Patent GB-1049008-A (GB)
Title: Process for the preparation of sulphur-free peptides and of their derivatives
IPC: C07K5/06
Filed: 1965-08-13
Abstract: In processes for producing sulphur-free peptides and their derivatives in which an amino group is protected by conversion into a substituted phenylsulphenyl or triphenyl-methylsulphenyl derivative, the protecting group is split off by treating the peptide or peptide derivative in solution with a Raney metal, e.g. Raney nickel, cobalt, iron or copper. The treatment may be effected by running a solution of the peptide or peptide derivative in an organic or aqueous-organic solvent through a column of Raney metal, or by stirring a solution of the peptide or derivative with the metal.  Examples are given in which (1) o- (or p) - nitrophenylsulphenyl - L - alanyl - L - threonine methyl ester (prepared from o- (or p)-nitrophenylsulphenyl - L - alanine and L-threonine methyl ester by means of dicyclohexyl carbodiimide) yields L-alanyl-L-threonine methyl ester, which may then be reacted with carbobenzoxy - L - proline - N - hydroxysuccinimide ester to yield carbobenzoxy-L-prolyl - L - alanyl - L - threonine methyl ester; (2) L - alanyl - L - threonine methyl ester, prepared as in Example 1, is treated with o-nitrophenylsulphenyl - L - proline - N - hydroxysuccinimide ester (prepared from o-nitrophenylsulphenyl - L - proline and N - hydroxysuccinimide by means of dicyclohexyl carbodiimide) to yield o-nitrophenylsulphenyl - L - prolyl - L - alanyl - L - threonine methyl ester; (3) o - nitrophenylsulphenyl - L - prolyl - L - alanyl-L-threonine methyl ester (see preceding example) yields L - prolyl - L - alanyl - L - threonine methyl ester, which may be further treated with o - nitrophenysulphenyl - glycine - N - hydroxysuccinimide ester (prepared from o-nitrophenylsulphenyl glycine and N-hydroxysuccinimide ester by means of dicyclohexyl carbodiimide to yield o-nitrophenylsulphenylglycyl - L - prolyl - L - alanyl - L - threonine methyl ester; (4) o - nitrophenylsulphenyl - L - alanyl - O - tert. - butyl - L - serine - tert.-butyl ester (prepared from o-nitrophenylsulphenyl - L - alanine and O - tert. - butyl-L-serine-tert.-butyl ester by means of dicyclohexyl carbodiimide) yields L-alanyl-O-tert.-butyl - L - serine - tert. - butyl ester, which may be further treated with o-nitrophenylsulphenyl - L - proline - N - hydroxysuccinimide to yield o-nitrophenylsulphenyl-L-prolyl-L-alanyl - O - tert. - butyl - L - serine - tert. - butyl ester; (5) o-nitrophenylsulphenyl-L-alanyl-O-tert. - butyl - L - threonine - tert. - butyl ester (prepared from o-nitrophenylsulphenyl-L-alanine and O - tert. - butyl - L - threonine - tert.-butyl ester) yields L-alanyl - O - tert. - butyl - L - threonine - tert. - butyl ester, which may be further treated with o-nitrophenylsulphenyl-L-proline - N - hydroxysuccinimide ester to yield o - nitrophenylsulphenyl - L - prolyl - L - alanyl - O - tert. - butyl - L - threonine - test. - butyl ester; (6) o - nitrophenylsulphenyl - L - valyl - L - glutamyl - g  - tert. - butyl ester - L - alanine-tert. - butoxycarbonyl hydrazine (prepared from o - nitrophenylsulphenyl - L - valine - N - hydroxysuccinimide ester [which, in turn, is prepared from o-nitrophenylsulphenyl-L-valine and N-hyroxysuccinimide by means of dicyclohexyl carbodiimide] and L - glutamyl - g  - tert. - butyl ester - L - alanine - tert. - butyloxycarbonyl hydrazine) yields L - valyl - L - glutamyl - g  - tert. - butyl ester - L - alanine - tert.-butyloxycarbonyl hydrazide which may be treated with carbobenzoxy - L - leucine - N - hydroxysuccinimide ester to yield carbobenzoxy-L-leucyl - L - valyl - L - glutamyl - g  - tert. - butyl ester - L - alanine - tert. - butyloxy - carbonyl hydrazide; (7) triphenylmethylsulphenyl - L -phenylalanyl-glycine ethyl ester yields L-phenylalanyl - glycine - ethyl ester, the hydrobromide of which is described; (8) o-nitro-phenylsulphenyl - L - glutaminyl - L - leucine methyl ester (prepared from o-nitrophenylsulphenyl - L - glutamine - N - hydroxysuccinimide ester and L-leucine methyl ester) yields L - glutaminyl - L - leucine methyl ester, which may be treated with carbobenzoxy-O-benzyl- L - tyrosine - p - nitrophenyl ester to yield carbobenzoxy - O - benzyl - L - tyrosyl - L - glutaminyl-L-leucine methyl ester; (9) 2,4,5-trichlorophenylsulphenyl - L - alanyl - L - threonine methyl ester (prepared from 2,4,5-trichlorophenylsulphenyl chloride and L-alanyl-L-threonine methyl ester) yields the product of Example 1; (10) o-nitrophenyl - sulphenyl-D,L - C - phenylglycylglycine ethyl ester (prepared from o-nitrophenylsulphenyl-D,L-C-phenylglycine and glycine ethyl ester by means of dicyclohexyl carbodiimide) yields D,L - C - phenylglycylglycine ethyl ester, the hydrobromide of which is described; (11) o-nitrophenylsulphenyl - p - aminobenzoyl - L - prolyl - L-alanyl - L - threonine methyl ester (prepared from o - nitrophenylsulphenyl - p - aminobenzoic acid - N - hydroxysuccinimide ester and L - prolyl - L - alanyl - L - threonine methyl ester (Example 3) yields p-aminobenzoyl - L - prolyl - L - alanyl - L - threonine methyl ester, which may be hydrolysed to yield p - amino - benzoyl - L - prolyl - L - alanyl L - threonine.