Synthesis of (2S)-O-phosphohomoserine and its C-2 deuteriated and C-3 chirally deuteriated isotopomers: probes for the pyridoxal phosphate-dependent threonine synthase reaction

Abstract

A short efficient synthesis of the threonine synthase substrate (2S)-O-phosphohomoserine and its C-2 deuteriated and C-3 chirally deuteriated isotopomers is described. The synthetic route also provides access to (2S)-homoserine and its C-2 deuteriated and C-3 chirally deuteriated isotopomers in high yield. Preliminary deuterium isotope effect determinations performed using the deuteriated (2S)-O-phosphohomoserines and threonine synthase from E. coli indicate that the removal of protons from both C-2 and C-3 is kinetically important.