Department of Chemistry & Biochemistry , Baylor University , Waco , Texas 76710 , United States.
Department of Pharmacology and Molecular Sciences , John Hopkins School of Medicine , 725 North Wolfe Street , Baltimore , Maryland 21205 , United States.
Org Lett. 2019 Sep 20;21(18):7394-7399. doi: 10.1021/acs.orglett.9b02713. Epub 2019 Sep 9.
A pharmacophore-directed retrosynthesis strategy applied to rameswaralide provided simplified precursors bearing the common 5,5,6 (red) and 5,5,7 (blue) skeleton present in several cembranoid and norcembranoids from soft corals. Key steps include a Diels-Alder lactonization organocascade delivering the common 5,5,6 core and a subsequent ring expansion affording a 5,5,7 core serviceable for the synthesis of rameswaralide. Initial structure-activity relationships of intermediates en route to the natural product have revealed interesting differential and selective cytotoxicity.
基于药效团的逆合成分析策略应用于 rameswaralide，提供了简化的前体，这些前体具有几种软珊瑚来源的cembranoid 和 norcembranoids 中共同的 5,5,6（红色）和 5,5,7（蓝色）骨架。关键步骤包括 Diels-Alder 内酯化有机级联反应，提供共同的 5,5,6 核心，以及随后的环扩张，提供可用于 rameswaralide 合成的 5,5,7 核心。在通往天然产物的中间体的初始结构-活性关系研究中，揭示了有趣的差异和选择性细胞毒性。
