A Biosynthetic Proposal for Ring Formation in the Antitumor Agent Halichomycin. Asymmetric Synthesis of the AB-Carbon Backbone of Halichomycin

A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative
prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the α-keto N-acylimine 3 followed by tandem
nucleophilic addition of the C(16)-hydroxyl to form the hemimacrolactam. A stereospecific Michael ring closure and enol protonation complete
C-ring assembly. So far, synthetic efforts toward 1 have resulted in 8.