Studies in biomimetic alkaloid syntheses. 7. Stereospecific total syntheses of ibophyllidine and 20-epiibophyllidine

Abstract

The alkaloids ibophyllidine (1) and 20-epiibophyllidine (2) were selectively synthesized by utilizing reaction pathways which pass respectively either through a biomimetic ring D-seco intermediate, 8, or through a norsecodine intermediate, 13.

Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)‐Catalyzed Generation of Reactive Enamine Intermediates

“…Finally, the versatility of our synthetic strategy was further demonstrated by expanding its scope towards the synthesis of enantiomerically pure monoterpene indole alkaloid, (+)‐20‐ epi ‐ibophyllidine,,, beginning with the γ‐lactam derivative ( S )‐5‐ethylpyrrolidin‐2‐one, 23 (Scheme ). Thus, 23 was converted into the stable lactam intermediate 29 by similar synthetic steps to those described in Scheme (see the Supporting Information for details).…”

Construction of Hexahydropyrido[3,2‐c]carbazole and Hexahydropyrrolo[3,2‐c]carbazole Skeletons for the Synthesis of Related Indole Alkaloids

“…Ibophyllidine ( 2a ) and deethylibophyllidine ( 2b ) (Scheme ), which are monoterpenoid indole alkaloids, have been the primary target molecules, and only a few creative and useful synthetic strategies have been developed . In the synthetic approaches, the [ ABDE ]‐type tetracyclic structures, so‐called octahydropyrrolo[3,2‐ c ]carbazole, are very important precursors and have been synthesized successfully as a core structure of ibophyllidine alkaloids .…”

Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation

“…Cyclization was found, however, to occur via the diene approaching opposite the C20 ethyl substituent, generating 20- epi -ibophyllidine ( 4 ) exclusively. 4,5 In an alternative strategy, the Bonjoch group attempted a key Fischer indolization on a bicyclic ketone bearing all of the D ring stereochemistry ( 5 → 6 + 6′ ), but obtained poor selectivity (ratio of 6 : 6′ = 1:4.5). 6 In fact, the four reported total syntheses of ibophyllidine have all been accomplished utilizing a singular tactical blueprint based on a variation of Kuehne’s original Diels–Alder strategy.…”

“…First disclosed by Kuehne and Bohnert, this approach generated the desired A-B-C-E ring system, but required full epimerization at C3 and C7 in order to access ibophyllidine (7a / 8a; Scheme 1). 4 In a similar approach developed during a study aimed at advancing a common intermediate to a number of related aspidosperma alkaloids, the synthesis still required epimerization of the C3 and C7 centers and, in this case, also necessitated excision of the additional carbon atom that was positioned to allow access to other targets (7c / 8c). 7 In 2007, Kalaus et al reported a similar tactic nearly paralleling Kuehne and Bohnert's studies that necessitated inversion of stereochemistry at C3 after formation of the C and E rings (7d / 8d).…”