Biomimetic Total Syntheses of Borreverine and Flinderole Alkaloids

Dimeric indole alkaloids represent a structurally unique class of natural products having interesting biological activities. Recently, we reported the first total synthesis of flinderoles B and C, structurally unique and potent antimalarial natural products. Central to the design of the approach and by virtue of a one-pot, acid-catalyzed dimerization reaction, the route also provided total synthesis of the borreverine class of natural products. This full account details the progress of efforts that culminated in the protecting-group-free, six-step total synthesis of all of the flindersia alkaloids: dimethylisoborreverine, isoborreverine, flinderoles A–C, and their analogues. A biomimetic approach featuring a scalable and catalytic formal [3 + 2] cycloaddition and Diels–Alder reaction is outlined in detail. On the basis of the experimental observations, a detailed mechanism has been proposed for the dimerization of tertiary alcohol 28.二聚吲哚生物碱（dimeric indole alkaloids）是一类结构独特的天然产物，具有引人关注的生物活性。近期，我们首次报道了弗林德罗勒B与C（flinderoles B and C）的全合成——二者均为结构独特且强效的抗疟天然产物。该合成路线的设计核心在于一锅法酸催化二聚反应，借此途径同时实现了波瑞维林类（borreverine）天然产物的全合成。本完整研究详述了相关工作的进展：最终实现了无保护基、六步完成所有弗林德西亚生物碱（flindersia alkaloids）——包括二甲基异波瑞维林、异波瑞维林、弗林德罗勒A~C及其类似物——的全合成。本文详细介绍了一种仿生合成策略，其核心为可规模化且催化的形式[3+2]环加成（formal [3 + 2] cycloaddition）与狄尔斯-阿尔德（Diels-Alder）反应。基于实验观测结果，我们针对叔醇28（tertiary alcohol 28）的二聚反应提出了详尽的反应机理。