Synthesis and α-Glucosidase II inhibitory activity of valienamine pseudodisaccharides relevant to N-glycan biosynthesis

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5219-23. doi: 10.1016/j.bmcl.2011.07.046. Epub 2011 Jul 21.

Abstract

Valienol-derived allylic C-1 bromides have been used as carbaglycosyl donors for α-xylo configured valienamine pseudodisaccharide synthesis. We synthesised valienamine analogues of the Glc(α1→3)Glc and Glc(α1→3)Man disaccharides representing the linkages cleaved by α-Glucosidase II in N-glycan biosynthesis. These (N1→3)-linked pseudodisaccharides were found to have some α-Glucosidase II inhibitory activity, while two other (N1→6)-linked valienamine pseudodisaccharides failed to inhibit the enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Chemistry Techniques, Synthetic
  • Cyclohexenes / chemical synthesis
  • Cyclohexenes / chemistry
  • Cyclohexenes / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolase Inhibitors*
  • Hexosamines / chemical synthesis
  • Hexosamines / chemistry
  • Hexosamines / pharmacology*
  • Molecular Conformation
  • Polysaccharides / biosynthesis*
  • Polysaccharides / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism

Substances

  • Cyclohexenes
  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Hexosamines
  • Polysaccharides
  • valienamine
  • alpha-Glucosidases