Synthesis of diphenyl phosphonate analogues of tyrosine and tryptophan and derived peptides as chymotrypsin inhibitors

The synthesis of alpha-aminophosphonate analogues of tyrosine and tryptophan, e.g. 4 and 5 respectively, and their incorporation into proline-containing dipeptides is reported; of the sequences synthesised, the dipeptide Z-Pro-Trp(P)(OPh)(2) is the only derivative that functions as an irreversible inactivator of the serine proteinase chymotrypsin, in contrast, the tyrosine analogue 4 behaves as a competitive reversible inhibitor of the enzyme and the tryptophan analogue 5 behaves as a slow-binding inhibitor.