Synthesis of β-triphosphotriester pronucleotides

[Display omitted] Dinucleoside phosphorochloridite was synthesized from phosphorus trichloride and three nucleoside analogs, 3′-fluoro-2′,3′-dideoxythymidine (FLT), 2′,3′-dideoxy-5-fluoro-3′-thiacytidine (FTC), and 2′,3′-dideoxy-3′-thiacytidine (3TC), in a multistep synthesis. Polymer-bound N-Boc p-acetoxybenzyl 5′-O-2′-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the β-triphosphotriester derivatives containing three different nucleosides.