Synthesis of peptidomimetics: An evaluation of p-nitrophenyl carbamate of ethylenediamine

The application of p-nitrophenyl carbamate of Boc-ethylenediamine for the solid-phase synthesis of peptidomimetics was examined. The per step yield of coupling was estimated using mass spectrometry, based on the repeated coupling of the same monomer in the synthesis of alkylurea oligomers. Introduction of the urea moiety at the terminus of the chain adjacent to the resin was accomplished by the use of the BHA resin in the assembly of the chain and liquid HF in the cleavage step. In addition, an alkylurea oligomer was treated with bis(p-nitrophenyl) carbonate followed by ammonolysis in order to obtain a urea moiety at the terminus distant from the resin. Aside from the expected oligomer, a product was obtained in which the terminal alkylurea had undergone cyclization. Finally, four peptidomimetics, analogues of 1-4 enkephalin fragment, containing up to four alkylurea units instead of glycine residues, were synthesized. Two of these peptidomimetics were examined for opioid activity and turned out to be active in the guinea pig ileum assay.