Modular Synthesis of Candidate Indole-based Insulin Mimics by Claisen Rearrangement

A modular synthetic route to (indolyl)kojic acid anti-diabetes agents has been developed. Sonogashira coupling of a protected iodoaniline with a propargyl kojate was used to construct an (indole)methyl kojate. Its heteroaromatic Claisen rearrangement, followed by tautomerization to return the indole and pyrone rings, was used to create the biaryl C-C bond. This route should enable collections of insulin mimic drug candidates to be prepared from a few basic building blocks.