Synthesis of 2'-deoxyadenosine nucleosides bearing bipyridine-type ligands and their Ru-complexes in position 8 through cross-coupling reactions.
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.
Vrábel
Milan
M
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead & IOCB Research Center, Flemingovo nam. 2, CZ-16610 Prague 6, Czech Republic.
Pohl
Radek
R
Klepetárová
Blanka
B
Votruba
Ivan
I
Hocek
Michal
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016174:Hepacivirus / Q000187:drug effects; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003432:Cross-Linking Reagents; D003839:Deoxyadenosines; D008024:Ligands; D011725:Pyridines; D017975:Ruthenium Compounds; C058118:2'-deoxyadenosine