Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.
The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitrile, rather than a carboxamide. Although this modification typically was detrimental to antimicrobial activity, hydrophobic vancomycin aglycon analogues that lack a lipid anchor as well as the disaccharide are detailed that exhibit unusual potency against VanB, but not VanA, resistant bacteria.
McAtee
J Jeffrey
JJ
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550North Torrey Pines Road, La Jolla, CA 92037, USA.
Castle
Steven L
SL
Jin
Qing
Q
Boger
Dale L
DL
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001216:Asparagine / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D014640:Vancomycin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D001216:Asparagine