Synthesis and properties of (alpha-P-borano)-nucleoside 5'-triphosphate analogues as potential antiviral agents

Nucleic Acids Symp Ser (Oxf). 2008:(52):81-2. doi: 10.1093/nass/nrn041.

Abstract

The alpha-P-borano modification, where one of the alpha-phosphate oxygens is replaced by borane, of chain terminating nucleoside triphosphates are currently being tested in cell culture and are showing promise as effective viral polymerase inhibitors. The goal of this project is to combine the alpha-P-borano and Nanogel drug delivery technology to increase the antiviral potency of chain terminating sugar and base modified purine nucleosides versus the Hepatitis C Viral RNA dependent RNA polymerase (HCV RdRp). Here we show the synthesis of Cordycepin and 2'-O-methyl alpha-P-borano triphosphate via a one-pot phosphorochloridite synthesis under mild conditions. These analogues will be used for future structure-activity relationship (SAR) studies.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / chemical synthesis
  • Adenosine Triphosphate / chemistry
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / chemistry
  • Hepacivirus / enzymology
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • Thymine Nucleotides / chemical synthesis
  • Thymine Nucleotides / chemistry

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • Boron Compounds
  • Thymine Nucleotides
  • Adenosine Triphosphate
  • RNA-Dependent RNA Polymerase