NOVEL GLYCOPEPTIDE ANTIBIOTICS - N-ALKYLATED DERIVATIVES ACTIVE AGAINST VANCOMYCIN-RESISTANT ENTEROCOCCI

LY26426 (A82846B) is a naturally-occurring glycopeptide antibiotic, di ffering from vancomycin in the stereochemistry of the amino-sugar of t he disaccharide function, and the presence of a third sugar attached a t the benzylic position of amino acid residue 6. Despite these seeming ly differences, LY264826 is approximately 10 times more active than va ncomycin against the enterococci. In the pursuit of new antibiotics ac tive against multiresistant Gram-positive organisms, an extensive side chain SAR was developed focusing on the reductive alkylation of LY264 826 at the amino function of the disaccharide moiety. A new series of derivatives having varying degrees of structural diversity in the side chain (e.g. varying lengths and degrees of rigidity) was found to hav e potent activity staphylococci and streptococci as good or better tha n vancomycin.