Method for producing peptide compound

Patent metadata

Field	Value
Publication number	US-12528834-B2
Application number	US-202017763185-A
Country	US
Kind code	B2
Filing date	Sep 14, 2020
Priority date	Sep 25, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

An object of the present invention is to provide a method for producing a peptide with high efficiency, and a method for producing a peptide which comprises the following steps (1) and (2): (1) a step of mixing an N-protected amino acid or an N-protected peptide with a carboxylic acid halide represented by the formula (I)(wherein X represents a halogen atom,R1, R2 and R3 each independently represent an aliphatic hydrocarbon group which may have a substituent, and a total number of the carbon atoms in R1, R2 and R3 is 3 to 40); and(2) a step of mixing the product obtained in the step (1) and a C-protected amino acid or a C-protected peptideis provided.

First claim

The invention claimed is:

1 . A method for producing a peptide which comprises the following steps (1) and (2):
(1) a step of mixing an N-protected amino acid or an N-protected peptide with a carboxylic acid halide represented by the formula (II)

wherein
X represents a halogen atom, and
(2) a step of mixing the product obtained in the step (1) with a C-protected amino acid or a C-protected peptide.

2 . The method for producing a peptide according to claim 1 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

3 . The method for producing a peptide according to claim 1 , wherein X is a chlorine atom or a bromine atom.

4 . The method for producing a peptide according to claim 1 , wherein X is a chlorine atom.

5 . The method for producing a peptide according to claim 1 , wherein the amino acid in the N-protected amino acid is an α-amino acid other than glycine.

6 . The method for producing a peptide according to claim 5 , wherein the amino acid in the N-protected amino acid is an α-amino acid other than glycine, and the reactive functional group at a side chain of the amino acid is protected.

7 . The method for producing a peptide according to claim 5 , wherein the α-amino acid other than glycine is valine, phenylalanine, threonine, leucine, tryptophan, serine, cysteine, aspartic acid or tyrosine.

8 . The method for producing a peptide according to claim 1 , wherein the amino acid in the C-protected amino acid or the amino acid in the N-terminal residue of the C-protected peptide is an α-amino acid other than an N-substituted amino acid.

9 . The method for producing a peptide according to claim 1 , wherein the step (2) is a step of mixing the product obtained in the step (1) and a C-protected peptide.

10 . The method for producing a peptide according to claim 1 , wherein the N-terminal protective group of the N-protected amino acid or the N-protected peptide is a carbamate-based protective group.

11 . The method for producing a peptide according to claim 10 , wherein the carbamate-based protective group is a 9-fluorenylmethyloxycarbonyl group or a benzyloxycarbonyl group.

12 . The method for producing a peptide according to claim 3 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

13 . The method for producing a peptide according to claim 4 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

14 . The method for producing a peptide according to claim 5 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

15 . The method for producing a peptide according to claim 6 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

16 . The method for producing a peptide according to claim 7 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

17 . The method for producing a peptide according to claim 8 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

18 . The method for producing a peptide according to claim 9 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

19 . The method for producing a peptide according to claim 10 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

20 . The method for producing a peptide according to claim 11 , which further comprises one or more repetitions of the following steps (3) to (5):
(3) a step of removing a protective group for an N-terminal of the peptide obtained in the step (2) or (5); (4) a step of mixing an N-protected amino acid or an N-protected peptide with the carboxylic acid halide represented by the formula (II); and (5) a step of mixing the product obtained in the step (4) and the product obtained in the step (3).

Assignees

• Nissan Chemical Corp
• Peptidream Inc

Inventors

• Morodome Keisuke
• Handa Michiharu

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07K5/0812

  and aromatic or cycloaliphatic · CPC title

• C07K5/0819

  with the first amino acid being acidic · CPC title

• C07K5/0808

  the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu · CPC title

• C07K5/06113

  Asp- or Asn-amino acid · CPC title