Provided are a method for producing a peptide compound including a step of using an aromatic heterocyclic compound 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##

Provided is a method for producing an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof, the method comprising an alkylation step of mixing a starting amino acid or an ester thereof or a peptide containing the starting amino acid or an ester thereof, a C.sub.1-C.sub.6 primary alkylating agent or a substituted methyl halide, and a catalyst in a solvent in the presence of hydrogen, wherein the alkylation step is carried out at a pressure of 1 atm or more, and produces an N-monoalkylamino acid or an ester thereof or a peptide containing the N-monoalkylamino acid or an ester thereof in which a primary alkyl group corresponding to the C.sub.1-C.sub.6 primary alkylating agent or the substituted methyl halide is attached to an amino group of the starting amino acid or an ester thereof.

Peptides may be continuously produced by a method including the following steps (1), (A), (2), and (B): (1) performing a condensation reaction in a flow reactor to obtain an N-protected C-protected peptide in which an N-terminal amino group and C-terminal are protected by protecting groups, a side chain functional group is optionally further protected by a protecting group, and at least one of the C-terminal or the side chain functional group is protected by a pseudo-solid-phase protecting group (N-protected C-protected peptide), (A) washing a reaction mixture containing an N-protected C-protected peptide in a flow reactor and separating oil and water to separate an organic layer containing the N-protected C-protected peptide, (2) subjecting an organic layer containing an N-protected C-protected peptide to a reaction to remove a protecting group of an N-terminal amino group in a flow reactor to obtain a C-protected peptide in which an N-terminal amino group is not protected, C-terminal is protected by a protecting group, a side chain functional group is optionally further protected by a protecting group, and at least one of the C-terminal or the side chain functional group is protected by a pseudo-solid-phase protecting group (N-unprotected C-protected peptide), (B) subjecting a reaction mixture containing an N-unprotected C-protected peptide to washing and oil-water separation in a flow reactor to separate an organic layer containing the N-unprotected C-protected peptide.

Provided are a method for producing a peptide compound including a step of using a condensed polycyclic aromatic hydrocarbon compound represented by Formula (1); a protective group-forming reagent including the compound; and the compound. In Formula (1), a ring A represents a condensed polycyclic aromatic hydrocarbon ring, Y.sup.A's each independently represent CH.sub.2OH, CH.sub.2NHR, CH.sub.2SH, or CH.sub.2X.sup.0, where R represents a hydrogen atom, an alkyl group, or an aralkyl group, and X.sup.0 represents Cl, Br, or I, k represents an integer of 1 to 5, n represents 1 or 2, and R.sup.A's each independently represent an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group. ##STR00001##

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 discloses a method for synthesizing an amide and/or a polypeptide using a transient protected amino acid as an ammonia component. In this method, an allenone compound is used as a condensing reagent, and a silylation reagent is used to temporarily protect the carboxyl of an amino acid or peptide fragment with amino and carboxyl groups both unprotected first. Then after forming an amide bond with another molecular carboxylic acid or amino acid or -carbonyl alkenyl ester derivative of the C-terminal carboxyl of the polypeptide, the temporarily protected carboxyl is deprotected on site under an acidic condition to obtain a target carboxylic acid product and to cyclicly build new peptide bonds.

In various aspects, the present disclosure provides methods for forming radiopaque peptides that comprise one or more iodinated amino acid residues and one or more amine-based amino acid residues. Typically, the peptides contain from 3 to 20 amino acid residues. The present disclosure relates to methods of forming such radiopaque peptides, to the use of such radiopaque peptides as crosslinking agents for forming hydrogels, and to hydrogels formed from such radiopaque peptides. The radiopaque peptides and hydrogels are useful, for example, in various medical applications.

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.