Mild and Biocompatible Synthesis of Highly Symmetrical Tetrasubstituted Pyrazines from Amino acids and Peptides: A Novel Strategy for the Self-Stapling of Peptides

Abstract

The utility of unnatural amino acids has been extensively explored in the construction of new building blocks, molecular scaffolds, and therapeutic leads. For instance, highly versatile g-amino -keto acids present in several biologically active peptides, has been used as precursor for the synthesis of many biologically relevant molecules such as statines, ketomethylene dipeptide isosteres, -lactams, tricarbonyl compounds, rhodopeptins, substituted pyridines, fluorescent amino acid tags, cholecystokinin receptor antagonists, g-amino , -unsaturated esters, and -azo -carbonyl compounds. Here we are demonstrating the utility of -keto-g-amino ester in the synthesis of highly symmetrical tetrasubstituted pyrazines through simple aerial oxidation. In addition we also exploited this mild and biocompatible protocol for the selfstapling of peptides. The easy synthesis, mild and biocompatible aromatization of the - keto-g-amino esters and peptide -keto-esters may find application in biological and medicinal chemistry as well as in material science.