Stereoselective synthesis of phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors.
The asymmetric synthesis of novel, potent phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors such as (R)-9 (K(i)=68 microM) is described, via condensation of cytidine phosphitamide 6 with key chiral, non-racemic alpha-aminophosphonates, prepared in >98% ee by Mitsunobu azidation followed by Staudinger reduction of the corresponding chiral, non-racemic alpha-hydroxyphosphonates.
Skropeta
Danielle
D
Fachbereich Chemie, Universitaet Konstanz, Fach M 725, D-78457 Konstanz, Germany. d.skropeta@chem.usyd.edu.au
Schwörer
Ralf
R
Schmidt
Richard R
RR
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D012799:Sialyltransferases / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
D000577:Amides; D004791:Enzyme Inhibitors; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D012799:Sialyltransferases