Patent GB-812542-A (GB)
Title: N-benzylpeptides and process for their production
IPC: C07K1/06
Filed: 1955-07-11
Abstract: N,N - dibenzylpeptides or N,N - dibenzylpolypeptides of the general formula: <FORM:0812542/IV (b)/1> in which A is the grouping <FORM:0812542/IV (b)/2> R is M, alkyl, aryl or a heterocyclic radica 1, R1 is H, alkyl, aryl or a heterocyclic radical which may be identical with or different from R, with the proviso that R1 may be hydroxylated, R11 is H, alkyl, aryl, or a heterocyclic radical which may be identical with or different from R and/or R1, with the provisio that R11 may be hydroxylated, R111 is H, alkyl, aryl, or other cyclic radical with the proviso that R111 may be hydroxylated, and n, n1, n11 and m are each zero or an integer from 1-8, are prepared reacting a mixed anhydride of an alkyl carbonic acid and an amino acid or a peptide dibenzylated at the nitrogen atom with an amino acid or a peptide whose carboxy group has been protected by conversion into an ester, amide, or anilide, and saponifying the N,N-dibenzylated peptide so obtained so as to liberate the carboxy group, with the proviso that when m is other than zero one or both said starting materials shall be peptide derivatives. Preferably the carboxy group is protected by esterification, and the peptide ester resulting is purified by dissolution in an organic solvent before saponification.  Also, the aminoacid ester may be used in the form of its hydrochloride, in presence of a tertiary base, and the peptide ester may be purified as hydrochloride by dissolution in an organic solvent.  The ester of the amino-acid or peptide may be the benzyl ester.  The mixed anhydrides are obtained by the action of an alkyl chloroformate in solution in an organic solvent free from hydroxy groups on a solution in a similar solvent of the N,N-dibenzylated aminoacid or peptide, in presence of a tertiary base, said solvent may be chloroform, dichlorethane, tetrahydrofuran or dioxane and said tertiary base may be triethylamine, pyridine, or methylethylpyridine. In examples, the substances (a) below are each reacted with ethyl chloroformate in chloroform in presence of triethylamine to give the mixed anhydrides, which are each reacted with the corresponding substance (b) to give substance (c), which is then subjected to saponification and hydrogenolysis to split off the alkyl and benzyl groups: (1) (a) dibenzylglycine, (b) ethyl glycinate, (c) ethyl N,N-dibenzylglycylglycinate, (2) (a) dibenzylglycine, (b) ethyl ester of DL-valine, (c) N,N-dibenzylglycyl-DL-valine ethyl ester, (3) (a) dibenzylglycine, (b) the ethyl ester of DL-serine, (c) N1-(N,N-dibenzylglycyl)-DL-serine ethyl ester, (4) (a) dibenzylglycine, (b) diethyl-L-glutamate, (c) diethyl N,N-dibenzylglycyl-L-glutamate, (5) (a) dibenzylglycine, (b) tryptophane methyl ester, (c) N,N-dibenzylglycyl-DL-tryptophane, (6) (a) N,N-dibenzyl-DL-alanine, (b) ethyl ester of DL-a -aminobutyric acid, (c) ethyl-N1-(N,N-dibenzyl-DL - a  - alanyl) - DL - a  - aminobutyrate, (7) (a) N,N-dibenzyl-DL-a -alanine, (b) methyl ester of DL-tryptophane, (c) methyl ester of N1 - (N,N - dibenzyl - DL - a - alanyl) - DL - tryptophane, (8) (a) N,N-dibenzyl-DL-a -aminobutyric acid, (b) ethyl glycinate, (c) N1-(N,N-dibenzyl - DL - a  - aminobutyryl) - glycine, (9) (a) N,N-dibenzyl-DL-a -aminobutyric acid, (b) DL-a -aminobutyric acid ethyl ester, (c) ethyl - N1 - (N,N - dibenzyl - DL - a  - aminobutyryl) - DL - a  - aminobutyrate, (10) (a) N,N - dibenzyl - DL - a  - aminobutyric acid, (b) methyl ester of DL-tryptophane, (c) methyl ester of N,N-dibenzyl-DL-a -aminobutyltryptophane, (11) (a) N,N-dibenzyl-DL-norvaline, (b) methyl ester of tryptophane, (c) methyl ester of N1 - (N,N - dibenzyl - norvalyl) - DL - tryptophane, (12) (a) N,N-dibenzyl-leucine, (b) methyl ester of DL-tryptophane, (c) methyl ester of N1-(N,N - dibenzyl - DL - leucyl) - DL - tryptophane, (13) (a) N1-(N,N-dibenzyl-DL-a -alanyl)-tryptophane, (b) ethyl D.L-a -aminobutyrate, (c) N1 - (N,N - dibenzyl - DL - a  - alanyl - DL-tryptophyl) - DL - a  - aminobutyric acid. Specifications 770,575 and 812,541 are referred to.