Synthesis of unnatural 3′-phospha-2′-deoxyfuranose nucleoside analogues.

Bénédicte Dayde (1) , Claire Pierra (2) , Gilles Gosselin (3) , Dominique Surleraux (2) , Amadou Tidjani Ilagouma (4) , Jean-Noël Volle (1) , David Virieux (1) , Jean-Luc Pirat (1)

1 ICGM ICMMM - Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier
2 Idenix Pharmaceuticals
3 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
4 Departement de Chimie

This Letter describes the synthesis of racemic analogues of unnatural 2′-deoxy nucleoside with a phosphorus atom replacing the carbon atom in the 3′-position. A seven-step sequence was developed in racemic series to afford unnatural 3′-phospha-2′-deoxyfuranose nucleosides. The phospha nucleoside analogues were tested against HCV, but did not show any antiviral activity at a 10 μM maximum concentration used for the inhibition assays of analogues 2-T, 2-C and 4-Tα.

Mots clés: Deoxy nucleosides analogues; Pudovik reaction; P-alkylation reaction; Radical deiodination

Domaines: Chimie organique

Bénédicte Dayde, Claire Pierra, Gilles Gosselin, Dominique Surleraux, Amadou Tidjani Ilagouma, et al.. Synthesis of unnatural 3′-phospha-2′-deoxyfuranose nucleoside analogues.. Tetrahedron Letters, 2014, 55 (46), pp.6328-6330. ⟨10.1016/j.tetlet.2014.09.102⟩. ⟨hal-01084091⟩