ENZYMATIC DEACYLATION OF TEICOPLANIN FOLLOWED BY REDUCTIVE ALKYLATION- SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NEW GLYCOPEPTIDES

Novel glycopeptides derived from teicoplanin were prepared and evaluat ed for activity against antibiotic-resistant Gram-positive pathogens. Removal of the fatty acid sidechains of teicoplanin was accomplished b y enzymatic deacylation. The resulting deacylated teicoplanin was subj ected to reductive alkylation resulting in mono- and di-alkylated comp ounds at the 2 possible primary amines. Deacylated teicoplanin was les s active than teicoplanin against enterococci and staphylococci (MIC g reater than or equal to 32 mu g/ml). All mono- and di-alkylated produc ts regained some activity, and some had potent activity against both s taphylococci and glycopeptide-resistant enterococci. MICs of the most potent di-alkylated compounds ranged from 0.25 similar to 2 mu g/ml ag ainst glycopeptide-resistant enterococci.