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

Abstract

The synthesis of the title 2′-deoxyadenosine derivatives bearing bipyridine, phenanthroline or terpyridine ligands and their corresponding Ru^II-complexes in position 8 linked viaacetylene 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 Ru^II-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.