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

• Published in: Organic & biomolecular chemistry 2007-01, Vol.5 (17), p.2849
• Main Authors: Vrábel, Milan, Pohl, Radek, Klepetárová, Blanka, Votruba, Ivan, Hocek, Michal
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b709245h

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.