A convenient synthesis of new α-aminoalkylphosphonates, aromatic analogues of arginine as inhibitors of trypsin-like enzymes

A simple and efficient protocol for the synthesis of new N-protected α-aminoalkylphosphonic diphenyl esters––aromatic analogues of arginine––is presented. The crucial, guanylating step was achieved using S-ethyl-N,N′-di(Boc)isothiourea in chloroform and in the presence of Et3N and HgCl2. Deprotection of the derivatives obtained was performed using trifluoroacetic acid in CH2Cl2 or hydrogenolysis over Pd/C. The products are potent inhibitors of trypsin.