Synthesis and antibacterial activity of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin

Two series of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 4j and 4k were the most potent activity against erythromycin-susceptible Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, which were comparable to those of clarithromycin and azithromycin. Compounds 4d, 4h and 4i showed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and compounds 4h and 4i displayed greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. Compound 7c exhibited improved activity against erythromycin-resistant S. pneumoniae encoded by the erm and mef genes.

Graphical abstractNovel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin were synthesized and evaluated. Some derivatives showed excellent activity against erythromycin-susceptible bacteria and greatly improved activity against erythromycin-resistant Streptococcus pneumoniae.Figure optionsDownload full-size imageDownload as PowerPoint slide