A simple method for deprotection of the N- and O-carbobenzoxy groups and N-methylation of the desosamine sugar moiety of ketolides. Application to the synthesis of ketolide analogues with various 9-iminoether moieties and their antibacterial activities.
A simple synthetic method for deprotection of the N- and O-carbobenzoxy groups (Cbz) of the desosamine sugar moiety of ketolides is reported. This deprotection method is applicable to the synthesis of a variety of ketolide analogues with various 9-iminoether moieties in good to moderate yield. Among the ketolide derivatives prepared by this method, compound 7g with a quinoline-6-yl moiety showed potent activity against erythromycin-resistant pathogens as well as Haemophilus influenzae.
Iwaki
Tsutomu
T
Discovery Research Laboratories, Shionogi & Co. Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka, Japan.
Nomura
Takashi
T
Narukawa
Yukitoshi
Y
Uotani
Koichi
K
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects; D048628:Ketolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D048628:Ketolides