Fluoro-ketopyranosyl nucleosides: synthesis and biological evaluation of 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives of N4-benzoyl cytosine

Bioorg Med Chem. 2007 Jan 15;15(2):980-7. doi: 10.1016/j.bmc.2006.10.033. Epub 2006 Oct 19.

Abstract

1,2:5,6-Di-O-isopropylidene-alpha-d-glucofuranose on mild oxidation, reduction, fluorination, and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-d-glucopyranose. This was coupled with silylated N(4)-benzoyl cytosine. The nucleoside was deacetylated and after several subsequent protection and deprotection steps afforded the desired 3-fluoro-2-keto-beta-d-glucopyranosyl derivatives. These novel synthesized compounds were evaluated for antiviral and cytotoxic activities against rotavirus, vesicular stomatitis virus, and the human colon adenocarcinoma cell line Caco-2, and have a promising potential in combating the rotaviral infections and in the treatment of colon cancer. As compared to AZT, a nucleoside analogue of reverse transcriptase inhibitor, the novel synthesized 1-(3,4-dideoxy-3-fluoro-beta-d-glycero-hex-3-enopyranosyl-2-ulose)-N(4)-benzoyl cytosine showed to be more effective at lower concentrations in inhibition of rotavirus infection as well as in the same range of antitumor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Caco-2 Cells
  • Cattle
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytosine / analogs & derivatives*
  • Cytosine / chemical synthesis*
  • Cytosine / pharmacology*
  • Drug Screening Assays, Antitumor
  • Haplorhini
  • Humans
  • Indicators and Reagents
  • Monosaccharides / chemical synthesis*
  • Monosaccharides / pharmacology*
  • Oxidation-Reduction
  • Swine
  • Vesicular stomatitis Indiana virus / drug effects
  • Zidovudine / pharmacology

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Indicators and Reagents
  • Monosaccharides
  • Zidovudine
  • Cytosine