Inhibition of the enzyme ribonucleotide reductase is an appealing concept for the rational drug design against rapid proliferation of systems such as viruses and cancer cells. Synthesis of 2'-thionucleoside analogs as possible inhibitors of the enzyme was targeted in this research. For protecting the reactive thiol group, mixed disulfides were prepared as precursors of the sulfur-containing nucleosides. The thionucleoside obtained are currently under biological studies.
Fluorinated compounds are widely used in biochemistry, medicinal chemistry, and pharmacology. Synthesis of 2'-deoxy-2'-fluoroadenosine and its arabino epimer as well as 3’-deoxy-3'-fluoroadenosine and its xylo epimer were also targeted in order to study the electronic versus steric β-fluorine effects in radical deoxygenation of fluorine containing pentofuranose nucleosides. Our results clearly show that steric effect of the heterocyclic base from the β-face of the sugar is decisive, favoring the incorporation of deuterium from the less hindered α-face.
