Synthesis of the 5/5-spiroindimicin alkaloids: development of a general synthetic approach and biological investigations.

ABSTRACT: We describe the development of a unified synthetic strategy for the preparation of all known 5/5-spirocyclic spiroindimicin (SPM) alkaloids, namely spiroindimicins B-G. The present synthetic route relies on four fundamental transformations: Grignard-based fragment coupling between halogenated pyrrolemetal and isatin partners, Suzuki coupling to generate a triaryl scaffold encompassing all requisite skeletal atoms of the natural products, Lewis acid-mediated spirocyclization to construct the 5/5-spirocyclic core, and chemoselective lactam reduction. The developed syntheses are step-economic (6-7 steps from commercial materials), scalable, and amenable to analogue synthesis. Preliminary investigations into a catalytic asymmetric spirocyclization towards an enantioselective SPM synthesis are

SUBMITTER: Banerjee A 

PROVIDER: S-EPMC12055039 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature