Branched chain-containing aromatic compound

Patent metadata

Field	Value
Publication number	US-9499579-B2
Application number	US-201314013590-A
Country	US
Kind code	B2
Filing date	Aug 29, 2013
Priority date	Aug 30, 2010
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

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.

First claim

The invention claimed is:

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.

Assignees

• Ajinomoto Kk

Inventors

• Takahashi Daisuke

Classifications

• C07C43/225 Primary

  containing halogen · CPC title

• C07C217/58

  with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain · CPC title

• C07K5/1021

  with the first amino acid being acidic · CPC title

• C07C43/23 Primary

  containing hydroxy or O-metal groups · CPC title

• C07C2603/18

  Fluorenes; Hydrogenated fluorenes · CPC title