Total Syntheses of Dihydroindole <i>Aspidosperma</i> Alkaloids: Reductive Interrupted Fischer Indolization Followed by Redox Diversification

We report a novel reductive interrupted Fischer indolization process for the concise assembly of the 20-oxoaspidospermidine framework. This rapid complexity generating route paves the way toward various dihydroindole Aspidosperma alkaloids with different C-5 side chain redox patterns. The end-game redox modulations were accomplished by modified Wolff–Kishner reaction and photo-Wolff rearrangement, enabling the total synthesis of (−)-aspidospermidine, (−)-limaspermidine, and (+)-17-demethoxy-N-acetylcylindrocarine and the formal total synthesis of (−)-1-acetylaspidoalbidine.本研究报道了一种全新的还原中断式费歇尔吲哚合成（reductive interrupted Fischer indolization）方法，用于简洁构建20-氧代白坚木精（20-oxoaspidospermidine）骨架。该快速构建分子复杂度的合成路径，为制备一系列带有不同C-5侧链氧化还原模式的二氢吲哚型白坚木属（Aspidosperma）生物碱开辟了可行途径。本研究通过改良沃尔夫-凯惜纳反应（modified Wolff–Kishner reaction）与光促沃尔夫重排（photo-Wolff rearrangement）实现了终阶段的氧化还原调控，成功完成了(-)-白坚木精（aspidospermidine）、(-)-利萨帕明德碱（limaspermidine）以及(+)-17-去甲氧基-N-乙酰圆柱林碱（17-demethoxy-N-acetylcylindrocarine）的全合成，并实现了(-)-1-乙酰白坚木阿比定（1-acetylaspidoalbidine）的形式全合成。