Synthesis of 2'-deoxyadenosine nucleosides bearing bipyridine-type ligands and their Ru-complexes in position 8 through cross-coupling reactions

Org Biomol Chem. 2007 Sep 7;5(17):2849-57. doi: 10.1039/b709245h. Epub 2007 Jul 31.

Abstract

The synthesis of the title 2'-deoxyadenosine derivatives bearing bipyridine, phenanthroline or terpyridine ligands and their corresponding RuII-complexes in position 8 linked via acetylene or phenylene tethers was accomplished through cross-coupling reactions. The Suzuki-Miyaura reactions of boronic acids or the Sonogashira reactions of terminal acetylene derivatives of oligopyridine ligands were performed either on protected 8-bromoadenosines in organic solvents or, more efficiently, directly on unprotected nucleosides in aqueous acetonitrile or DMF. Direct cross-coupling reactions of unprotected nucleosides with RuII-complexes or the oligopyridine-boronic acids or -acetylenes gave the Ru-labelled nucleosides in one step in fair to good yields. This method was also proven to be applicable for direct Ru-labelling of dATP. Terpyridine-containing 2'-deoxyadenosine exerted significant antiviral and cytostatic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / toxicity
  • Cross-Linking Reagents / chemistry*
  • Deoxyadenosines / chemical synthesis*
  • Deoxyadenosines / chemistry
  • Deoxyadenosines / toxicity
  • Hepacivirus / drug effects
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Pyridines / chemistry*
  • Ruthenium Compounds / chemistry*
  • X-Ray Diffraction

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Cross-Linking Reagents
  • Deoxyadenosines
  • Ligands
  • Pyridines
  • Ruthenium Compounds
  • 2'-deoxyadenosine