Amino-acids and peptides. Part XXV. The mechanism of the base-catalysed racemisation of the p-nitrophenyl esters of acylpeptides

Abstract

The p-nitrophenyl esters of benzoyl- and benzyloxycarbonyl-glycyl-L-phenylalanine are racemised by triethylamine in dichloromethane much more rapidly than are the analogous esters of benzyloxycarbonyl- and phthaloyl-L-phenylalanine. It is shown that the acyldipeptide esters react reversibly with triethylamine to give the corresponding oxazolone, the equilibrium being greatly in favour of the ester. The racemisation of benzoylglycyl-L-phenylalanine p-nitrophenyl ester by triethylamine is suppressed by the addition of a large excess of the oxazolone derived from benzyloxycarbonylglycylphenylalanine, which, it is suggested, reacts immediately with the p-nitrophenoxide anion and so prevents the back-reaction by which racemic ester is formed. This experiment distinguishes clearly between the “direct exchange” mechanism of racemisation and that through the oxazolone, and it is concluded that such racemisation proceeds through the intermediate formation, racemisation, and coupling of the corresponding oxazolone. Evidence is also given that the conversion of benzyloxycarbonylglycyl-L-phenylalanine into its p-nitrophenyl ester by means of diphenyl-keten is accompanied by racemisation.