title: Synthesis of 4″-O-desosaminyl clarithromycin derivatives and their anti-bacterial activities.
abstract: A series of new 4″-O-desosaminyl clarithromycin derivatives were designed and synthesized. The efficient synthesis routes of 6-deoxy-desosamine donors 8 and 11 were developed and the methodology of glycosylation of clarithromycin 4″-OH with desosamine was studied. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive pathogens, and compounds 19 and 22 displayed significant improvement of activities against sensitive pathogens and two strains of MRSE, which verified the importance of desosamine in the interaction of macrolide and its receptor, and offered valuable information of the SAR of macrolide 4″-OH derivatives.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Department of Medicinal Chemistry, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Chen
authors.forename: Zhehui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Lei
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017291:Clarithromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006031:Glycosylation; D018942:Macrolides / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017291:Clarithromycin
keywords: Antibacterial activity; Bacterial resistance; Clarithromycin derivatives; Desosamine; Glycosylation; Macrolide antibiotics