Asymmetric formal synthesis of (–)-cryptosporiopsin, a metabolite of Phialophora asterris, and its 3-deschloro congener

Abstract

An asymmetric formal synthesis of the fungal metabolites (–)-cryptosporiopsin and (–)-3-deschloro crypto sporiopsin has been accomplished. The asymmetry was introduced via a diastereoselective [2+2]-cycloaddition between an enoxy-ester, bearing a bulky chiral auxiliary, and dichloroketene. Diastereomeric ratios of 10:1 were obtained from the reaction mixture, but this could be increased by simple crystallization. Completion of the synthesis was only accomplished after the serendipitous discovery of a base-catalyzed rearrangement to furnish the requisite 3-chloroenone moiety.Key words: diastereoselective [2+2]-cycloaddition, rearrangement, chiral auxiliary.