SYNTHESIS OF CASEIN-RELATED PEPTIDES AND PHOSPHOPEPTIDES .4. PHOSPHOROTRIESTER AND PHOSPHITE-TRIESTER PHOSPHORYLATION OF PROTECTED SERINE-CONTAINING PEPTIDES

The phosphorylation of Ac-Ser-NHMe or Ac-Gly-Ser-Gly-NHMe with diphenyl phosphorochlo- ridate/pyridine gave diphenyl hydrogen phosphate in high yield instead of the expected -Ser(PO3Ph2)- peptide. A 31P n.m.r. spectroscopy study of the phosphorylation reaction established that, with the use of diphenyl phosphorochloridate in pyridine, the intermediate diphenyl phosphoro-N-pyridinium chloride was the active phosphorylation species and that phosphorylation of the hydroxy group of Ac-Ser-NHMe or Ac-Gly-Ser-Gly-NHMe was followed by rapid dephosphorylation of the O-(diphenylphosphono)seryl residue. While diethyl phospho- rochloridate/pyridine phosphorylation of Ac-Ser-NHMe also did not give Ac-Ser(PC>3Et2)-NHMe, both the two-step (i) diethyl phosphorochloridite/pyridine, (ii) iodine/water and the two- step (i) diethyl N, N-diethylphosphoramidite/1H-tetrazole, (ii) iodine/water ‘phosphite-triester’ phosphorylation of Ac-Ser-NHMe gave Ac-Ser(PO3Et2)-NHMe in high yield. © 1990 ASEG.