The use of 2,4,6-trimethylbenzyl esters in peptide synthesis

Abstract

Model experiments with the 2,4,6-trimethylbenzyl esters of N-acylamino acids have shown that this ester group is cleaved by hydrogen bromide in acetic acid under reaction conditions which do not affect benzyl esters appreciably, but which result in removal of benzyloxycarbonyl amino-protecting groups. 2,4,6-Trimethyl- benzyl esters, however, are unaffected by methanolic hydrogen chloride under the conditions used to cleave o-nitrophenylsulphenyl and trityl protecting groups. These selective differences have been utilized for the synthesis of various benzyloxycarbonyl peptide 2,4,6-trimethylbenzyl esters up to the hexapeptide level. Some of these derivatives have been converted into the corresponding free peptides by the action of hydrogen bromide in acetic acid. The 2,4,6-trimethylbenzyl group is more readily cleaved by hydrogen bromide than p-nitrobenzyloxycarbonyl and the possible application of this situation to peptide synthesis is considered.