Department of Chemistry, University of California, 1102 Natural Science II, Irvine, California 92697-2025, United States.
Department of Pharmaceutical Sciences, University of California, 101 Theory, Suite 101, Irvine, California 92697-3958, United States.
J Org Chem. 2022 Jan 21;87(2):1398-1420. doi: 10.1021/acs.joc.1c02700. Epub 2022 Jan 6.
A full account of the development of a concise and highly stereoselective synthesis of (+)-7,20-diisocyanoadociane (DICA)─a structurally complex isocyanoditerpene with potent antiplasmodial activity─is described. The strategy that evolved relies on the rapid construction of unsaturated tricyclic precursors designed to undergo stereocontrolled Birch reductions and a subsequent "bay ring" formation to generate the isocycloamphilectane core. This report is divided into three sections: (1) a description of the initial strategy and the results that focused our efforts on a single route to the DICA core, (2) a discussion of the precise choreography needed to enable a first-generation formal synthesis of (±)-DICA, and (3) the execution of a 13-step second-generation synthesis of (+)-DICA that builds on important lessons learned from the first-generation effort.
本文详细描述了（+）-7,20-二异氰基adociane（DICA）的简洁、高度对映选择性合成方法的发展。DICA 是一种具有潜在抗疟活性的结构复杂的异氰二萜，该策略依赖于不饱和三环前体的快速构建，这些前体旨在进行立体控制的 Birch 还原反应，然后进行“海湾环”形成，从而生成异环氨菲烷核心。本报告分为三个部分：（1）描述初始策略和结果，重点介绍了通往 DICA 核心的单一途径；（2）讨论实现（±）-DICA 第一代全合成所需的精确编排；（3）执行基于第一代研究经验的 13 步（+）-DICA 第二代合成。
