Nx-Diphenylphosphinyl protected a-amino acids have been prepared from the corresponding methyl or benzyl esters using dip henyl phosphin ic c hloride-A/-met hylmorp holine followed b y mi Id 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 M H z 3 1 P n.m.r. spectroscopy, and compatability of cleavage with tryptophan and methionine residues-in the absence of scavengers-has been demonstrated b y the synthesis of the partially protected C-terminal tetrapeptide of gastrin, CI-H,+Trp-Met-Asp(0Bu') -PheNH,.:One of the most successful classes of amino protecting groups is that based on the t-butylurethane which may be cleaved by mild acid. Structure variation gives rise to groups susceptible to deprotection over a wide range of acid conditions. A disadvantage of this type of protection is the formation of relatively stable carbenium ions during the deprotection process which can react with the side-chain functionality of cysteine, methionine, tryptophan, or tyrosine leading to alkylated products.2 Similarly, removal of the benzyloxycarbonyl and related groups in the presence of methionine residues under the standard conditions employed in peptide synthesis has incurred serious difficulties.2 For example, the methionine side chain can be demethyiated with sodium in liquid ammonia resulting in the formation of homocysteine and attempts at acidolytic cleavage of the protecting group can result in S-benzylation; the corresponding sulphonium salt, instead of reverting to a methionine derivative is known to decompose to a Sbenzylhomocysteine derivative. Furthermore, reports of the interference of methionine with catalytic hydrogenation because of the poisoning effect of the sulphur atom on the catalyst are legion and although extended reaction times can lead to the desired deprotection, some conversion of methionine into a-aminobutyric acid has been reported to occur.2 Despite the possible inclusion of additives to prevent poisoning of the catalyst or of scavengers, e.g. anisole or thiols, to remove carbenium ions, it was thought desirable to design another series of protecting groups which have the same propensity towards acid cleavage, but which occasion no deleterious side reactions during deprotection. In this respect, surprisingly few amine protecting groups have been developed utilising the well known acid lability of the phosphorust Deceased June 25, 1978 :With the exception of glycine, all a-amino acids are of the Lconfiguration unless otherwise stated and standard abbreviations are used throughout in the formulation of derivatives (IUPAC-IUB Commission on Biochemical Nomenclature, J. B i d . Chem., 1972, 247, 977). In addition, the following undefined abbreviations have been used: Boc t-butyloxycarbonyl; Bpoc 2-biphenyl-4-...
