolide, triptonide, tripdiolide, 16-hydroxytriptolide, and their analogues.
Divergent total synthesis of triptolide, triptonide, tripdiolide, 16-hydroxytriptolide, and their analogues.
复制标题
DOI：
10.1021/jo501744j
复制
发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Hongtao Xu;Huanyu Tang;Hui-jin Feng;Yuanchao Li
中科院分区：
文献类型：
--
作者：
Hongtao Xu;Huanyu Tang;Hui-jin Feng;Yuanchao Li
开发了一种发散路线，用于雷公藤甲素、雷公藤内酯和雷公藤二醇的正式全合成，以及16-羟基雷公藤甲素及其类似物的对映选择性形式的全合成。采用铟（III）催化的阳离子多环化反应和钯催化的羰基化-内酯形成反应作为关键步骤，简明地组装了通用高级中间体5。通过钯催化的交叉偶联或克莱森重排反应作为关键步骤，该高级中间体容易地转化为上述天然产物。此外，C13的初步结构-细胞毒活性关系研究表明，它可能是一个新的修饰位点，仍然可以保持细胞毒性。
A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate 5 was concisely assembled by employing an indium(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation-lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure-cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity.