IP Library Granted Patent US 9,499,579
Granted Patent B2
US 9,499,579 · App. 14/013,590 · Granted Nov 22, 2016

Branched chain-containing aromatic compound

Inventor: Daisuke Takahashi (Yokkaichi, JP)
Assignee: AJINOMOTO CO., INC.
C07K1/066C07C43/225C07C43/23C07C235/42C07K1/062C07K5/0819C07K5/1021C07K7/06C07C2103/18
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Quick Facts
Patent No.
US 9,499,579
App. No.
14/013,590
Granted
Nov 22, 2016
Kind
B2
Abstract

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step.

Claims (35)

1. A method of producing a peptide comprising:

(1) removing an N-terminal protecting group from (i) an N-protected C-protected amino acid or (ii) a first N-protected C-protected peptide, wherein said N-protected C-protected amino acid and said first N-protected C-protected peptide have a C-terminus protected with an anchor which is a protecting group derived from a branched chain-containing aromatic compound, to obtain a C-protected amino acid or C-protected peptide;

(2) condensing an N-protected amino acid or N-protected peptide with the N-terminus of said C-protected amino acid or C-protected peptide to obtain a second N-protected C-protected peptide; and

(3) removing the N-terminal protecting group and the C-terminal anchor from said second N-protected C-protected peptide, to obtain said peptide,

wherein said branched chain-containing aromatic compound is represented by formula (I):

wherein

each Q is independently a single bond, or —O—, —S—, —C(═O)O—, —C(═O)NH— or —NH—;

each R a is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of branched chains in each R a is not less than 3 and a total carbon number in each R a is not less than 14 and not more than 300;

k is an integer of 1 to 4;

R 1 is a hydrogen atom or, when Z is a group represented by formula (a), it optionally forms a single bond together with R 2 to form a fluorene ring together with ring B;

ring A optionally further has, in addition to R 1 , (QR a ) k , and C(X)(Y)Z, one or more substituents selected from the group consisting of a halogen atom, a C 1-6 alkyl group optionally substituted by one or more halogen atoms, and a C 1-6 alkoxy group optionally substituted by one or more halogen atoms;

X is a hydrogen atom or a phenyl group;

Y is a hydroxyl group, an —NHR group (wherein R is a hydrogen atom, an alkyl group, or an aralkyl group), or a halogen atom; and

Z is a hydrogen atom or a group represented by formula (a):

wherein

* indicates the bonding position;

m is an integer of 0 to 4;

each Q is as defined above;

each R b is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of the branched chain in each R b is not less than 3 and a total carbon number in each R b is not less than 14 and not more than 300;

R 2 is a hydrogen atom, or optionally forms a single bond together with R 1 to form a fluorene ring together with ring A; and

ring B optionally further has, in addition to (QR b ) m and R 2 , one or more substituents selected from the group consisting of a halogen atom, a C 1-6 alkyl group optionally substituted by one or more halogen atoms, and a C 1-6 alkoxy group optionally substituted by one or more halogen atoms;

wherein said organic group having at least one aliphatic hydrocarbon group having one or more branched chains, a total number of the branched chain of not less than 3 and a total carbon number of not less than 14 and not more than 300 for each R a and R b is a group having 3 or more of the same or different divalent groups represented by formula (b):

wherein

* indicates the bonding position with the adjacent atom;

R 3 and R 4 are each independently a hydrogen atom or a C 1-4 alkyl group;

X 1 is a single bond, a C 1-4 alkylene group, or an oxygen atom,

provided that R 3 and R 4 are not hydrogen atoms at the same time.

2. A method according to claim 1 , further comprising one or more repetitions of steps (4)-(6):

(4) removing the N-terminal protecting group of an obtained N-protected C-protected peptide to obtain a C-protected peptide;

(5) condensing an N-protected amino acid or N-protected peptide with the N-terminus of said obtained C-protected peptide to give another N-protected C-protected peptide; and

(6) adding water to the reaction system after step (5), and separating an impurity by extraction into an aqueous layer.

3. A method according to claim 1 , further comprising one or more repetitions of steps (4)-(6′):

(4) removing the N-terminal protecting group of an obtained N-protected C-protected peptide to obtain a C-protected peptide;

(5) condensing an N-protected amino acid or N-protected peptide with the N-terminus of said obtained C-protected peptide to give another N-protected C-protected peptide; and

(6′) adding a hydrophilic organic solvent to the reaction system after step (5), and separating an impurity by extraction into a hydrophilic organic solvent layer.

Priority Claims (1)
JP 2010-192961 · Aug 30, 2010 · national
Continuity (3)
Division 13220841 · Aug 30, 2011
Provisional Application 61378170 · Aug 30, 2010
Related Publication 20140005359A1 · Jan 2, 2014