A peptide is efficiently produced by reacting a carboxyl group of an amino acid or intermediate peptide in which an amino group is protected, with an alkali metal salt or alkaline earth metal salt of an amino acid in which an amino group is not protected, or of an intermediate peptide in which an N-terminal is not protected, is a two-layer solvent composed of water and a hydrophobic organic solvent.

The present invention provides an improved process for the preparation of high purity glucagon comprising the use of Xmb-protected amino acids, wherein may Xmb include, e.g., 2,4,6-trimethoxybenzyl, 2,4-dimethoxybenzyl, or 2-hydroxy-4-methoxybenzyl. The process also comprises the use of building blocks such as pseudoprolines to avoid aggregation and obtain the product in high yield and purity.

Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing the etelcalcetide includes the following steps: using N-Boc-L-Cqs-OtBu as a starting material to generate a primary product of a formula (A) by means of a substitution reaction, herein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing the etelcalcetide, which may improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.

##STR00001##

It was found that a peptide compound that has an N-substituted-α,α-disubstituted amino acid residue at the N-terminus and containing a dipeptide residue in which the N-substituted-α,α-disubstituted amino acid residue and an N-substituted amino acid residue are linked together, can be efficiently produced by linking an N-unsubstituted-α,α-disubstituted amino acid whose amino group is protected with an electron-withdrawing protecting group to an N-substituted amino acid or a peptide compound having an N-substituted amino acid residue at the N-terminus, and then allowing a substituent-introducing agent to act in the presence of a specific base to selectively introduce a substituent to the amino group at the N-terminus.

Methods for making an arylomycin ring of formula t ##STR00001##
or salts or solvates thereof, wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.5, R.sup.10 and Pg.sup.1 are as defined herein.

An automated system of reactors carries out a solid-phase peptide synthesis, and more particularly a solid-phase peptide synthesizer which is automated, by means of a reactor with a liquid-recirculation loop making it possible to measure, in real time, chemical species in the reactor via measuring cells. This system includes inlet pipes, namely: pipes dedicated to the introduction of resin, pipes dedicated to the introduction of the synthesis and washing solvent, pipes dedicated to the introduction of the agent for deprotecting the amino acid introduced, pipes dedicated to the introduction of the reagents, and includes an assembly reactor and a loop for recirculation of the liquid of the reactor.

A process for synthesizing peptides or proteins or peptidomimetics by successive elongation, with units, of the second end (primary or secondary amine function, hydroxyl function or thiol function) of a peptide or protein or peptidomimetic chain, characterized in that: said units are selected from the group made up of: α, β or γ-amino acids, α, β or γ-hydroxy acids and α, β or γ-mercapto acids (natural or unnatural or synthetic), the molecules having at least two functional groups; —the first end of said peptide or protein or peptidomimetic is bonded by a covalent bond to an anchoring molecule that is soluble in organic solvents such as halogenated solvents (methylene chloride, chloroform), ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, isooctane, cyclohexane, hexane(s), methylcyclohexane or methyl tert-butyl ether, or aromatic solvents such as benzene or toluene, or any other suitable solvent.

A process for synthesizing peptides or proteins or peptidomimetics by successive elongation, with units, of the second end (primary or secondary amine function, hydroxyl function or thiol function) of a peptide or protein or peptidomimetic chain, characterized in that: said units are selected from the group made up of: α, β or γ-amino acids, α, β or γ-hydroxy acids and α, β or γ-mercapto acids (natural or unnatural or synthetic), the molecules having at least two functional groups; —the first end of said peptide or protein or peptidomimetic is bonded by a covalent bond to an anchoring molecule that is soluble in organic solvents such as halogenated solvents (methylene chloride, chloroform), ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, isooctane, cyclohexane, hexane(s), methylcyclohexane or methyl tert-butyl ether, or aromatic solvents such as benzene or toluene, or any other suitable solvent.

The present invention provides processes and compounds for the preparation of glucagon and GLP-1 co-agonist compounds that are useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).

The present invention provides processes and compounds for the preparation of glucagon and GLP-1 co-agonist compounds that are useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).