Rapid glycopeptide optimization via neoglycosylation

The present invention generally relates to methods and compositions for generating vancomycin analogs. Specifically the invention relates to generating a vancomycin library through chemoselective ligation of a sugar moiety with a vancomycin aglycon. In particular, the present invention provides a library of vancomycin analogs, where the member of the library comprises at least one vancomycin analog selected from 2′-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 3′-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 4′-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 6′-N-acyldecanoyl-glucosyl vancomycin neoglycoside, 2′-N-acylbiphenyl-glucosyl vancomycin neoglycoside, 3′-N-acylbiphenoyl-glucosyl vancomycin neoglycoside, 4′-N-acylbiphenoyl-glucosyl vancomycin neoglycoside and 6′-N-acylbiphenoyl-glucosyl vancomycin neoglycoside.