Synthesis and Antibacterial Activity of Derivatives of the Glycopeptide Antibiotic A-40926 N-alkylated at the Aminoglucuronyl Moiety

In the last few years, chemical modification of glycopeptide antibiotics has been directed to the derivatives which would be active against highly glycopeptide-resistant (VanA) enterococci while retaining activity against susceptible Gram-positive bacteria including methicillin-resistant and coagulase-negative staphylococci). To date the most promising results have been obtained by the reductive alkylation of antibiotic LY264826 with various lipophilic aldehydes). N-(p-Phenylbenzyl), N-(n-decyl), N-(p-chlorobenzyl) and some other derivatives of LY264826 alkylated at the amino sugar disaccharide branch had demonstrated activity against both glycopeptide-resistant and susceptible Gram-positive bacteria. Here we report the application of the above approach to the derivatization of the glycopeptide antibiotic A-40926 (I).