Synthesis of nonracemic 3-deoxyschweinfurthin B

Abstract

(Chemical Equation Presented) Synthesis of nonracemic 3-deoxyschweinfurthin B has been accomplished through a synthetic sequence including a key cascade cyclization of an epoxy olefin. The intermediate epoxide could be prepared as a single enantiomer through an AD-mix-α (or AD-mix-β) oxidation, and the stereochemistry of the epoxide has been shown to control formation of the two additional stereogenic centers created through the cyclization. Synthetic 3-deoxyschweinfurthin B was found to have potent differential activity in the National Cancer Institute's 60 cell line anticancer assay. This represents the first synthesis of the tetracyclic schweinfurthin skeleton, validating our overall synthetic strategy and providing the first schweinfurthin analogue with activity slightly greater than those of the natural products.