Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Total Synthesis of (-)-17-nor-Excelsinidine

Abstract

We report the first total synthesis of (-)-17-nor-excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4-C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium-acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution on a 16-chlorolactam with the N4 nitrogen atom or a direct I₂ -mediated N4-C16 oxidative coupling from the enolate of geissoschizine.

Keywords: alkaloids; biosynthesis; excelsinidine; geissoschizine; oxidative coupling.