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. [ABSTRACT FROM AUTHOR]