Naslov
Synthesis and Properties of Macrolones Characterized by Two Ether Bonds in the Linker

Autori
Palej Jakopović, Ivana ; Kragol, Goran ; Forrest, Andrew K. ; Frydrych, Catherine S.V. ; Štimac, Vlado ; Kapić, Samra ; Matanović-Škugor, Maja ; Čipčić Paljetak, Hana ; Jelić, Dubravko ; Holmes, David J. ; Hickey, Deirdre M. B. ; Verbanac, Donatella ; Eraković Haber, Vesna ; Alihodžić, Sulejman

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 18 (2010), 17; 6578-6588

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
macrolide; quinolone; 4”-ether bond; antibacterial activity

Sažetak
In this paper synthesis of macrolones 1-18 starting from azithromycin is reported. Two key steps in the construction of the linker between macrolide and quinolone moiety, are formation of central ether-bond by alkylation of unactivated OH group, and formation of terminal C-C bond at 6- position of the quinolone unit. Due to the difficulty in formation of these two bonds the study of alternative synthetic methodologies and optimization of the conditions for the selected routes was required. Formation of C-4’’O-ether bond was completed by modified Michael addition, whereas O-alkylation via diazonium cation proved to be the most effective in formation of the central allylic or propargylic ether bond. Comparison of Heck and Sonogashira reaction revealed the former as preferred route to the C-C bond formation at C(6) position of the quinolone unit. Most of the target compounds exhibited highly favorable antibacterial activity against common respiratory pathogens, without significant cytotoxicity profile when tested in vitro on eukaryotic cell lines.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Farmacija

POVEZANOST RADA