Synthesis of fused bicyclic thioglycosides of N-acylated glucosamine as analogues of mycothiol

Carbohydr Res. 2007 Sep 3;342(12-13):1943-6. doi: 10.1016/j.carres.2007.04.019. Epub 2007 Apr 29.

Abstract

The synthesis of a fused bicyclic thioglycoside analogue of mycothiol, (3R)-3-acetylamino-4-one-6,7-dihydro-(1',2'-dideoxy-beta-D-glucopyranoso)[2',1'-f]-1,5-thiazepane (5), is reported. Treatment of phthalimido-protected peracetylated glucosamine with N-acetyl-cysteine and boron trifluoride-etherate gave the beta-linked thioglycoside, which was deprotected and cyclized, using HOBt and EDCl to form the lactam and giving the target structure. This mycothiol mimic and its tri-O-acetate will be investigated as potential inhibitors of enzymes involved in the biosynthesis of mycothiol. The protected derivative also has the potential to be an alpha-selective N-cysteinyl glucosamine donor; however, initial glycosylation attempts failed due to the apparent stability of the fused bicyclic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Carbohydrate Conformation
  • Cysteine / chemistry*
  • Glucosamine / chemistry*
  • Glycopeptides / chemistry*
  • Inositol / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Thioglycosides / chemical synthesis*
  • Thioglycosides / chemistry

Substances

  • Bridged Bicyclo Compounds
  • Glycopeptides
  • Thioglycosides
  • mycothiol
  • Inositol
  • Cysteine
  • Glucosamine
  • Acetylglucosamine