Synthesis and enzymatic evaluation of phosphoramidon and its β anomer: Anomerization of α-l-rhamnose triacetate upon phosphitylation

Bioorg Med Chem. 2013 Nov 1;21(21):6778-87. doi: 10.1016/j.bmc.2013.07.052. Epub 2013 Aug 8.

Abstract

A novel and efficient strategy for the synthesis of phosphoramidon and its β anomer has been developed by manipulating the anomerization of α-l-rhamnose triacetate upon phosphitylation. The experimental results suggest that proton transfer, bond rotation, and N atom are the key factors for the anomerization. The determined Ki and Kd values establish that phosphoramidon prepared by this method possesses excellent biological activity, and indicate that the contacts of rhamnose moiety with the enzyme have limited contribution to the binding.

Keywords: Anomerization; Glycopeptide; Phosphoramidate; Phosphoramidite; Phosphoramidon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycopeptides / chemical synthesis*
  • Glycopeptides / chemistry
  • Glycopeptides / metabolism
  • Hydrogen-Ion Concentration
  • Kinetics
  • Protein Binding
  • Protons
  • Rhamnose / chemistry*
  • Stereoisomerism
  • Temperature
  • Thermolysin / antagonists & inhibitors
  • Thermolysin / metabolism

Substances

  • Glycopeptides
  • Protons
  • Thermolysin
  • Rhamnose
  • phosphoramidon