Amino Acids and Peptides. V. The Alkaline saponification of N-Benzyloxycarbonyl peptide esters

In the alkaline saponification at room temperature of six N-benzyloxycarbonyl peptide esters (I) different products were obtained depending on the amount of alkali employed. When 1 mole of alkali was used, all the esters gave the corresponding acids, although with benzyloxycarbonylglycyl-S-benzyl-L-cysteine ethyl ester some racemization occurred. With 2 moles of alkali, benzyl alcohol was eliminated from the benzyloxycarbonyl group in all esters where a glycine residue was next to the N-terminal residue, thereby forming either the corresponding urea derivative (III) or the hydantoin-3-acetic acid derivative (II). Excess alkali caused no similar rearrangement in other sequences under these conditions. The need for special care in saponifying certain N-benzyloxycarbonyl peptide sequences is indicated. An improvement in the tetraethyl pyrophosphite procedure for the synthesis of peptides is described.