Natural product disaccharide engineering through tandem glycosyltransferase catalysis reversibility and neoglycosylation

Org Lett. 2012 Oct 5;14(19):5086-9. doi: 10.1021/ol3023374. Epub 2012 Sep 17.

Abstract

A two-step strategy for disaccharide modulation using vancomycin as a model is reported. The strategy relies upon a glycosyltransferase-catalyzed 'reverse' reaction to enable the facile attachment of an alkoxyamine-bearing sugar to the vancomycin core. Neoglycosylation of the corresponding aglycon led to a novel set of vancomycin 1,6-disaccharide variants. While the in vitro antibacterial properties of corresponding vancomycin 1,6-disaccharide analogs were equipotent to the parent antibiotic, the chemoenzymatic method presented is expected to be broadly applicable.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Biocatalysis*
  • Biological Products / chemistry*
  • Biological Products / metabolism
  • Disaccharides / chemistry*
  • Disaccharides / metabolism
  • Glycosylation
  • Glycosyltransferases / metabolism*
  • Molecular Structure
  • Vancomycin / chemistry*
  • Vancomycin / metabolism

Substances

  • Anti-Bacterial Agents
  • Biological Products
  • Disaccharides
  • Vancomycin
  • Glycosyltransferases