Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, Irvine, CA, 92697-2025, USA.
Angew Chem Int Ed Engl. 2016 Jun 13;55(25):7180-3. doi: 10.1002/anie.201603581. Epub 2016 May 10.
7,20-Diisocyanoadociane (DICA) is a potent antimalarial isocyanoterpene endowed with a fascinating tetracyclic structure composed of fused chair cyclohexanes. We report a highly stereocontrolled synthesis of a late-stage intermediate, the "Corey dione", from which DICA has been made previously. This formal synthesis features a rapid buildup of much of the complexity of the target through a sequence of enone tandem vicinal difunctionalization, Friedel-Crafts cyclodehydration, and sequential stereocontrolled reductions. Most importantly, this success establishes the broader feasibility of our previously developed general synthesis approach to the isocyanoterpene family and provides a blueprint for a very direct synthesis of DICA and related natural products.
7,20-二异氰基莰烷（DICA）是一种有效的抗疟异氰萜类化合物，具有迷人的四环结构，由融合的椅式环己烷组成。我们报告了一种高度立体控制的合成晚期中间体“Corey 二酮”的方法，以前曾用该中间体合成 DICA。该形式合成通过一系列烯酮串联邻位双官能化、傅-克环脱水和连续立体控制还原，快速构建了目标物的大部分复杂性。最重要的是，这一成功确立了我们之前开发的异氰萜类化合物通用合成方法的更广泛可行性，并为 DICA 和相关天然产物的非常直接的合成提供了蓝图。
