Chapter 3 - An Adventure in Synthesis Inspired by the Pseudolaric Acids

Abstract

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.