Prostratin, a highly complex diterpene natural product, is a pre-clinical candidate in developing a cure for HIV-1 infection and also a potent and selective inhibitor of several tumors. Despite nearly 40 years of progress, prostratin and related natural products still present formidable challenges for synthetic chemists. Here, we report a total synthesis of (±)-prostratin that proceeds in 23 steps from cyclopentadiene. The synthetic strategy includes rapid assembly of the tricyclic core and highly controlled establishment of the densely functionalized C ring, featuring an array of stereoselective transformations including alkoxide-guided 1,4-additions and cyclopropane formation. This work should enable further explorations of chemical and biological spaces based on prostratin and related natural products.

Prostratin是一种高度复杂的二萜天然产物，是开发可治愈HIV-1感染的临床前候选药物，也是多种肿瘤的有效和选择性抑制剂。尽管有近40年的发展，但prostratin及其相关天然产物仍对合成化学家提出了严峻的挑战。在这里，我们报告了从环戊二烯进行23个步骤的（±）-prostratin的总合成。合成策略包括快速组装三环核和高度受控地建立致密官能化的C环，其特征在于一系列立体选择性转化，包括醇盐引导的1,4-加成和环丙烷的形成。这项工作应使能够进一步研究基于prostratin和相关天然产物的化学和生物空间。