Deprotection method

Patent metadata

Field	Value
Publication number	US-10442834-B2
Application number	US-201514873517-A
Country	US
Kind code	B2
Filing date	Oct 2, 2015
Priority date	Apr 4, 2013
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present invention provides a method of efficiently deprotecting a protected organic compound by catalytic hydrogenation. Specifically, the present invention provides a method of deprotecting an organic compound having at least one functional group selected from the group consisting of a carboxy group, an amino group and a hydroxy group, which is protected by a protecting group represented by the formula (I):

R 1 —C(R 2 )(R 3 )-L 1 -  (I)

[wherein R 1 is an aryl group optionally having substituent(s), R 2 and R 3 are each independently, a hydrogen atom or an aryl group optionally having substituent(s), and L 1 is a single bond, —O—CO— or —O—CH 2 —], comprising hydrogenation in the presence of a metal catalyst and halogenated acetic acid.

First claim

The invention claimed is:

1. A method of producing a sulfur-containing peptide, comprising:
(a) reacting:
(i) a free amino group of an amino acid having a carboxy group protected by a protecting group or a first peptide having a C-terminus protected by a protecting group with
(ii) a free carboxy group of an amino acid having an amino group protected by a protecting group to obtain a second peptide; and

(b) deprotecting any C-terminus and N-terminus, which are protected by a protecting group, of said second peptide, to obtain said sulfur-containing peptide,
wherein said second peptide contains at least one functional group selected from the group consisting of a carboxy group, an amino group, and a hydroxy group, which is protected by a protecting group represented by formula (I):
R 1 —C(R 2 )(R 3 )-L 1 -  (I)

wherein R 1 is an aryl group optionally having one or more substituent(s), R 2 and R 3 are each, independently, a hydrogen atom or an aryl group optionally having one or more substituent(s), and L 1 is a single bond, —O—CO— or —O—CH 2 —; and
said second peptide contains at least one sulfur-containing amino acid residue selected from the group consisting of methionine, cysteine with protected sulfanyl group, and cysteine, and
wherein said method further comprises subjecting said second peptide to hydrogenation in the presence of a metal catalyst and a halogenated acetic acid.

2. The method according to claim 1 , wherein said halogenated acetic acid is at least one member selected from the group consisting of trichloroacetic acid, dichloroacetic acid, monochloroacetic acid, trifluoroacetic acid, difluoroacetic acid, and monofluoroacetic acid.

3. The method according to claim 1 , wherein said hydrogenation is conducted in the presence of trifluoroacetic acid.

4. The method according to claim 1 , wherein said hydrogenation is conducted in the presence of said halogenated acetic acid in an amount of not less than 1 mol per 1 mol of total sulfur atom contained in said sulfur-containing peptide.

5. The method according to claim 1 , wherein said metal catalyst is at least one member selected from the group consisting of a nickel catalyst, a copper catalyst, a ruthenium catalyst, a palladium catalyst, a rhodium catalyst, and a platinum catalyst.

6. A method of producing a sulfur-containing peptide, comprising:
(a) reacting:
(i) a free amino group of an amino acid having a carboxy group protected by a protecting group or a first peptide having the C-terminus protected by a protecting group with
(ii) a free carboxy group of an amino acid having an amino group protected by a protecting group to obtain a second peptide;

(b) deprotecting the protected N-terminus of said second peptide, to obtain a third peptide containing an unprotected amino group;
(c) repeating step (a) and step (b) as necessary; and
(d) deprotecting all of the C-terminus and N-terminus, which are protected by a protecting group, of said third peptide, to obtain said sulfur-containing peptide,
wherein said third peptide contains at least one functional group selected from the group consisting of a carboxy group, an amino group, and a hydroxy group, which is protected by a protecting group represented by formula (I):
R 1 —C(R 2 )(R 3 )-L 1 -  (I)

wherein said R 1 is an aryl group optionally having one or more substituent(s), R 2 and R 3 are each, independently, a hydrogen atom or an aryl group optionally having one or more substituent(s), and L 1 is a single bond, —O—CO— or —O—CH 2 —; and
said third peptide contains at least one sulfur-containing amino acid residue selected from the group consisting of methionine, cysteine with protected sulfanyl group, and cysteine, and
wherein third method further comprises subjecting said third peptide to hydrogenation in the presence of a metal catalyst and a halogenated acetic acid.

7. The method according to claim 6 , wherein said halogenated acetic acid is at least one member selected from the group consisting of trichloroacetic acid, dichloroacetic acid, monochloroacetic acid, trifluoroacetic acid, difluoroacetic acid, and monofluoroacetic acid.

8. The method according to claim 6 , wherein said hydrogenation is conducted in the presence of trifluoroacetic acid.

9. The method according to claim 6 , wherein said hydrogenation is conducted in the presence of said halogenated acetic acid in an amount of not less than 1 mol per 1 mol of total sulfur atom contained in said sulfur-containing peptide.

Assignees

• Ajinomoto Kk

Inventors

• Sajiki Hironao
• Monguchi Yasunari

Classifications

• C07C321/28

  Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07K1/02 Primary

  in solution {(C07K1/003, C07K1/006 take precedence)} · CPC title

• C07K5/0812

  and aromatic or cycloaliphatic · CPC title

• C07K5/06026

  the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala · CPC title

• C07K5/1008

  the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala · CPC title