Synthesis and Antibacterial Activity of Novel 4″‐O‐Carbamoyl Erythromycin‐A Derivatives

Novel 4″‐O‐carbamoyl erythromycin‐A derivatives were designed, synthesized, and evaluated for their in‐vitro antibacterial activities. All of the 4″‐O‐carbamoyl derivatives showed excellent activity against erythromycin‐susceptible Staphylococcus aureus ATCC25923, Streptococcus pyogenes, and Streptococcus pneumoniae ATCC49619. Most of the 4″‐O‐arylalkylcarbamoyl derivatives displayed potent activity against erythromycin‐resistant S. pneumoniae encoded by the mef gene and greatly improved activity against erythromycin‐resistant S. pneumoniae encoded by the erm gene or the erm and mef genes. In particular, the 4″‐O‐arylalkyl derivatives 4c–4e and 4g were found to possess the most potent activity against all the tested erythromycin‐susceptible strains, which were comparable to those of erythromycin, clarithromycin, or azithromycin. 4″‐O‐Arylalkyl derivatives 4e and 4g were the most effective against erythromycin‐resistant S. pneumoniae encoded by the mef gene (0.25 and 0.25 µg/mL). 4″‐O‐Arylalkyl derivatives 4a and 4b exhibited significantly improved activity against erythromycin‐resistant S. pneumoniae encoded by the erm gene. In contrast, the 4″‐O‐alkylcarbamoyl derivatives hardly showed improved activity against all the tested erythromycin‐resistant strains.