title: Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Cooper
authors.forename: N J
authors.initials: NJ
authors.lastname: Snyder
authors.forename: M J
authors.initials: MJ
authors.lastname: Zweifel
authors.forename: M A
authors.initials: MA
authors.lastname: Staszak
authors.forename: S C
authors.initials: SC
authors.lastname: Wilkie
authors.forename: T I
authors.initials: TI
authors.lastname: Nicas
authors.forename: D L
authors.initials: DL
authors.lastname: Mullen
authors.forename: T F
authors.initials: TF
authors.lastname: Butler
authors.forename: M J
authors.initials: MJ
authors.lastname: Rodriguez
authors.forename: B E
authors.initials: BE
authors.lastname: Huff
authors.forename: R C
authors.initials: RC
authors.lastname: Thompson
mesh_terms: D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; C100707:LY 307599; D000077427:Lipoglycopeptides; C057893:chloroorienticin A; D014640:Vancomycin; C100708:oritavancin