title: Design and synthesis via click chemistry of 8,9-anhydroerythromycin A 6,9-hemiketal analogues with anti-MRSA and -VRE activity.
abstract: An erythromycin analogue, 11,12-di-O-iso-butyryl-8,9-anhydroerythromycin A 6,9-hemiketal (1b), was found to be a potential anti-MRSA and anti-VRE agent. The use of copper catalyzed azide-acetylene cycloaddition, and click chemistry, readily provided 10 types of triazole analogues of 1b in good to nearly quantitative yield. Among the library, 5b exhibited activity against MRSA and VRE bacterial strains, representing more than twice the potency of 1b.
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugawara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hanaki
authors.forename: K Barry
authors.initials: KB
authors.lastname: Sharpless
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D016983:Enterococcus / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016106:Methicillin Resistance / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D020713:Vancomycin Resistance / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; C093673:8,9-anhydroerythromycin A 6,9-hemiketal; D004917:Erythromycin; D003300:Copper