Synthesis and antioxidant activity of DOPA peptidomimetics by a novel IBX mediated aromatic oxidative functionalization

Abstract

DOPA peptidomimetics with stable O-C and N-C covalent bonds between amino acid residues have been prepared by aromatic oxidative functionalization of tyrosine with 2-iodoxybenzoic acid (IBX). The reaction involves the Michael-like nucleophilic addition of different oxygen and nitrogen protected amino acids on a reactive DOPA quinone intermediate. Similar results were obtained in heterogeneous conditions using supported IBX-amide for more runs. Among the novel derivatives, compounds containing glycine residues showed a more pronounced antioxidant activity in the 2,2-diphenyl picrylhydrazyl (DPPH) radical scavenging cell free assay. Instead, valine derivatives showed the highest biological effect in L5178Y mouse lymphoma cells, by assessing the ability to reduce H<inf>2</inf>O<inf>2</inf> induced DNA breakage in the alkaline comet assay.