Phosphinamides: a new class of amino protecting groups in peptide synthesis

Abstract

N _α -Diphenylphosphinyl protected α-amino acids have been prepared from the corresponding methyl or benzyl esters using diphenylphosphinic chloride–N-methylmorpholine followed by mild alkaline hydrolysis or catalytic hydrogenolysis, respectively. The suitability of these derivatives for use in amide bond forming reactions and their stability during the customary manipulations of peptide synthesis have been exhaustively examined. Acid-catalysed removal of the diphenylphosphinyl group has also been studied, with the aid of 32.4 MHz ³¹P n.m.r. spectroscopy, and compatability of cleavage with tryptophan and methionine residues—in the absence of scavengers—has been demonstrated by the synthesis of the partially protected C-terminal tetrapeptide of gastrin, Cl^–H₂⁺Trp-Met-Asp(OBu^t)-PheNH₂.