Design and synthesis via click chemistry of 8,9-anhydroerythromycin A 6,9-hemiketal analogues with anti-MRSA and -VRE activity.
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.
Sugawara
Akihiro
A
Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan.
Sunazuka
Toshiaki
T
Hirose
Tomoyasu
T
Nagai
Kenichiro
K
Yamaguchi
Yukie
Y
Hanaki
Hideaki
H
Sharpless
K Barry
KB
Omura
Satoshi
S
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*
D000900:Anti-Bacterial Agents; C093673:8,9-anhydroerythromycin A 6,9-hemiketal; D004917:Erythromycin; D003300:Copper