A general approach to 2,2-disubstituted indoxyls: total synthesis of brevianamide A and trigonoliimine C.

ABSTRACT: The indoxyl unit is a common structural motif in alkaloid natural products and bioactive compounds. Here, we report a general method that transforms readily available 2-substituted indoles into 2,2-disubstituted indoxyls via nucleophile coupling with a 2-alkoxyindoxyl intermediate and showcase its utility in short total syntheses of the alkaloids brevianamide A (7 steps) and trigonoliimine C (6 steps). The developed method is operationally simple and demonstrates broad scope in terms of nucleophile identity and indole substitution, tolerating 2-alkyl substituents and free indole N-H groups, elements beyond the scope of most prior approaches. Spirocyclic indoxyl products are also accessible via intramolecular nucleophilic trapping.

SUBMITTER: Xu F 

PROVIDER: S-EPMC8549782 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature