Biomimetic Enantioselective Total Synthesis of (−)-Mycoleptodiscin A

Biomimetic total synthesis of (−)-mycoleptodiscin A (1) was achieved starting from the enantiopure key intermediate, which was prepared by Friedel–Crafts reaction between 7-methoxyindole and chiral primary allylic alcohol. The crucial step in this synthesis was an intramolecular Friedel–Crafts reaction at C-4 of the indole derivative driven by the EDG/EWG within a compound that was rationally designed to prevent the cyclization reaction at the C-2 positon of indole, thereby successfully providing the complete carbon framework of 1. This intramolecular Friedel–Crafts reaction at C-4 of indole derivative could be applied for the synthesis of other C-4-substituted indole alkaloid natural products.以7-甲氧基吲哚与手性一级烯丙醇经傅-克反应（Friedel–Crafts reaction）制备得到的对映纯关键中间体为起始原料，成功完成了(-)-霉菌盘菌素A (1)的仿生全合成。该合成的关键步骤为吲哚衍生物C-4位的分子内傅-克反应，该反应由分子内的给电子基团/吸电子基团（electron-donating group/electron-withdrawing group，EDG/EWG）驱动，且通过合理设计底物以避免吲哚C-2位发生环化反应，最终成功构建出化合物1完整的碳骨架。该吲哚衍生物C-4位的分子内傅-克反应可应用于其他C-4取代吲哚生物碱类天然产物的合成。