Synthesis of hydropobic N′-mono and N′,N″-double alkylated eremomycins inhibiting the transglycosylation stage of bacterial cell wall biosynthesis

Article abstract of DOI:10.7164/antibiotics.54.455

A series of hydrophobic N′-mono and N′,N″-double alkylated derivatives of the glycopeptide antibiotic eremomycin were synthesized by reductive alkylation after preliminary protection of the N-terminal amino group of the peptide backbone. The investigation of the antibacterial activity in vitro showed that N′-C₁₀H₂₁- and N′-p-(p-chlorophenyl)benzyl derivatives of eremomycin are the most active against vancomycin-resistant enterococci among the compounds obtained though they are less effective than the corresponding lipophilic derivatives of vancomycin. The introduction of two hydrophobic substituents led to a decrease in activity against both susceptible and resistant bacteria. The biochemical evaluation of the mode of action revealed that in addition to binding to D-Ala-D-Ala these compounds also have an alternative mechanism of action that does not require substrate binding.