近日，中国科学院上海有机化学研究所桂敬汉团队研究了重排Swinhoeisterols A-C的发散性全合成。2025年6月2日，《美国化学会杂志》发表了这一成果。

Swinhoeisterols A-C分别为13（14→8），14(8→7)-diabeto类固醇具有有趣的6/6/5/7四环核心结构，对组蛋白乙酰转移酶p300具有强效抑制活性。

研究组报告了它们从现成的（S）-维兰德-米舍尔酮到不同的全合成方法。开发了氯酚三氟甲磺酸酯的串联根岸/Heck交叉偶联，使用甲硅烷基连接的高烯丙基锌试剂安装不稳定的亚甲基环戊烯基序，该试剂经过精心设计，可抑制不希望的[Pd]-H插入。此外，二烯（一种很少使用的自由基供体）与系留丙烯腈基团的Baran还原性烯烃偶联允许同时构建七元环和两个连续的立体中心，包括一个季碳中心。

附：英文原文

Title: Divergent Total Syntheses of Rearranged Steroids Swinhoeisterols A–C

Author: Ganlin Huang, Xinliang Zhang, Yu-Cheng Gu, Jinghan Gui

Issue&Volume: June 2, 2025

Abstract: Swinhoeisterols A–C are 13(14→8),14(8→7)-diabeo-steroids possessing an intriguing 6/6/5/7 tetracyclic core framework and potent inhibitory activity against the histone acetyltransferase p300. Herein we report their divergent total syntheses from readily available (S)-Wieland–Miescher ketone. A tandem Negishi/Heck cross-coupling of a chloroenol triflate was developed to install the labile methylenecyclopentene motif using a silyl-tethered homoallylic zinc reagent that was carefully designed to suppress undesired [Pd]–H insertion. Furthermore, a Baran reductive olefin coupling of a diene, a rarely used radical donor, with a tethered acrylonitrile group allowed for the simultaneous construction of the seven-membered ring and two contiguous stereocenters, including a quaternary carbon center.

DOI: 10.1021/jacs.5c07053

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c07053