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

Raffaele Saladino (1) , Veronica Neri (1) , Paola Checconi (2) , Ignacio Celestino (2) , Lucia Nencioni (2) , Anna Teresa Palamara (2, 3) , Marcello Crucianelli (4)

1 Department of Agrobiology and Agrochemistry
2 Department of Public Health and Infectious Diseases
3 San Raffaele Pisana Scientific Institute for Resaearch
4 DSFC - Department of Physical and Chemical Sciences [L'Aquila]

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 H(2)O(2) 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/H(2)O(2) 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.

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Microbiology and Parasitology; Virology

Raffaele Saladino, Veronica Neri, Paola Checconi, Ignacio Celestino, Lucia Nencioni, et al.. Synthesis of 2'-deoxy-1'-homo-N-nucleosides with anti-influenza activity by catalytic methyltrioxorhenium (MTO)/H2O2 oxyfunctionalization.. Chemistry - A European Journal, 2013, 19 (7), pp.2392-404. ⟨10.1002/chem.201201285⟩. ⟨pasteur-01049674⟩