Synthesis of cruentaren A.

Abstract

Cruentaren A, an antifungal benzolactone produced by the myxobacterium Byssovorax cruenta, is highly cytotoxic against various human cancer cell lines and a highly selective inhibitor of mitochondrial F-ATPase. A convergent and efficient synthesis of cruentaren A is reported, based upon a diastereoselective alkylation, a series of stereoselective aldol reactions utilizing Myers' pseudoephedrine propionamide, an acyl bromide mediated esterification, and a ring-closing metathesis (RCM) as the key steps. The RCM reaction was applied for the first time toward the total synthesis of cruentaren A, which led to a convergent and efficient synthesis of the natural product.