Biocatalytic Synthesis of Pikromycin, Methymycin, Neomethymycin,Novamethymycin, and Ketomethymycin

摘要

A biocatalytic platform that employs the final two monomodular type I polyketide synthases of the pikromycin pathway in vitro followed by direct appendage of D-desosamine and final C-H oxidation(s) in vivo was developed and applied toward the synthesis of a suite of 12-and 14-membered ring macrolide natural products. This methodology delivered both compound classes in 13 steps (longest linear sequence) from commercially available (R)-Roche ester in ＞10% overall yields.