Bioinspired Divergent Oxidative Cyclizations of Geissoschizine: Total Synthesis of (–)‐17‐nor‐Excelsinidine, (+)‐16‐epi‐Pleiocarpamine, (+)‐16‐Hydroxymethyl‐Pleiocarpamine and (+)‐Taberdivarine H

Abstract

We report a full account of our efforts towards bioinspired oxidative cyclizations of geissochizine and analogs to mimic the biosynthesis of the mavacuran, akuammilan, and excelsinidine groups of monoterpene indole alkaloids. The construction of the A,B,C,D ring system of geissoschizine was first achieved by merging two known syntheses of this alkaloid. Modified Ma's oxidative conditions (KHMDS/I2) applied directly to geissoschizine induced formation of the N4–C16 bond encountered in the excelsinidines core. Identical conditions applied to C16‐dimethylmalonate‐containing N4‐quaternized substrates ended in the formation of the mavacurans core (N1–C16 bond). With this unified oxidative cyclization strategy: (–)‐17‐nor‐excelsinidine, (+)‐16‐epi‐pleiocarpamine, (+)‐16‐hydroxymethyl‐pleiocarpamine, 16‐formyl‐pleiocarpamine and (+)‐taberdivarine H were synthetized. We also report a shortened total synthesis of 16‐epi‐pleiocarpamine compared to our preliminary communication from a C16‐monoester analog. Alternatively, 17‐nor‐excelsinidine was synthesized via an intramolecular nucleophilic substitution of a 7‐membered ring α‐chlorolactam prepared from 16‐desformyl‐geissoschizine.