ABSTRACT
Vancomycin is bactericidal to most Gram-positive organisms, but Gram-negative organisms are resistant. Vancomycin is not absorbed from the gastrointestinal tract, and theantibiotic is used to treat enterocolitis, especially that caused by Clostridium difficile. Vancomycin glycopeptide antibiotics are structurally unique in that amino acids I and 3 are aliphatic amino acids. Synthesis of several N-acyl and N-alkylvancomycins and A82846 antibiotics and their evaluation revealed that the N-alkyl derivatives have a substantial advantage over the parent antibiotics. This chapter examines the in vitro antimicrobial activities of these compounds against penicillin G-susceptible S. aureus XI. All the naturally occurring vancomycin glycopeptide antibiotics that have been reported contain leucine or its methylated analogs. In several naturally occurring vancomycin glycopeptide antibiotics, the phenolic hydroxyl group carries a disaccharide unit. Chemical modification of other functional groups of vancomycin antibiotics far removed from the binding site do not seem greatly to alter the antibacterial activity.
