Synthesis and mode of action of hydrophobic derivatives of the glycopeptide antibiotic eremomycin and des-(N-methyl-D-leucyl)eremomycin against glycopeptide-sensitive and -resistant bacteria.

Des-(N-methyl-D-leucyl)eremomycin was obtained by Edman degradation of eremomycin. Derivatives with a hydrophobic substituent at the exterior of the molecule were then synthesized, and their antibacterial activities were compared with similar derivatives of eremomycin. Comparison of derivatives of eremomycin containing the n-decyl or p-(p-chlorophenyl)benzyl substituent in the eremosamine moiety (N') and n-decyl or p-(p-chlorophenyl)benzylamides with similar derivatives of eremomycin possessing the damaged peptide core (a defective binding pocket) showed that compounds of both types are almost equally active against glycopeptide-resistant strains of enterococci (GRE), whereas eremomycin derivatives are more active against staphylococci.

Antibacterial activity of synthetic analogues based on the disaccharide structure of moenomycin, an inhibitor of bacterial transglycosylase.

Moenomycin is a natural product glycolipid that inhibits the growth of a broad spectrum of Gram-positive bacteria. In Escherichia coli, moenomycin inhibits peptidoglycan synthesis at the transglycosylation stage, causes accumulation of cell-wall intermediates, and leads to lysis and cell death. However, unlike Esc.