Amino-acids and peptides. Part XXXIV. Anchimerically assisted coupling reactions: the use of 2-pyridyl thiolesters

Abstract

Further examples are presented of the use in peptide synthesis of esters for which aminolysis is assisted by a neighbouring group. 2-Pyridyl thiolesters of phthaloyl-, benzyloxycarbonyl-, and t-butoxycarbonyl-amino-acids are described, and it is shown that they condense very rapidly even with hindered amino-esters to give high yields of protected dipeptides. Phthaloyl-L-phenylalanine pyrimidin-2-yl thiolester is also described. No racemisation could be detected when t-butoxycarbonyl-L-valine 2-pyridyl thiolester condensed with L-valine methyl ester, even in the presence of triethylamine. The thiolesters reacted slowly with alcohols, and ethyl O-t-butoxycarbonylglycylglycolate and -DL-lactate were so prepared. In contrast to the usual solvent dependence for the aminolysis of active esters, the rate of condensation of t-butoxycarbonyl-L-leucine 2-pyridyl thiolester with p-anisidine increases when the solvent is changed from dimethyl sulphoxide to dimethylformamide and then to dioxan or ethyl acetate.