Synthesis of 2-fluoronoraristeromycin and its inhibitory activity against Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3963-5. doi: 10.1016/j.bmcl.2003.08.074.

Abstract

Palladium-coupling reaction of (1S, 4R)-cis-4-acetoxy-2-cyclopenten-1-ol with sodium salt of 2-fluoroadenine resulted in the formation of (1S,4R)-4-(6-amino-2-fluoro-9H-purin-9-yl)cyclopent-2-en-1-ol. Subsequent oxidation was carried out with osmium tetraoxide (OsO(4)) in the presence of 4-methylmorpholine N-oxide (NMO) to give 2-fluoronoraristeromycin, possessing significant inhibitory activity against recombinant Plasmodium falciparum SAH hydrolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / chemical synthesis*
  • Adenosine / toxicity*
  • Adenosylhomocysteinase / antagonists & inhibitors*
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Molecular Conformation
  • Molecular Structure
  • Plasmodium falciparum / enzymology*

Substances

  • 2-fluoronoraristeromycin
  • Antimalarials
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Adenosylhomocysteinase
  • Adenosine