GB863170A - Improvements in or relating to the production of amido peptides - Google Patents

Abstract

The invention comprises compounds of the general formula: <FORM:0863170/IV (b)/1> and the esters thereof, wherein n is 1, 2 or 3, one of R1 and R2 represent-NH2, the other of R1 and R2 representing the radical of an amido acid or of a peptide which occurs in known di-or poly-peptides, the diethylamine salt of N-trity L-asparaginyl glycine and the benzhydrylamine salt of N-trityl L-asparaginyl L-leucine, and the preparation of compounds (I) by condensing at a temperature below room temperature a mono-amido-N-trityl amino acid of the general formula: <FORM:0863170/IV (b)/2> wherein one of R11 and R12 represent NH2 and the other representing OH, dissolved in an inert solvent, with a non salified amino group-containing amino acid ester in the presence of dicyclohexylcarbo diimide. The invention further comprises a process for the preparation of an amido peptide of the general formula: <FORM:0863170/IV (b)/3> which comprises saponifying, or in suitable cases hydrogenolysing the ester (I) and detritylating the product; or first detritylating the ester (I) and then saponifying or in suitable cases hydrogenolysing the resulting ester; and the intermediate L-asparaginyl S-trityl L-cysteinyl L-prolyl L-leucyl glycine methyl ester. The diethylamine salt of N-trityl asparaginyl glycine is isolated after hydrogenolysis of the benzyl ester in the presence of diethylamine and the benzhydrylamine salt is prepared by reacting the corresponding free acid with the base. N-Trityl asparagine is prepared either by hydrolysis of the trityl ester with pyridine or by hydrogenolysis of the benzyl ester. The diethylamine salt is prepared by hydrogenolysis of N-trityl asparagine trityl ester in the presence of diethylamine and isolating the salt. L-Asparagine benzyl ester is prepared by passing hydrogen chloride through a chloroformic suspension of N-tritylasparagine benzyl ester. Specification 863,171 is referred to.