Studies Toward the Total Synthesis of Pseudolaric Acid B

Abstract

Pseudolaric acid B is the most potent among the bioactive constituents of tujingpi, a Chinese medicinal herbal preparation used in the treatment of skin fungal infections.1 Besides antifungal activity, it has also been shown to be a microtubule destabilizer, and anti-tumor in vivo. We have been interested in the intramolecular cyclization of metal carbenes with carbonyl groups to generate carbonyl ylides for cycloaddition,2,3 to accomplish the construction of three new bonds in one pot. Using this reaction as the key step, we have achieved the asymmetric synthesis of some natural products, as well as pseudolaric acid A.4,5 Unfortunately, the carbene cyclization cycloaddition step in the proceeded with a low diastereoselectivity of just 1.6:1 for the desired cycloadduct. We have revisited this key step and using alternative chiral rhodium catalysts, we are able to increase the diastereoselectivity of the cycloaddition to 6.0:1. We will report our efforts in a more concise, second-generation synthesis of pseudolaric acid B.