Enantioselective Total Synthesis of (+)-Gliocladine C: Convergent Construction of Cyclotryptamine-Fused Polyoxopiperazines and a General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors

A concise second-generation total synthesis of the fungal-derived alkaloid (+)-gliocladin C (11) in 10 steps and 11% overall yield from isatin is reported. In addition, the epipolythiodioxopiperazine (ETP) natural product (+)-gliocladine C (6) has been prepared in six steps and 29% yield from the di-(tert-butoxycarbonyl) precursor of 11. The total synthesis of 6 constitutes the first total synthesis of an ETP natural product containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter in the pyrrolidine ring.

本文报道了以靛红为起始原料，经10步反应、总收率11%，完成真菌来源生物碱(+)-gliocladin C（11）的简洁第二代全合成。此外，本研究以化合物11的二叔丁氧羰基（di-(tert-butoxycarbonyl)）前体为原料，经6步反应、总收率29%，完成了表硫代二氧哌嗪（epipolythiodioxopiperazine, ETP）类天然产物(+)-gliocladine C（6）的全合成。(+)-gliocladine C（6）的全合成，首次实现了吡咯烷环内季碳立体中心邻位带有羟基取代基的ETP类天然产物的全合成。