Synthesis of 2'-deoxy-1'-homo-N-nucleosides with anti-influenza activity by catalytic MTO/H2O2 oxyfunctionalization

This paper describes a new route for the synthesis of 1'-homo-N-nucleoside derivatives by means of either MTO or MTO supported catalysts, with H2O2 as primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring, as well as, the N-heteroatom oxidation, were operative processes, regardless of the type of used substrate, i.e. purine or pyrimidine derivatives. In addition, the oxidation of 1'-homo-N-thionucleosides, evidenced the occurrence of site-specific oxidative nucleophilic substitutions of the heterocyclic ring. MTO/H2O2 system showed, in general, high reactivity under both homogeneous and heterogeneous conditions, affording the final products with high conversion values of substrates and from medium to high yields. Many of the novel 1'-homo-N-nucleosides analogues were active against influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms.