Total Synthesis of (–)-Hunterine A

Key words

(–)-hunterine A - rearranged monoterpene indole alkaloid - Noyori transfer hydrogenation - aza-Cope/Mannich reaction - azide-alkene dipolar cycloaddition

Significance

Stoltz and co-workers present the first total synthesis of (–)-hunterine A. This rearranged monoterpene indole alkaloid was isolated in 2019 and features a pentacyclic core structure. The synthesis hinges on a desymmetrization, an aza-Cope/Mannich sequence, and an azide-alkene dipolar cycloaddition.

Comment

Desymmetrization of diketone A was achieved through Noyori transfer hydrogenation, furnishing ketone C. Upon treatment with silver(I) nitrate in ethanol, allylic alcohol G underwent an aza-Cope/Mannich sequence, giving rise to ketone I, which is the substrate for an azide–alkene dipolar cycloaddition. Triazoline J was transformed to (–)-hunterine A through irradiation, opening of the resulting putative aziridine with acetic acid, and ­hydrolysis.

Publication History

Article published online:
15 April 2024