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.

Provided is an alkyldiphenylmethane protective agent, which can prevent solidification or insolubilization of a compound by protecting a functional group of the compound to achieve easy separation and purification after a reaction. An alkyldiphenylmethane compound represented by general formula (1): ##STR00001## wherein Y represents —OR.sup.19 (wherein R.sup.19 represents a hydrogen atom or an active ester-type protecting group), —NHR.sup.20 (wherein R.sup.20 represents a hydrogen atom, a C.sub.1-6 linear or branched alkyl group, or an aralkyl group), isocyanate group, an azide group, or a halogen atom, Z represents a C.sub.1-4 linear or branched alkyl group, an alkenyl group, or a cycloalkyl group, at least one of R.sup.1 to R.sup.10 represents a group represented by formula (2):
—O—R.sup.11—X-A  (2) and the others each independently represent a hydrogen atom, a halogen atom, a C.sub.1-4 alkyl group, or a C.sub.1-4 alkoxy group; R.sup.11 represents a C.sub.1-16 linear or branched alkylene group; X represents O or CONR.sup.21 (wherein R.sup.21 represents a hydrogen atom or a C.sub.1-4 alkyl group); and A represents, for example, a group represented by formula (3): ##STR00002## wherein R.sup.12, R.sup.13, and R.sup.14 may be the same or different and each independently represent a C.sub.1-6 linear or branched alkyl group or an optionally substituted aryl group; R.sup.15 represents a single bond or a C.sub.1-3 linear or branched alkylene group; and R.sup.16, R.sup.17, and R.sup.18 each independently represent a C.sub.1-3 linear or branched alkylene group.

The purpose of the present invention is to provide a protecting group which improves the solubility of a compound having a functional group protected with the protecting group in an organic solvent and which is easily separated and purified after a reaction with avoiding solidification or insolubilization. Provided is a benzyl compound represented by Formula (1) where X.sup.1 represents —CH.sub.2OR.sup.14 (where R.sup.14 represents a hydrogen atom, a halogenocarbonyl group, or an active ester-type protecting group), —CH.sub.2NHR.sup.5 (where R.sup.15 represents a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or an aralkyl group), a halogenomethyl group, a methyl azide group, a formyl group, or an oxime; and at least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 is a group represented by Formula (2), and the remainders each represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms, where R.sup.6 represents a linear or branched alkylene group having 1 to 16 carbon atoms; X.sup.2 represents O or CONR.sup.16 (where R.sup.16 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms); and A represents a group represented by Formula (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), or (13).

The present disclosure relates to site-selective labeling compounds, and methods of using such compounds.

The invention provides a method for producing a peptide by (1) removing the N-terminal protective group of an amino acid or peptide compound of formula (I):

##STR00001##

wherein Y represents a residue of an N-protected amino acid or an N-protected peptide, and each of R.sup.1, R.sup.2, and R.sup.3 independently represents an aliphatic hydrocarbon group which may have a substituent or an aromatic hydrocarbon group which may have a substituent, wherein the total number of carbon atoms in the R.sup.1R.sup.2R.sup.3Si group is 18 to 80, and the R.sup.1R.sup.2R.sup.3SiCH.sub.2CH.sub.2 group is bonded to the C-terminus of the amino acid or peptide residue in Y; and (2) causing condensation of an N-protected amino acid or an N-protected peptide and the N-terminus of the C-protected amino acid or C-protected peptide obtained in the step (1).

The present disclosure provides a method of solid-phase peptide synthesis from the N terminus to C terminus without detectable epimerization of the C-terminal amino acid. The method includes using derivatized amino acids comprising a diamino-aryl group.

The present invention provides a process for the manufacture of GLP-1 analogues with high yield and purity by fragment condensation on the solid phase. In particular, it describes a convergent synthesis by condensation of a C-terminal pseudoproline fragment A with a fragment B bound to a solid support, followed by deprotection and cleavage from the support and final purification to yield the desired peptide. The invention further provides intermediates useful in the manufacturing process.

The present invention relates to a process for the preparation of Plecanatide, which comprises preparation of three fragments such as Fragment A (7 amino acids), Fragment B (3 amino acids), Fragment D (6 amino acids) and coupling the fragments to provide Plecanatide followed by purification using buffer system comprising Tris hydrochloride (or) Triethylammonium phosphate.

The present invention provides a process for the manufacture of GLP-1 analogues with high yield and purity by fragment condensation on the solid phase. In particular, it describes a convergent synthesis by condensation of a C-terminal pseudoproline fragment A with a fragment B bound to a solid support, followed by deprotection and cleavage from the support and final purification to yield the desired peptide. The invention further provides intermediates useful in the manufacturing process.

Provided are a method for producing a peptide compound including a step of using an aromatic heterocyclic compound represented by Formula (1) represented by Formula (1); a protective group-forming reagent including the compound; and the compound. In Formula (1), a ring A represents an aromatic heterocyclic ring, Y.sup.A's each independently represent —OH, —NHR, —SH, or —X.sup.0, where X.sup.0 represents Cl, Br, or I, R.sup.A and R.sup.C each independently represent an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, R.sup.Bs' each independently represent a monovalent aliphatic hydrocarbon group, a (1+c)-valent aromatic group, or a (1+c)-valent heteroaromatic group, where, in a case where both a and c is 0, R.sup.B is a monovalent aliphatic hydrocarbon group, and the number of carbon atoms in at least one aliphatic hydrocarbon group of R.sup.A, R.sup.B, or R.sup.C is 12 or more.

##STR00001##