Enantioselective Total Synthesis of (-)-Psiguadial A

Abstract

The first enantioselective total synthesis of the antiproliferative natural product (-)-psiguadial A is reported. This approach features the enantioselective synthesis of a complex tricyclic terpenoid precursor, the union of that precursor with a polyketide component by an enolate-ortho-quinone methide coupling reaction to form a highly congested carbon─carbon bond, and an acid-mediated intramolecular hydration ring-closure leveraging a fully substituted alkene to generate the unique oxepane core structure of the natural product.

Keywords: Meroterpenoids; Natural products synthesis; Stereoselective synthesis; Umpolung; ortho‐Quinone methides.