Novel Azalides Derived from Sixteen-Membered Macrolides

• Published in: Journal of antibiotics Vol. 60; no. 7; pp. 407 - 435
• Main Authors: Miura, Tomoaki, Natsume, Satomi, Kanemoto, Kenichi, Atsumi, Kunio, Fushimi, Hideki, Sasai, Hiroaki, Arai, Takayoshi, Yoshida, Takuji, Ajito, Keiichi
• Format: Journal Article
• Language: English
• Published: Japan Nature Publishing Group 01-07-2007
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Aza Compounds - chemical synthesis; Aza Compounds - pharmacology; Azithromycin - analogs & derivatives; Azithromycin - chemistry; Azithromycin - pharmacology; Bacteria - drug effects; Green chemistry; Humans; Kitasamycin - chemical synthesis; Kitasamycin - pharmacology; Macrocyclic Compounds; Macrolides - chemical synthesis; Macrolides - chemistry; Macrolides - pharmacology; Microbial Sensitivity Tests; Osmium; Uridine Monophosphate - analogs & derivatives; Uridine Monophosphate - chemical synthesis; Uridine Monophosphate - pharmacology
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2007.55

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.