Asymmetric synthesis of the left hand portion of the azinomycins
A nine step synthesis of the left hand portion of the azinomycins is described starting from 3,3-dimethylacrylic acid. The approach relies on a Sharpless asymmetric dihydroxylation (AD) reaction to install the requisite (2S,3S)-stereochemistry of epoxy alcohol 4. This epoxide is converted to crystalline amide derivative 12 whose structure and absolute stereochemistry have been unambiguously established using X-ray crystallography. Coupling of epoxy alcohol (2S,3S)-4 with naphthoyl chloride 16 and subsequent manipulations furnish epoxy amide (2S,3S)-1 identical in all respects with the natural material.