Total Syntheses of Kopsaporine, Kopsinol and Kopsiloscine A

Abstract

Kopsia alkaloids represent a complex class of natural products bearing a polycyclic ring system with two or three consecutive quaternary carbon centers. In this article, we report the first total synthesis of Kopsaporine related alkaloids. Features of our structure‐unit‐based strategy are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza‐Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an olefin migration vinylogous alkylation to establish the C20 all‐carbon quaternary center, an iridium complex mediated radical addition to fuse the aspidofractine framework, an unprecedented IBX oxidation to introduce the α‐hydroxyketone moiety, and a bioinspired retro‐Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A.

The Total Synthesis of Aspidofractinine and Related Alkaloids

“…[47] 2.14. Zhang and Chen's total syntheses of kopsaporinerelated indole alkaloids [49] Very recently, Zhang and Chen's group reported the first total syntheses of kopsaporine 8, kopsinol 9, and kopsiloscine A 10 (Scheme 15). [49] These aspidofractinine-like alkaloids with potent biological activities were isolated from Kopsia singapurensis and Kopsia teoi.…”

“…Zhang and Chen's total syntheses of kopsaporinerelated indole alkaloids [49] Very recently, Zhang and Chen's group reported the first total syntheses of kopsaporine 8, kopsinol 9, and kopsiloscine A 10 (Scheme 15). [49] These aspidofractinine-like alkaloids with potent biological activities were isolated from Kopsia singapurensis and Kopsia teoi. [50,51] A cascade intramolecular Pummerer rearrangement-induced nucleophilic cyclization/aza-Prins cyclization was developed to construct the highly functional hexahydrocarbazole skeleton, and the C-20 all-carbon quaternary center was introduced through an olefin migration vinylogous alkylation.…”

“…Zhang and Chen's total syntheses of kopsaporine, kopsinol, and kopsiloscine A. [49] acid 267 in the presence of HATU and DIPEA gave amide 268 in 78 % yield (dr 1 : 1). Inspired by Bonjoch's conditions, [52] Zhang and Chen group optimized the first cascade Pummerer rearrangement induced nucleophilic addition/aza-Prins cyclization to furnish the hexahydro-1H-pyrrolo[2,3-d] carbazol-2(3H)one structure units.…”