PROCESS FOR THE MANUFACTURE OF TYROSINE-CONTAINING PEPTIDES AND THE DERIVATIVES THEREOF

摘要

1,201,121. Tyrosine containing derivatives. FARBWERKE HOECHST A.G. 1 March, 1968 [2 March, 1967; 7 July, 1967], No. 10099/68. Heading C2C. A process for the manufacture of tyrosinecontaining peptides, wherein a novel peptide containing at least one tyrosine unit of formula in which R is alkoxy derived from a primary or secondary alcohol, an aralkoxy radical containing at least 2 carbon atoms between the phenyl group and the oxygen atom or an -NHR 1 group in which R 1 is H, alkyl, aralkyl or aryl, is (a) subjected to alkaline hydrolysis or (b) treated with (i) an alkali metal alcoholate, (ii) a solution of an alkali or alkaline earth metal in liquid ammonia or (iii) ammonia, an amine, a hydrazine or, when R 1 is not -NHR 1 , a monoacyl-hydrazine, the amine or hydrazine derivative containing at least one NH group. Tyrosine derivatives of general formulµ in which R is C 1-4 alkoxy, Ac is carbobenzoxy or t-butyloxycarbonyl or in II may be formyl and R 1 is H, isobutyl, phenyl or 4-nitrophenyl are claimed per se. Intermediates isolated are CBO-tyr (EtOC)- OPNP; H-tyr(AC)-OCH 3 .HCl, H-tyr(i-BAC)- OCH 3 .HBr; H-tyr(PAC)-OCH 3 .HBr; and BOC-tyr(PAC)-OTCP. (CBO = carbobenzoxy, BOC = t-butyl-oxycarbonyl, EtOC = ethoxycarbonyl, AC = carbamyl, PNP =p-nitro-phenyl, i-BAC = isobutyl-carbamyl, PAC = phenylcarbamyl, and TCP = 2,4,5-trichlorophenyl). Pharmaceutical compositions comprise a peptide when prepared by the above method together with a suitable excipient.