Iboga natural products comprise a large family of monoterpene indole alkaloids, with more than 100 molecules have been reported to date. The intriguing structures featuring an indole, a seven-membered tetrahydroazepine, and a bicyclic isoquinuclidine together with their important biological activities such as anti-neuritis and anti-tumor have triggered particular interest from the organic synthetic community. Here, we present the synthetic study on Iboga alkaloids 3(S)-Cyanoisovoacangine and 3(S)-Cyanovoacangine. As shown in the figure. The chiral aza[3.3.1] bridged cycle in 3 was established through an efficient asymmetric phase-transfer-catalyzed Michael/aldol cascade reaction involving cyano-containing tryptamine derivative 1 with 2-ethylacrole 2, and a full-carbon quaternary chiral center at C16 position was assembled. Bridged cycle 3 was transformed into allyl alcohol 4 via multi-step functionality manipulation. 5 was synthesized from 4 through the opening of lactam at C3, following an intramolecular aza Michael reaction for installing a challenging aza seven-membered cycle in intermediate 6 with three adjacent chiral centers. Aza[2.2.2] bridged ring in Iboga alkaloid 7 could be constructed by lactam of seven-membered cycle 6. The key to the strategy is that [3.3.3] bridged skeleton is converted into [2.2.2] bridged cycle through lactam ring opening.

Synthesis of 3 (S)-cyanoisovoacangine and 3 (S)-cyanovoacangine

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.