Bioinspired Divergent Oxidative Cyclizations of Geissoschizine: Total Synthesis of (–)‐17‐nor‐Excelsinidine, (+)‐16‐epi‐Pleiocarpamine, (+)‐16‐Hydroxymethyl‐Pleiocarpamine and (+)‐Taberdivarine H - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Organic Chemistry Année : 2020

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

Résumé

We report a full account of our efforts towards bioinspired oxidative cyclizations of geissochizine and analogues 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 to the formation of the mavacurans core (N1-C16 bond). With this unified oxidative cyclization strategy: (-)-17-nor-excelsinidine, (+)-16-epi-pleiococarpamine, (+)-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 synthetized via an intramolecular nucleophilic substitution of a 7-membered ring -chlorolactame prepared from 16-desformyl-geissoschizine.

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Chimie
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hal-02960543 , version 1 (12-11-2020)

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Maxime Jarret, Aurélien Tap, Victor Turpin, Natacha Denizot, Cyrille Kouklovsky, et al.. Bioinspired Divergent Oxidative Cyclizations of Geissoschizine: Total Synthesis of (–)‐17‐nor‐Excelsinidine, (+)‐16‐epi‐Pleiocarpamine, (+)‐16‐Hydroxymethyl‐Pleiocarpamine and (+)‐Taberdivarine H. European Journal of Organic Chemistry, 2020, 40, pp.6340-6351. ⟨10.1002/ejoc.202000962⟩. ⟨hal-02960543⟩
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