Method for producing peptide hydrazide, peptide amide, and peptide thioester

Patent metadata

Field	Value
Publication number	US-10053491-B2
Application number	US-201615146589-A
Country	US
Kind code	B2
Filing date	May 4, 2016
Priority date	Nov 5, 2013
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

An object of the present invention is to provide a method for producing a peptide thioester compound, a peptide hydrazide compound, and a peptide amide compound. The present invention provides a method for producing a peptide hydrazide compound or a peptide amide compound by using a compound represented by Formula (2):

wherein R 1 , R 2 , R 3 , and X are as defined in the specification, and using a hydrazine compound or an ammonia compound as a reaction reagent. The present invention also provides a method for producing a peptide thioester compound from the peptide hydrazide compound.

First claim

The invention claimed is:

1. A method for producing a peptide hydrazide compound of Formula (1):

wherein R 1 represents an amino acid residue or a derivative thereof, or a peptide residue or a derivative thereof,
the method comprising:
(A) reacting a compound of Formula (2a) with an alcohol compound in the presence of a transition metal compound comprising a nickel compound, such that an ester compound of Formula (3) is obtained,

wherein R 1 is as defined above,
R 2 represents hydrogen or alkyl,
R 4 represents an arginine side chain, a lysine side chain, or a histidine side chain,
R 5 represents a histidine side chain,
R 6 represents a leucine side chain, an isoleucine side chain, a tyrosine side chain, a phenylalanine side chain, an arginine side chain, or a tryptophan side chain, and
R 7 represents hydroxyl, amino, hydrazino, or an organic group,

wherein R 1 is as defined above, and
R 8 represents alkyl; and
(B) reacting the ester compound of Formula (3) with
a hydrazine compound.

2. The method according to claim 1 , wherein the alcohol compound used in (A) is at least one member selected from the group consisting of methanol, ethanol, and dithiodiethanol.

3. The method according to claim 1 , wherein the transition metal compound further comprises at least one of an iron compound and a palladium compound.

4. The method according to claim 1 , wherein the nickel compound is at least one member selected from the group consisting of nickel chloride, nickel bromide, nickel iodide, and hydrates thereof.

5. The method according to claim 1 , wherein the compound of Formula (2a) is selected from the group consisting of compounds of Formulas (2a-1) to (2a-7):

wherein R 1 and R 7 are as defined above;

wherein R 1 and R 7 are as defined above;

wherein R 1 and R 7 are as defined above;

wherein R 1 and R 7 are as defined above;

wherein R 1 and R 7 are as defined above;

wherein R 1 and R 7 are as defined above; and

wherein R 1 and R 7 are as defined above.

6. The method according to claim 1 , further comprising preparing the compound of Formula (2a) by a biological synthesis process.

7. A method for producing a peptide thioester compound represented by Formula (5):

wherein R 1 represents an amino acid residue or a derivative thereof, or a peptide residue or a derivative thereof, and
R 10 represents optionally substituted alkyl or optionally substituted aryl,
the method comprising:
step (E) of reacting the peptide hydrazide compound represented by Formula (1) obtained in the production method of claim 1 with a nitrite; and
step (F) of reacting an acyl azide compound represented
by Formula (6) obtained in step (E):

wherein R 1 is as defined above,
with a thiol compound.

8. The method for producing a peptide thioester compound according to claim 7 , wherein the starting material compound represented by Formula (2) is prepared using a biological synthesis process.

Assignees

• Ajinomoto Kk

Inventors

• Otaka Akira
• Shigenaga Akira
• Sugiyama Masakazu
• Fujii Hidemi

Classifications

• C07D249/00

  Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• C07K1/107 Primary

  by chemical modification of precursor peptides · CPC title

• C07K1/003

  by transforming the C-terminal amino acid to amides · CPC title