Stereoselective synthesis of phosphoramidate alpha(2-6)sialyltransferase transition-state analogue inhibitors

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3351-4. doi: 10.1016/s0960-894x(03)00672-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Phosphoric Acids / chemical synthesis*
  • Phosphoric Acids / pharmacology
  • Sialyltransferases / chemical synthesis*
  • Sialyltransferases / pharmacology
  • Stereoisomerism

Substances

  • Amides
  • Enzyme Inhibitors
  • Phosphoric Acids
  • phosphoramidic acid
  • Sialyltransferases