Toward analogues of MraY natural inhibitors: synthesis of 5'-triazole-substituted-aminoribosyl uridines through a Cu-catalyzed azide-alkyne cycloaddition

J Org Chem. 2013 Oct 18;78(20):10088-105. doi: 10.1021/jo4014035. Epub 2013 Oct 7.

Abstract

A straightforward strategy for the synthesis of triazole-containing MraY inhibitors has been developed. It involves the sequential introduction of a terminal alkyne at the 5' position of an uridine derivative and O-glycosylation with a protected aminoribose leading to an elaborated alkyne scaffold. An efficient Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allowed the introduction of chemical diversity toward a small library of inhibitors.

MeSH terms

  • Alkynes / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Azides / chemistry
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry*
  • Catalysis
  • Copper / chemistry*
  • Cycloaddition Reaction
  • Drug Resistance, Bacterial
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Glycosylation
  • Transferases (Other Substituted Phosphate Groups)
  • Transferases / antagonists & inhibitors*
  • Transferases / chemistry*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Uridine / chemical synthesis*
  • Uridine / chemistry

Substances

  • Alkynes
  • Anti-Bacterial Agents
  • Azides
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Triazoles
  • Copper
  • Transferases
  • Transferases (Other Substituted Phosphate Groups)
  • mraY protein, Bacteria
  • Uridine