Total Synthesis of (-)-Indoxamycins A and B

Abstract

The concise total syntheses of (-)-indoxamycins A and B is reported. The chemistry features a seven-step preparation of a highly congested [5.5.6] tricyclic advanced common intermediate from a readily available R-carvone derivative. Key steps involve a Pauson-Khand reaction for the rapid construction of a basic scaffold bearing a quaternary carbon, a copper-catalyzed Michael addition for the introduction of another adjacent all-carbon quaternary stereocenter, and a tandem retro-oxa-Michael addition/1,2-addition/oxa-Michael addition for the installation of a trisubstituted olefin side chain. This synthetic strategy allows for easy access to both enantiomers of this family of natural products and their analogues from cost-effective starting material through straightforward chemical transformations.

Keywords: cycloaddition; indoxamycins; polyketides; tandem reaction; total synthesis.