Enzymatic Peroxidation in the Chemoenzymatic Synthesis of 13-Oxoverruculogen

Verruculogens are fumitremorgin alkaloids that contain an eight-membered endoperoxide ring. Due to their unusual structure and bioactivity, there has been much interest in these natural products since their discovery over forty years ago. Similarly, interest in their biosynthesis resulted in the discovery of verruculogen synthase (FtmOx1) that catalyzes endoperoxide formation in these natural products. Herein, we describe our work in this area through the chemoenzymatic synthesis of 13-oxoverruculogen by endoperoxidation of a substrate analog using FtmOx1.