Hicks EF,
Inoue K,
Stoltz BM.
*
California Institute of Technology, Pasadena, USA
Enantioselective Total Synthesis of (–)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy.
J. Am. Chem. Soc. 2024;
146: 4340-4345
DOI:
10.1021/jacs.3c13590
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.
