One-pot stereoselective synthesis and mechanism of formation of nucleosides-2’,3’-Cyclic Thio/Seleno-Phosphate

A new facile, rapid, stereo- and regio-selective one-pot synthesis of nucleoside-2’,3’-O,O-phosphorothioate/selenoate has been developed. The method is based on the DBU-assisted ring-opening of a new reagent, 2-cyanoethoxy-thio/seleno–dithiophospholane, by uridine producing in a good yield Sp-uridine 2’,3’-O,O-phosphorothioate/selenoate with no need of chiral reagents or chiral separations. This synthetic method was applied also to all four natural nucleosides. We have deciphered the origin of stereo- and regio-selectivity of the reaction by monitoring it with ³¹P NMR. The kinetic product is the Sp isomer, while at elevated temperatures both Sp and Rp isomers are obtained.