Synthesis of 2′-deoxy-1′-homo-N-nucleosides with anti-influenza activity by catalytic methyltrioxorhenium (MTO)/H2O2 oxyfunctionalization

This paper describes a new route for the synthesis of 1′-homo-N- nucleoside derivatives by means of either methyltrioxorhenium (MTO) or supported MTO catalysts, with H2O2 as the primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring and the N heteroatom oxidation were operative processes, regardless of the type of substrate used, that is, purine or pyrimidine derivatives. In addition, the oxidation of 1′-homo-N-thionucleosides, showed the occurrence of site-specific oxidative nucleophilic substitutions of the heterocyclic ring. The 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-nucleoside analogues were active against the influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms. Antiviral activity: Under either homogeneous or heterogeneous catalytic conditions, the high reactivity of the methyltrioxorhenium (MTO)/H2O2 oxidative system allowed the synthesis of new 1′-homo-N-nucleoside derivatives through a selective oxyfunctionalization of the heterocyclic ring and of the N-heteroatom moiety (see scheme). Many of the modified nucleosides have been shown to be active against the influenza A virus. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.