An adventure in synthesis inspired by the pseudolaric acids

Abstract

This account describes efforts that culminated in the first total synthesis of pseudolaric acid A, an antitumor and antiangiogenic natural product. A first retrosynthesis based on a reductive aldol reaction failed to generate the desired carboskeleton with the correct relative stereochemistry, although the copper hydride-induced reductive aldol cyclization developed for this key step turned out to be a useful synthetic methodology on its own. A second retrosynthesis based on the carbene cyclization cycloaddition cascade reaction as the key step was ultimately successful in constructing pseudolaric acid A, as well as other natural products.