Sanofi

Institut National De La Sante Et De La Recherche Medicale

C M Industries

Joseph Diaz

Henri Demarne

Romeo Roncucci

Paul-Henry Schmelck

Remy Guegan

Pierre Corvol

Jean-Pierre Gagnol

Catherine Cazaubon

Genevieve Evin

Bernard Castro

A process for the synthesis, in liquid phase and by fragments, of hGRF 1-44 and hGRF 1-40. This process consists in coupling, one after the other and in the order of the sequence of the GRF,

Synthesis of hGRF (Somatocrinin) in liquid phase and intermediate

Synthesis of hGRF (somatocrinin) in liquid phase and intermediate

The invention relates to synthesis of hpGRF (Somatocrinin) in liquid phase and to intermediate peptides, comprising: coupling, one after the other and in the order of the sequence of the GRF, the fragments in which: (a) the side acid functions of the aspartic and glutamic acids and the side amine function of the lysine are protected by protector groups stable in the conditions of deprotection of the group Boc, (b) the guanidine function of the arginine is protected by protonation, and (c) the N-terminal amino acid is protected on the amine by the Boc group; selectively eliminating the group Boc from the N-terminal amine of the peptide in phase of elongation by hydrolysis with trifluoroacetic acid, said coupling being effected in an aprotic polar solvent and eliminating, at the end of sequence, all the protector groups by hydrolysis with the aid of a 0.1 to 1M solution of methanesulfonic or trifluoromethanesulfonic acid in trifluoroacetic acid.

Synthesis of hpGRF(Somatocrinin) in liquid phase and intermediate

The invention relates to synthesis of hpGRF (Somatocrinin) in liquid phase and to intermediate peptides, comprising:--coupling, one after the other and in the order of the sequence of the GRF, the fragments in which: (a) the side acid functions of the aspartic and glutamic acids and the side amine function of the lysine are protected by protector groups stable in the conditions of deprotection of the group Boc, (b) the guanidine function of the arginine is protected by protonation, and (c) the N-terminal amino acid is protected on the amine by the Boc group;--selectively eliminating the group Boc from the N-terminal amine of the peptide in phase of elongation by hydrolysis with trifluoroacetic acid, said coupling being effected in an aprotic polar solvent and--eliminating, at the end of sequence, all the protector groups by hydrolysis with the aid of a 0.1 to 1M solution of methanesulfonic or trifluoromethanesulfonic acid in trifluoroacetic acid.

Synthesis of hpGRF (Somatocrinin) in liquid phase and intermediate

The present invention relates to peptide derivatives of the general formula:

Acid-protease inhibiting peptide derivatives

The present invention relates to a new process for the stepwise preparation of somatostatin enabling a product of high purity to be obtained, with high yields, from cysteine in 14 position whose acid function is protected by the phenylazobenzylsulfonylethyloxy group and thiol function is protected by the acetamidomethyl group, all the peptide coupling reactions being effected in liquid phase in the dimethylformamide, the intermediate peptides being precipitated by addition of a second solvent and purified in solid phase by washing with the aid of suitable solvents dissolving the impurities.

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Perols, France

Joseph Diaz