CARBOXAMIDES AND HYDRAZIDE OF GLYCOPEPTIDE ANTIBIOTIC EREMOMYCIN SYNTHESIS AND ANTIBACTERIAL ACTIVITY

Carboxamides and hydrazide of glycopeptide antibiotic eremomycin were obtained by a direct reaction of the carboxy group of eremomycin with an appropriate amine or hydrazine using diphenyl phosphorazidate as a condencing agent. Eremomycin hydrazide was also obtained by hydrazinol ysis of the eremomycin methyl ester. Use of dicyclohexylcarbodiimide o r 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide for amidation led to t he corresponding eremomycin ureides. The ESI-MS data indicate that ere momycin and its amides exist as dimers. The carboxamide, methylamide a nd benzylamide of eremomycin were as active against Gram-positive bact eria as the parent antibiotic, and the methylamide, benzylamide and hy drazide were almost an order of magnitude more active than eremomycin against Staphylococcus epidermidis clinical isolates in vitro. Amide o f eremomycin as well as ureides were devoid of histamine liberating pr operties, which demonstrates that protection of the carboxyl group lea ds to a decrease in the allergenic properties.