Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity.
Cooper RD,
Snyder NJ,
Zweifel MJ,
Staszak MA,
Wilkie SC,
Nicas TI,
Mullen DL,
Butler TF,
Rodriguez MJ,
Huff BE,
Thompson RC.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Reductive alkylation of the A82846 family of glycopeptide antibiotics has the potential of producing seven products. N-Alkylation of the disaccharide amino function can be accomplished selectively, and offers the greatest increase in antibacterial activity. Products resulting from N-alkylation of LY264826 (A82846B) provide the most potent derivatives as compared to other members of this class of antibiotics. Two of these derivatives, LY307599 and LY333328 are approximately 500 times more active than vancomycin against vancomycin-resistant enterococci.
PMID: 8698642 [PubMed - indexed for MEDLINE]