Synthesis of Cryptophycin 52 Using the Sharpless Asymmetric Dihydroxylation: Diol to Epoxide Transformation Optimized for a Base-Sensitive Substrate

A synthesis of cryptophycin 52 (2) is reported using a Sharpless asymmetric dihydroxylation (AD) strategy to install the epoxide moiety. The high stereoselectivity of the AD reaction that allows for an efficient means of preparing the epoxide is in contrast to the standard direct epoxidation of cryptophycin substrates, which proceeds with poor diastereoselectivity. Methodology for conversion of the diol AD product to the requisite epoxide is disclosed. The transformation has been optimized to proceed in high yield in the presence of base sensitive functionality.