埃博霉素
化学
立体选择性
羟醛反应
维蒂希反应
全合成
立体化学
腙
基质(水族馆)
组合化学
有机化学
催化作用
海洋学
地质学
作者
K. C. Nicolaou,Sacha Ninkovic,Francisco Sarabia,Dionisios Vourloumis,Yan He,Hans Vallberg,M. Ray V. Finlay,Zhen Yang
摘要
The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9−12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization of intermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.
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