Patent GB-1000898-A (GB)
Title: Peptide derivatives and a process for the manufacture of same
IPC: C07K5/04
Filed: 1963-10-09
Abstract: The invention comprises compounds of the general formula <FORM:1000898/C2/1> wherein n1 and n2 each represent 0 or 1, X represents a hydroxy, alkoxy, amino, alkylamino, dialkyl-amino or hydriazino group and each R is the residue of an a -amino carboxylic acid devoid of its a -amino and carboxylic groups (at least one such residue carrying an amino or a guanidino group) and wherein the molecule contains at least one long-chain (i.e. at least 8 C in the said chain) alkoxy carbonyl or alkenyloxycarbonyl residue on an amino group, their acid addition salts and the preparation thereof by condensing a compound of the formula <FORM:1000898/C2/2> with a compound of the formula <FORM:1000898/C2/3> wherein a, b, c and d each represent 0 or 1 but which total 0, 1 or 2, Y represents a halogen atom or a hydroxy, azido, phenoxy nitrophenoxy or phenyl mercapto group or the residue of an anhydride with an inorganic or organic acid, X1 represents an alkoxy, amino, alkylamino or dialkyl-amino group or a hydroxy group in the form of a salt with an inorganic or tertiary organic base and all amino groups with the exception of that involved in the condensation with the residue Y being protected by removable protecting groups and/or long chain alkoxy-carbonyl or alkenyloxy carbonyl groups, with the splitting off of the compound H-Y so as to form a dipeptide, tripeptide or tetrapeptide in which all amino groups are protected, converting those peptides which do not contain any long-chain N-alkoxycarbonyl or N-alkenyloxycarbonyl substituents into the corresponding peptide carrying such long chain groups by exchange of selectively removable protecting groups for at least one long chain alkoxycarbonyl or alkenyloxycarbonyl group, converting the resulting products into a hydrazide if necessary, splitting off the removable protecting groups from the resulting peptide and, if desired, converting the products into acid addition salts.  The starting materials may be derived from D, L- or DL-serine, phenylalanine, tyrosine, leucine, lysine, arginine, ornithine, a ,g -diamino butyric acid and a ,b -diamino-propionic acid.  Na  - Cetyloxycarbonyl - (Ne  - benzyloxycarbonyl) - L - lysine is prepared from cetyloxycarbonyl chloride (from cetyl alcohol and phosgene) and Ne -benzyloxycarbonyl-L-lysine.  Similarly is prepared Na -lauryloxycarbonyl-(Ng -benzyloxycarbonyl) - D - a ,g  - diaminobutyric acid and lauryloxycarbonyl chloride. Na -Octyloxycarbonyl - (Nd ) - benzyloxycarbonyl) - L-ornithine hydriazide is prepared by reacting Nd  - benzyloxycarbonyl - L - ornithine methyl ester with phosgene to give carbonyl-(Nd -benzyloxycarbonyl) - L - ornithine methyl ester then with n-octanol to give Na -octyloxycarbonyl-(Nd -benzyloxy carbonyl)-L-ornithine methyl ester and then with hydriazine.  Pharmaceutical compositions having anti-bacterial activity comprise the compounds of the invention together with a liquid or solid inorganic or organic carrier.  The preparations may be in the form of tablets, dragees, capsules, suppositories, solutions, suspensions or emulsions. The compounds are also useful as occidiostats and may be intermixed with animal feeds or feedstuffs intended for ingestion by animals (e.g. fowl).