Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides

Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):519-36. doi: 10.1080/15257770903053979.

Abstract

9-(2',3'-Dideoxy-2',3'-difluoro-beta-D-arabinofuranosyl)adenine (20), 2-chloro-9-(2',3'-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)adenine (22), as well as their respective alpha-anomers 21 and 23, were synthesized by the nucleobase anion glycosylation of intermediate 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-alpha-D-arabinofuranosyl bromide (13) starting from methyl 5-O-benzyl-3-deoxy-3-fluoro-alpha-D-ribofuranoside (3) and methyl 5-O-benzoyl-alpha-D-xylofuranoside (10). These compounds were evaluated as potential inhibitors of HIV-1 and hepatitis C virus in human PBM and Huh-7 Replicon cells, respectively. The adenosine analog 20 demonstrated potent activity against HIV-1 in primary human lymphocytes with no apparent cytotoxicity. Conformation of pentofuranose ring of nucleoside 20 in solution was studied by PSEUROT calculations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Fluorine Compounds / chemistry*
  • HIV Infections / drug therapy
  • HIV-1 / drug effects*
  • Hepacivirus / drug effects*
  • Hepatitis C / drug therapy
  • Humans
  • Lymphocytes / drug effects
  • Molecular Conformation
  • Purine Nucleosides / chemical synthesis
  • Purine Nucleosides / chemistry*
  • Purine Nucleosides / pharmacology*

Substances

  • Antiviral Agents
  • Fluorine Compounds
  • Purine Nucleosides