Enzymatic deacylation of teicoplanin followed by reductive alkylation: Synthesis and antibacterial activity of new glycopeptides

Novel glycopeptides derived from teicoplanin were prepared and evaluated for activity against antibiotic-resistant Gram-positive pathogens. Removal of the fatty acid sidechains of teicoplanin was accomplished by enzymatic deacylation. The resulting deacylated teicoplanin was subjected to reductive alkylation resulting in mono- and di-alkylated compounds at the 2 possible primary amines. Deacylated teicoplanin was less active than teicoplanin against enterococci and staphylococci (MIC greater than or equal to 32 mu g/ml). All mono- and di-alkylated products regained some activity, and some had potent activity against both staphylococci and glycopeptide-resistant enterococci. MICs of the most potent di-alkylated compounds ranged from 0.25 similar to 2 mu g/ml against glycopeptide-resistant enterococci.