A novel green synthesis of α/β-amino acid functionalized pyrimidinone peptidomimetics using triazole ligation through click-multi-component reactions

An innovative synthetic pathway for the preparation of a new series of triazole-decorated dihydropyrimidinone peptidomimetics with skeletal α or β-amino acid residue is reported. The protocol involves two synthetic steps with an initial solvent-free and catalyst-free synthesis of propargylated dihydropyrimidinone precursors using Biginelli condensations. The subsequent cycloaddition reactions of pyrimidinone alkynes with small peptide like azides prepared from Ugi or alternate Mannich type multi-component reactions afforded the triazole decorated pyrimidinone peptide conjugates in excellent yield with high regio and stereospecificities. In total, a scaffold diversity contains 11 new pyrimidinone alkynes and 18 new pyrimidinone peptidomimetics were introduced into the chemical space.