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

• Published in: Tetrahedron letters 2014-01, Vol.55 (1), p.227-231
• Main Authors: Balan, Biny, Bahulayan, D.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole; Click chemistry; Dihydropyrimidinones; Multi-component reactions; Solvent free synthesis
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2013.11.002

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.