Synthesis of 2′,3′-Dideoxynucleoside Phosphoesters Using H-Phosphonate Chemistry on Soluble Polymer Support

Céline Crauste (1) , Christian Périgaud (1) , Suzanne Peyrottes (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

Phosphorylation of ddC and 3TC was efficiently performed on soluble poly(ethylene glycol) support. The corresponding 5′-monophosphate derivatives were obtained by oxidation of the support bound 5′-H-phosphonate intermediates. Then, di- and triphosphorylations were carried out using a carbonyldiimidazole activation step followed by nucleophilic substitution with suitable phosphate salts. Trivalent phosphorus chemistry appeared as a good alternative for monophosphate synthesis of acid-sensitive 2′,3′-dideoxynucleosides.

Domaines: Chimie organique; Chimie thérapeutique

Céline Crauste, Christian Périgaud, Suzanne Peyrottes. Synthesis of 2′,3′-Dideoxynucleoside Phosphoesters Using H-Phosphonate Chemistry on Soluble Polymer Support. Journal of Organic Chemistry, 2011, 76 (3), pp.997-1000. ⟨10.1021/jo1022958⟩. ⟨hal-02309881⟩