Efficient Synthesis of Triazole Moiety-Containing Nucleotide Analogs and Their Inhibitory Effects on a Malic Enzyme

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1667-9. doi: 10.1016/j.bmcl.2011.01.107. Epub 2011 Jan 27.

Abstract

Eleven triazole moiety-containing nucleotide analogs were synthesized starting form tetra-O-acetylribose in 55-63% total yields. The synthesis involved two key steps, the lipase-mediated selective deacylation of 1-azido-2,3,5-tri-O-acetyl-β-D-ribofuranoside and the Huisgen 1,3-dipolar cycloaddition between terminal alkynes and the 1-azido ribofuranoside derivative. These analogs showed inhibitory effects against a recombinant Escherichia coli NAD-dependent malic enzyme.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis*
  • Escherichia coli / drug effects
  • Malate Dehydrogenase / antagonists & inhibitors*
  • Nucleotides / chemical synthesis*
  • Triazoles / chemistry*

Substances

  • Enzyme Inhibitors
  • Nucleotides
  • Triazoles
  • Malate Dehydrogenase
  • malate dehydrogenase-(oxaloacetate-decarboxylating) (NAD+)