Synthesis and conformational study of novel pyrazine-based pseudopeptides bearing amidoxime, amidoxime ester and 1,2,4-oxadiazole units

An efficient synthesis of pyrazine-based amidoximes bearing amino acid residues is reported. Esterification of amidoximes with further microwave-assisted cyclization into alpha-amino acid-derived 1,2,4-oxadiazoles has been developed. Conformational analysis of the obtained pseudopeptides by NMR and FTIR spectroscopy revealed intramolecular interactions due to the influence of a pyrazine ring and prolyl amide bond isomerization. The content of trans/cis conformers depending on the substitution at the pyrazine moiety for Pro-containing derivatives has been estimated. (C) 2016 Elsevier Ltd. All rights reserved.