Synthesis of e-Aspartyl-lysines and of isoHexylamides of Aspartic Acid

Lockhart & Abraham (1956) found that two compounds which appeared to be aspartyl-lysine and aspartyl(isoleucyl)-lysine respectively were formed when bacitracin A was hydrolysed with 11 Nhydrochloric acid at 800. The aspartic acid residue in these compounds had the L-configuration and was linked to the e-amino group of L-lysine. However, both compounds carried a net positive charge at pH 7 and this raised the question whether they were simple peptides. The synthesis of peptides in which aspartic acid is joined through its mand f,carboxyl group respectively to the e-amino group of lysine has therefore been undertaken. For purposes of comparison the aand f,-i8ohexylamides of aspartic acid have also been synthesized. L-Aspartic acid and L-lysine have been used in this work but no attempt has been made to discover whether significant racemization occurs in the course of any of the reactions. It seemed possible that the reaction of N-benzyloxycarbonyl-L-aspartic anhydride (I) with the copper complex of L-lysine or with x-toluene-psulphonyl-L-lysine ester (a-tosyl-L-lysine ester) would provide a simple route to both e-N-(a-Laspartyl)-L-lysine (II) and e-N-(fi-L-aspartyl)-Llysine (III). The anhydride (I) was used by Bergmann & Zervas (1932) in peptide synthesis and was later shown to yield a mixture of oaand f-aspartyl derivatives on reaction with several amino acid esters (LeQuesne & Young, 1952; John & Young, 1954). C065-CH2-0-CO-NH-CH-CO >0 CH2-CO (I)