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Original scientific paper

3-O-Acyl Derivatives of Bridged-15-Membered Azalides: Synthesis, Structural Determination and Antibacterial Activity

Andrea Fajdetić
Gabrijela Kobrehel
Gorjana Lazarevski
Vlado Štimac
Stjepan Mutak


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Abstract

The synthesis, structural determination and biological evaluation of 15-membered azalides acylated at the C-3 position are described. 3-Descladinosyl-9a,l1-cyclic carbamate of the 9a-aza- 9a-homoerythromycin A and their 12-O-alkyl derivatives were synthesized via acidic hydrolysis of adequate 3-cladinosyl analogues. Protections of 2'-hydroxyl group were performed to furnish starting compounds for acylation of the C-3-hydroxyl group. After deprotection various 3-O-acyl derivatives were obtained and their structures confirmed by spectroscopic methods (IR, MS, NMR). The new compounds were evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria and their activities compared with those of parent derivatives. The 3-O-acyl derivatives exhibited improved antibacterial activity, but it was lower than by standard macrolides.

Keywords

azalides; synthesis; acylation; NMR spectroscopy

Hrčak ID:

26

URI

https://hrcak.srce.hr/26

Publication date:

15.6.2005.

Article data in other languages: croatian

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