Total synthesis of (+)-crocacin A

Abstract

Total synthesis of the potent antifungal and cytotoxic agent (+)-crocacin A is described. The crucial (Z)-5,6-enoic amide moiety in this molecule was built by stereoselective partial reduction of a skipped diyne precursor. The diene, thus obtained, was transformed into a silyl epoxide that was regioselectively opened with an azide ion to furnish an α-azido-β-hydroxyalkylsilane intermediate. Peterson elimination of this β-hydroxysilane component in the final step resulted in the formation of the (Z)-8,9-enamide moiety of the molecule leading to a successful completion of its total synthesis.