Construction of the Tetracyclic Framework of Sulfur-Containing Discorhabdin-Type Alkaloids

Abstract

Herein, we report an efficient synthetic method for constructing the tetracyclic scaffold of sulfur-containing discorhabdin-type alkaloids. The key to success is the BF3•Et2O-promoted dienone-phenol-type rearrangement/sulfur insertion cascade reaction, which converts the common and readily available N,O-acetal-bridged tetracyclic framework to the labile and synthetically challenging N,S-acetal-bridged tetracyclic framework in a single step. Additionally, the hypervalent iodine promoted intramolecular oxidative dearomatization terminated with amide and indium­(III) acetate-facilitated radical cyclization were also essential elements in this study.

Total Synthesis of (+)‐Discorhabdin V**

“…As a result, unbridged discorhabdins have received the most synthetic attention. While several formal and total syntheses of achiral discorhabdin C ( 2 ) [6] and racemic discorhabdin E ( 3 ) [6c] have been reported, the numerous synthetic studies on pyrroloiminoquinones have mostly focused on preparing the tricyclic core, found in makaluvamines and related compounds, [7,8a] or forming the spirodienone [8a,9,10] . The synthesis of discorhabdin A ( 4 ) by Kita and co‐workers [11] remained the sole reported example of an asymmetric synthesis of a discorhabdin for two decades.…”