Novel azalides derived from sixteen-membered macrolides.
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.
Miura
Tomoaki
T
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Natsume
Satomi
S
Kanemoto
Kenichi
K
Atsumi
Kunio
K
Fushimi
Hideki
H
Sasai
Hiroaki
H
Arai
Takayoshi
T
Yoshida
Takuji
T
Ajito
Keiichi
K
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
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D047028:Macrocyclic Compounds; D018942:Macrolides; D015939:Kitasamycin; C030362:UMP dialdehyde; D017963:Azithromycin; D014542:Uridine Monophosphate