Stereoselective synthesis of phosphoramidate α(2-6)Sialyltransferase transition-State analogue inhibitors

The asymmetric synthesis of novel, potent phosphoramidate α(2-6)sialyltransferase transition-state analogue inhibitors such as ( R)- 9 ( K i=68 μM) is described, via condensation of cytidine phosphitamide 6 with key chiral, non-racemic α-aminophosphonates, prepared in >98% ee by Mitsunobu azidation followed by Staudinger reduction of the corresponding chiral, non-racemic α-hydroxyphosphonates. The asymmetric synthesis of novel, potent phosphoramidate α(2-6)sialyltransferase transition-state analogue inhibitors such as ( R)- 9 ( K i=68 μM) is reported.