Modular Synthesis of the Potent Antibiotic Amycolamicin and Diastereomeric Analogues Thereof

A modular approach to the potent, broad-spectrum antibiotic amycolamicin and seven diastereomeric analogues is described. The synthesis features bioinspired construction of the high-carbon amycolose segment, gold(I)-catalyzed high-yielding O-glycosylation of the trans-decalin scaffold, N-glycosylation of the bromoacetylated l-valine derivative, and condition-tuned late-stage C-acylation of the tetramic acid motif. An assessment of the antibacterial properties of these synthetic molecules indicated that the correct stereochemistry is essential for the potent bioactivity of amycolamicin.