C-(2-Deoxy-d-arabino-hex-1-enopyranosyl)-oxadiazoles: synthesis of possible isomers and their evaluation as glycogen phosphorylase inhibitors

Carbohydr Res. 2015 Aug 14:412:71-9. doi: 10.1016/j.carres.2015.04.016. Epub 2015 May 2.

Abstract

Synthetic methods were elaborated for d-glucals attached to oxadiazoles by a C-C bond. Introduction of the double bond was effected by either DBU induced elimination of PhCOOH from the O-perbenzoylated glucopyranosyl precursors or Zn/N-methylimidazole mediated reductive elimination from the 1-bromoglucopyranosyl starting compounds. Alternatively, heterocyclizations of 2-deoxy-d-arabino-hex-1-enopyranosyl cyanide were also carried out. Test compounds were obtained by Zemplén debenzoylation, however, none of them showed significant inhibition of rabbit muscle glycogen phosphorylase b.

Keywords: C-Glycosyl compounds; Glycogen phosphorylase; Inhibitor; Oxadiazoles; d-Glucal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Glycogen Phosphorylase / metabolism
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Imidazoles / chemistry
  • Isomerism
  • Muscles / metabolism
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Rabbits

Substances

  • Enzyme Inhibitors
  • Glycosides
  • Imidazoles
  • Oxadiazoles
  • Glycogen Phosphorylase
  • 1-methylimidazole