A Concise Synthesis of Pleurotin Enabled by a Nontraditional C-H Epimerization.

ABSTRACT

An 8-step synthesis of a known pentacyclic intermediate toward the natural product pleurotin (1) is described. Pleurotin and related benzoquinone natural products are of great interest for their powerful anticancer and antibiotic activities. The route features a regio- and diastereoselective intermolecular photoenolization/Diels-Alder cycloaddition and an alkoxy-radical-induced hydrogen atom transfer-mediated C-H epimerization to construct pleurotin's carbon framework with appropriate relative stereochemical relationships. The synthesis concludes with a ring-forming benzylic C-H oxidation to deliver oxepane 19.