Amino-acids and peptides. Part XXVIII. Anchimeric acceleration of the aminolysis of esters. The use of mono-esters of catechol in peptide synthesis

Abstract

The hypothesis that the aminolysis of esters can be accelerated by a neighbouring group capable of hydrogen-bonding to the incoming amine and accepting a proton from it has been supported by further evidence. Since such acceleration is not available for oxazolone formation (in which the nucleophile bears no hydrogen) it becomes possible to design fast, racemisation-free methods of peptide synthesis. Phthaloylglycine o-hydroxyphenyl and 4,5-dichloro-2-hydroxyphenyl esters, and benzoyl-L-leucine o-hydroxyphenyl ester, couple rapidly with glycine ethyl ester at room temperature; in the last case (a standard racemisation test) no racemate was found, and with triethylamine the ester gave no oxazolone. When the neighbouring hydroxy-group was protected as the benzyl ether, an unreactive intermediate was obtained which could be activated at will by removal of the benzyl group, by catalytic hydrogenation or by the action of hydrogen bromide in acetic acid.