Stereoselective synthesis of 2'-amino-2',3'-dideoxynucleosides by nitrone 1,3-dipolar cycloaddition: a new efficient entry towards D4T and its 2-methyl analogue

An efficient access to 2'-(dimethylamino)-2',3'-dideoxynucleosides is reported. The synthetic strategy relies on the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to allyl acetate, followed by reductive ring opening to substituted lactones, DIBALH reduction to the corresponding 3-(dimethylamino) tetrahydro-2-furanols, and coupling with silylated thymine. The removal of the dimethylamino group by Cope elimination affords a new formal synthesis of d4T and analogous unsaturated 2',3'-dideoxynucleosides.