Synthesis of nucleosides, nucleotides and nucleic acids bearing bipyridine-type ligands

An efficient methodology of construction of base-modified nucleosides bearing oligopyridine ligands, based on the Sonogashira or Suzuki cross-coupling reaction of halogenated nucleosides, was developed. This methodology was then successfully employed in construction of base-modified DNA bearing oligopyridine ligands which were studied in post-synthetic complexation with labile transition metals. The first step in construction of modified DNA is the synthesis of deoxynucleoside triphosphate (dNTPs) bearing various metal chelating groups, which are in second step enzymatically incorporated into DNA by primer extension experiment. The first task was the synthesis of dNTPs bearing different oligopyridine ligands, which could be done by aqueous phase cross-coupling reaction with suitable building blocks or by triphosphorylation of oligopyridine-modified deoxynucleosides. Both ways were successfully used. Aqueous phase Sonogashira cross-coupling was used for synthesis of dNTPs bearing oligopyridine ligands attached via short and rigid acetylene tether, while classical triphosphorylation of modified nucleosides was used for construction of dNTPs bearing oligopyridine ligands attached via long and flexible octadiyne linker. Sonogashira cross-coupling reaction was also used for preparation of both types of..