Catalytic Asymmetric Total Synthesis of Roridin E

Abstract

We report the first catalytic asymmetric total synthesis of roridin E, a macrocyclic type D trichothecene. Phase-transfer-catalyzed alkylation of a β-keto ester made in one step from an inexpensive enone delivers the first stereodefined (−)-verrucarol precursor in quantitative yield and >99% ee on a decagram scale, and a Z-selective intramolecular Horner–Wadsworth–Emmons macrocyclization completes the route in 33 steps (longest linear sequence). Synthetic roridin E matched the natural isolate in cytotoxicity across six cancer cell lines.