Stereoselective Synthesis of Elaborate Fragments of Vancoresmycin and Amycomycin Enable Full Stereochemical Assignment

Efficient syntheses of three elaborate fragments of the complex polyketide antibiotics vancoresmycin and amycomycin were accomplished by concise strategies including various boron mediated couplings, an innovative Cu-catalyzed β-boration as well as a highly diastereoselective glycosylation, allowing for a convergent assembly of densely functionalized subunits with excellent diastereoselectivity. Comparative NMR analyses allow full configurational assignment of these potent antimicrobial agents including determination of six previously unknown centers, thus resolving previous contradictory proposals and validating the Kalesse/Kitsche profile hidden Markov model (pHMM) as a reliable tool for predicting hydroxyl- and methyl-bearing stereocenters.