Synthesis of β-pyrazinyl-L-alanine (Paa) and of peptide derivatives

The title compound was prepared via a malonic ester synthesis starting with α-chloromethylpyrazine [2], and ending, after an asymmetric enzymatic hydrolysis of the racemic N-acetyl-β-2-pyrazinylalanine to the L -form of the new amino acid. The optical purity was ascertained by ¹H-NMR analysis at 360 MHz of the diastereoisomeric dipeptides L -pyrazinylalanine-L -leucine and D -pyrazinylalanine-L -leucine. Hydrophobic, steric and electronic parameters for its side chain were also estimated, which can be useful for the quantitative study of structure-activity relationships of biologically active peptide derivatives. The new amino acid could be introduced in the place of phenylalanine in the enkephalin-like pentapeptide [D -alanyl², leucine⁵]enkephalin, thus showing good stability towards the classical methods of peptide synthesis.