Thiocarbonyl Ylide Chemistry Enables a Concise Synthesis of (±)-Hippolachnin A

Hippolachnin A (1) is an antifungal polyketide that bristles with ethyl groups mounted onto a caged heterotricyclic core. It has shown potent activity against Cryptococcus neoformans, a yeast that can affect immunocompromised patients as an opportunistic pathogen. Herein we describe a concise, diversifiable, and scalable synthesis of (±)-hippolachnin A (1). It features a powerful photochemical opening step, a diastereoselective addition of an ethyl cuprate and an unusual strategy to install two additional ethyl groups that makes use of a thiocarbonyl ylide generated in situ.Hippolachnin A (1)（Hippolachnin A）是一类抗真菌聚酮类化合物，其笼状杂三环核心上连有多个乙基取代基。该化合物对新生隐球菌（Cryptococcus neoformans）表现出强效活性，新生隐球菌是一种可作为机会致病菌感染免疫功能低下患者的酵母菌。本文报道了(±)-hippolachnin A (1)的简洁、可多样化修饰且可规模化的合成路线。该合成路线包含关键的高效光化学开环步骤、乙基铜试剂（ethyl cuprate）的非对映选择性加成反应，以及一种利用原位生成的硫羰基叶立德（thiocarbonyl ylide）来引入额外两个乙基的非常规策略。