New methods in peptide synthesis. Part III. Protection of carboxyl group

Abstract

For the protection of the carboxyl group of amino-acids during peptide synthesis, the acid-labile diphenylmethyl ester group was used. N-Trityl-(i.e., triphenylmethyl), N-formyl-, or N-o-nitrophenylsulphenyl-amino-acid diphenylmethyl esters were converted by known methods into the corresponding ester hydrochlorides. The deblocking of the carboxyl group was accomplished either by the action of dilute solutions of hydrogen chloride or hydrogen bromide in nitromethane, by trifluoroacetic acid, or by catalytic hydrogenolysis.

The acid-stable phenacyl ester group permitted the preparation of the corresponding amino-acid ester hydrobromides by treating N-benzyloxycarbonylamino-acid phenacyl esters with hydrogen bromide in acetic acid. Easy alkyl–oxygen ester fission was brought about by sodium thiophenoxide.