Patent GB-770575-A (GB)
Title: Improvements in or relating to peptides
IPC: C07K1/10
Filed: 1955-02-16
Abstract: The invention comprises N-benzyl- or N,N-dibenzyl-peptides and polypeptides of the formula:- <FORM:0770575/IV(b)/1> where A is the grouping <FORM:0770575/IV(b)/2> Y is H or C6H5CH2-, R, R1 and R11 are H, alkyl, aryl, or heterocyclic radicals, they may be identical or different, and R1 and R11 may be hydroxylated, and n, n1, n11 and m are zero or integers up to 8, which may be identical or different, and also comprises a method of making them by reacting a hydrochloride of the chloride of an N-mono- or N,N-dibenzylated amino acid or peptide of the formula:-Z-(A)m1-OH wherein Z is the grouping:- <FORM:0770575/IV(b)/3> with a salt (e.g. an hydrochloride) of an amino acid or peptide whose carboxy group has been protected, using a known method by conversion into an ester, amide, anilide or other easily saponifiable compound, said last-mentioned amino-acid having the formula:-H-(A)m11-Q wherein Q is the grouping <FORM:0770575/IV(b)/4> m1 and m11 being selected from zero and integers in such a way that m1+m11=m.  The invention also comprises the hydrochlorides of N,N-dibenzylglycyl chloride, N-monobenzylglycyl chloride, N-monobenzyl alanyl chloride, N-monobenzyl tryptophyl chloride, N-monobenzyl tryptophane, N - monobenzyl - L - leucyl chloride.  The benzyl groups may be removed from the products by hydrogenolysis and the protected carboxy group is converted to carboxy, by the same hydrogenolysis if the benzyl ester is employed. The hydrochlorides of the chlorides of N-benzylated or N,N-dibenzylated amino acids are prepared from the acids by reaction with phosphorus pentachloride, alone or mixed with acetyl chloride, phosphorus oxychloride, thionyl chloride, or phosphorus trichloride. The N-benzylaminoacids are prepared (a) from benzaldehyde and the aminoacid ester or barium salt, followed by reduction of the Schiff base; (b) partial hydrogenolysis of the N,N-dibenzyl body; (c) hydrolysis of an N-acyl-N-benzylamino acid; (d) resolution of a racemate (e) action of benzylamine on an a -halogenated acid. N,N-dibenzyl acids are prepared by the action of benzyl chloride on the amino-acid.  Examples describe (1) the preparation of the hydrochloride of N,N-dibenzylglycyl chloride, its reaction with glycine ethyl ester to give dibenzylglycylglycine ethyl ester which is saponified, and hydrogenolysis of this or of the benzyl ester to give glycylglycine; (2) the preparation of the hydrochloride of N-benzyl-DL-alanyl chloride, the condensation of this with the hydrochloride of glycine ethyl ester, and saponification to give N - benzyl - DL - alanylglycine, and hydrogenolysis of this to give DL-alanylglycine; (3) the preparation of the hydrochloride of N-benzyl-DL-tryptophyl chloride, condensation of this with glycine ethyl ester hydrochloride and saponification to give N-benzyl-D,L-tryptophylglycine, and hydrogenolysis of this to give DL-tryptophylglycine; (4) the preparation of the hydrochloride of the ethyl ester of glycylglycine and condensation of this with N,N-dibenzyl glycyl chloride hydrochloride, followed by saponification to give N,N-dibenzyldiglycylglycine, which may be partially hydrogenolysed to N-benzyldiglycylglycine; (5) N-benzyldiglycylglycine is similarly prepared, and this or the N,N-dibenzyl derivative is hydrogenolysed to give diglycylglycine; (6) N,N-dibenzyldiglycylglycine is similarly prepared from N,N-dibenzylglycylglycyl chloride and glycine ethyl ester; (7) the preparation of the hydrochloride of N-benzyl-L-leucyl chloride and condensation with L-leucine benzyl ester to give N-benzyl-L-leucyl-L-leucine which is hydrogenolysed to give L-leucyl-L-leucine; (7) the condensation of the hydrochloride of N,N-dibenzylglycyl chloride with DL-serine ethyl ester, followed by hydrolysis to give N1-(N,N-dibenzylglycyl)-serine, which is hydrogenolysed to N-glycyl-DL-serine; (8) the preparation of N-benzyl-DL-serine is also described from benzaldehyde and DL-serine ethyl ester, followed by hydrogenation.