Iminoalditol-amino acid hybrids: synthesis and evaluation as glycosidase inhibitors

Carbohydr Res. 2007 Sep 3;342(12-13):1850-8. doi: 10.1016/j.carres.2007.03.024. Epub 2007 Mar 28.

Abstract

Cyclization by double reductive amination of D-xylo-hexos-5-ulose with the terminal amino group of alpha-N-Boc-lysine methyl ester gave a 4:1-mixture of (1'R)-N-methoxycarbonyl-(1-N-Boc-amino)pentyl-1-deoxynojirimycin and the corresponding L-ido epimer whereas D-lyxo-hexos-5-ulose furnished the desired N-alkylated 1-deoxymannojirimycin derivative without any observable epimer formation at C-5. By subsequent modification of the lysine moiety, additional chain-extended derivatives as well as fluorescent compounds were obtained. All fluorescent iminoalditol-amino acid hybrids prepared in this study exhibited glycosidase inhibitory activities better than or comparable to the parent compounds'.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucosidases / antagonists & inhibitors
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Imines*
  • Indicators and Reagents
  • Kinetics
  • Mannosidases / antagonists & inhibitors
  • Models, Molecular
  • Sugar Alcohols / chemical synthesis
  • Sugar Alcohols / chemistry*
  • Sugar Alcohols / pharmacology

Substances

  • Amino Acids
  • Enzyme Inhibitors
  • Imines
  • Indicators and Reagents
  • Sugar Alcohols
  • Glucosidases
  • Glycoside Hydrolases
  • Mannosidases