title: Novel azalides derived from sixteen-membered macrolides.
abstract: The design and synthesis of novel 15-membered 11-azalides and 16-membered 11,12-diazalide starting from 16-membered macrolides are reported. A mobile linear dialdehyde was isolated via a cyclic tetraol which was prepared by osmium oxidation of a conjugated diene. One-pot macrocyclization of this dialdehyde with an amine or a diamine afforded corresponding 15-membered azalides or 11,12-diazalide. Fundamental SAR studies of 15-membered 11-azalides disclosed their potentiality as a lead molecule for further chemical modifications. For environmental preservation, sustainable chemistry for synthesis of these azalides is also discussed.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Miura
authors.forename: Satomi
authors.initials: S
authors.lastname: Natsume
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kanemoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Atsumi
authors.forename: Hideki
authors.initials: H
authors.lastname: Fushimi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasai
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Arai
authors.forename: Takuji
authors.initials: T
authors.lastname: Yoshida
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ajito
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D017963:Azithromycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D006801:Humans; D015939:Kitasamycin / Q000138:chemical synthesis / Q000494:pharmacology; D047028:Macrocyclic Compounds; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D047028:Macrocyclic Compounds; D018942:Macrolides; D015939:Kitasamycin; C030362:UMP dialdehyde; D017963:Azithromycin; D014542:Uridine Monophosphate