Synthesis of peptide oxazolones and related compounds

Two optically active, crystalline, peptide oxazolones, 2-(1′-benzyloxycarbonylamino-1′-methyl)ethyl-4-methyl-oxazolone and 2-(1′-benzyloxycarbonylamino-1′-methyl)ethyl-4-benzyloxazolone, were prepared and characterized. the imidazole-acceleratedp-nitrophenyl-active ester synthesis was found to be a good route to the dipeptides benzyloxycarbonylaminoisobutyryl-l-phenylalanine methyl ester and benzyloxycarbonylaminoisobutyryl-l-alanine methyl ester. The acids were obtained by careful hydrolysis of these esters with dilute acid, and underwent ring closure, yielding oxazolones on reacting with acetic anhydride or dicyclohexyl-carbodiimide.The synthetic pathways leading to these compounds involved some interesting chemistry of hindered peptides. It was found that the crystalline mixed anhydride of benzyloxycarbonyl-aminoisobutyric and pivalic acids rearranges on heating to give the symmetrical anhydride of benzyloxycarbonylaminoisobutyric acid.