REDUCTIVE ALKYLATION OF GLYCOPEPTIDE ANTIBIOTICS - SYNTHESIS AND ANTIBACTERIAL ACTIVITY

Reductive alkylation of the A82846 family of glycopeptide antibiotics has the potential of producing seven products. N-Alkylation of the dis accharide amino function can be accomplished selectively, and offers t he greatest increase in antibacterial activity. Products resulting fro m N-alkylation of LY264826 (A87846B) provide the most potent derivativ es as compared to other members of this class of antibiotics. Two of t hese derivatives, LY307599 and LY333328 are approximately 500 times mo re active than vancomycin against vancomycin-resistant enterococci.