Amino-acids and peptides. Part XXX. Facilitation of peptide synthesis by the use of 4-picolyl esters for carboxy-group protection

Abstract

The preparation and properties of the dihydrobromides of some 4-picolyl esters of amino-acids (I), and of their benzyloxycarbonyl derivatives, are described. The esters may be cleaved by cold alkali, by catalytic hydrogenation, by sodium in liquid ammonia, and by electrolytic reduction. A new procedure for the facilitation of peptide synthesis is reported, in which the carboxy-terminal residue is incorporated as its 4-picolyl ester; after each coupling reaction the product is separated from the excess of acylating agent, co-products, and by-products by extraction into an acidic phase, e.g. sulphoethyl-Sephadex. The procedure is illustrated by two syntheses of L-leucyl-L-alanylglycyl-L-valine.