CN1510025A - Production of monoconfiguration 2-amino-bulyric acid or its derivatives - Google Patents
Production of monoconfiguration 2-amino-bulyric acid or its derivatives Download PDFInfo
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- CN1510025A CN1510025A CNA021581800A CN02158180A CN1510025A CN 1510025 A CN1510025 A CN 1510025A CN A021581800 A CNA021581800 A CN A021581800A CN 02158180 A CN02158180 A CN 02158180A CN 1510025 A CN1510025 A CN 1510025A
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- methionine
- met
- aminobutyric acid
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Abstract
A process for preparing the single-configuration 2-aminobutanoic acid or its derivatives, which can be used as the chirl cell to prepare different chirl compounds including chirl medicines, is disclosed.
Description
Invention field
The invention discloses a kind of method of 2-aminobutyric acid or derivatives thereof of the new single configuration of preparation.2-aminobutyric acid or derivatives thereof can be used to prepare multiple chipal compounds as chirality unit, comprising chiral drug, as Levetiracetam etc.
Background of invention
In recent years, be accompanied by the going deep into of research of life science being carried out molecular level, the effect that the steric configuration of molecule is played in biological phenomena obtains more and more higher attention and research more and more widely.Increasing result of study shows that the compound of three-dimensional arrangement isomer often has complete difference or even opposite biological activity each other.Wherein, contain the compound of chiral centre, more representative and popularity.For example, in synthetic drugs, many results of study show, the medicine that contains chiral centre, the steric configuration of its property of medicine and molecule has confidential relation, and often a kind of steric isomer has drug effect, then drug effect is very little for its mirror image molecule, or does not have drug effect fully or even have an opposite drug effect.Owing to above-mentioned result of study, press for the compound of the single configuration that obtains more and more high-optical-purities.This need directly promote modern vitochemical development.
In organic chemistry method commonly used at present, the approach that obtains the single enantiomer compound mainly contains three kinds:
One,, obtains the enantiomorph of single configuration with the method for racemic modification by optical resolution.This is this method more traditional, that still use always at present, and resulting product purity, cost depend primarily on purity, the cost of chiral separation agent.Generally speaking, use this method cost all higher.
Two,, obtain the enantiomorph of single configuration by the method for asymmetric synthesis.This be receive much attention in the organic chemistry filed in recent years, also be a direction with fastest developing speed, many outstanding chemists wherein occurred and made this technology be able to practical application, very control as Sharpless, according to the open country etc.But because present cost and optical purity factor, this method is not widely used as yet.
Three, by introducing the chirality unit of single configuration, obtain the enantiomorph of single configuration.Chirality unit can be by natural optically active compound preparation, mainly from three kinds of raw materials: amino acid, terpene and carbohydrate and some natural alcohol acids.These raw materials add the development of modern extraction, fermentation technique owing to extensively exist in natural product, thereby cheap, and the optical purity height is the main method of the single configuration of compound of preparation high-optical-purity.
The 2-aminobutyric acid or derivatives thereof of single configuration can be used to prepare multiple chipal compounds as chirality unit, comprising chiral drug, as Levetiracetam etc.In reported method in the past, the 2-aminobutyric acid of single configuration mainly extracts (as: Oikawa, Chem., Zentr., 1,148,1926) from protein.In these methods, all do not mention the method for mentioning among the present invention.
We are surprised to find, and the reaction of the devulcanization of methionine(Met) or derivatives thereof is to have stereoselectively, and promptly the 2-aminobutyric acid or derivatives thereof that obtains after the reaction can keep original steric configuration.Because methionine(Met) particularly L-methionine(Met) is naturally occurring, inexpensive, be easy to get, therefore can prepare corresponding L-2-aminobutyric acid, D-2-aminobutyric acid or derivatives thereof economically by L-methionine(Met), D-methionine(Met) or derivatives thereof according to method provided by the invention.
Goal of the invention
The method that the purpose of this invention is to provide the 2-aminobutyric acid or derivatives thereof of new, an economic single configuration of preparation.
Summary of the invention
The present invention relates to the method for the 2-aminobutyric acid or derivatives thereof of new, an economic single configuration of preparation.
The 2-aminobutyric acid or derivatives thereof of single configuration can be used to prepare multiple chipal compounds as chirality unit, comprising chiral drug, as being that starting raw material can prepare Levetiracetam with the L-2-aminobutyric acid.In reported method in the past, the 2-aminobutyric acid of single configuration mainly extracts (as: Oikawa, Chem., Zentr., 1,148,1926) from protein.
Now, we are surprised to find, the reaction of the devulcanization of methionine(Met) or derivatives thereof be have stereoselective, promptly the 2-aminobutyric acid or derivatives thereof that obtains after the reaction can keep original steric configuration, therefore can prepare corresponding L-2-aminobutyric acid, D-2-aminobutyric acid or derivatives thereof by L-methionine(Met), D-methionine(Met) or derivatives thereof.
Preparation flow is as follows:
With the methionine(Met) or derivatives thereof of L or D configuration, in the presence of sweetening agent, in water, 50～100 ℃ of reactions down.Usually sweetening agent is NaBH
4/ NiCl
2H
2O, Raney nickel W-2 or Raney nickel T-1, preferred Raney nickel T-1.Reaction solution is removed purifying behind the solvent, adopt the method for sedimentation or recrystallization usually, obtain and the corresponding L-2-aminobutyric acid of raw material configuration, D-2-aminobutyric acid or derivatives thereof.Here, derivative typically refer to amino carboxylic acid is protected respectively or simultaneously the protection after derivative.
To the optical purity of product, can be by measuring the specific rotation light value or after deriving, carrying out chirality HPLC analysis and determine.
Preferred sweetening agent Raney nickel T-1, but the method for describing in the reference literature " J.Org.Chem., 26,1625,1961. " preparation.
Method of the present invention has following advantage:
Raw material inexpensive, be easy to get;
2. owing to kept steric configuration in the reaction process, therefore can obtain the product of high-optical-purity.
The following examples are intended to illustrate the present invention, and unrestricted the present invention.
Embodiment
Embodiment 1
In the 5 liter there-necked flasks, add 103 gram Raney nickel T-1,800 ml waters, 11 gram L-methionine(Met), 75 ℃ were reacted 1 hour.Reaction is finished, and filtering Raney nickel T-1 removes water under reduced pressure, gets sky-blue solid 15.6 grams.Add the dissolving of 45 ml waters, the filtering insolubles stirs 900 milliliters of ethanol of adding in filtrate down, separates out white crystals.Filter, drying gets white crystals 5.9 grams, yield: 54%.
mp＞300℃
[α]
20 D＝+21.50°(c＝2.0，5N?HCl)
The proton nmr spectra data are as follows:
1H-NMR (300MHz, D
2O) δ: 0.84 (3H, t, J=7.5Hz ,-CH
3), 1.76 (2H, m ,-CH
2), 3.57 (1H, m ,-CH).
Embodiment 2
According to the method for embodiment 1, be raw material with 10 gram D-methionine(Met), get D-2-aminobutyric acid 5.0 grams.
mp＞300℃
[α]
20 D＝-21.30°(c＝2.0，5N?HCl)
Claims (9)
1. the method for the 2-aminobutyric acid or derivatives thereof of the new single configuration of preparation, this method comprise the methionine(Met) or derivatives thereof and to obtain the 2-aminobutyric acid or derivatives thereof of single configuration through the reaction of devulcanization hydrogenolysis.
2. the method for claim one, wherein the methionine(Met) derivative be amino or carboxylic acid protected respectively or protection simultaneously after the methionine(Met) derivative.
3. the method for claim one, wherein the 2-amino butyric acid derivative be amino or carboxylic acid protected respectively or protection simultaneously after the 2-amino butyric acid derivative.
4. the method for claim one, wherein 2-aminobutyric acid or derivatives thereof is the D configuration.
5. the method for claim one, wherein 2-aminobutyric acid or derivatives thereof is the L configuration.
6. the method for claim one, wherein the methionine(Met) or derivatives thereof is the D configuration.
7. the method for claim one, wherein the methionine(Met) or derivatives thereof is the L configuration.
8. the method for claim one, wherein the reaction of devulcanization hydrogenolysis is for to carry out in the presence of sweetening agent, and sweetening agent is NaBH
4/ NiCl
2H
2O, Raney nickel W-2 or Raney nickel T-1, preferred Raney nickel T-1.
9. the method for claim one, wherein the reaction of devulcanization hydrogenolysis generally is in water, carries out under 50～100 ℃ the condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021581800A CN1510025A (en) | 2002-12-24 | 2002-12-24 | Production of monoconfiguration 2-amino-bulyric acid or its derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021581800A CN1510025A (en) | 2002-12-24 | 2002-12-24 | Production of monoconfiguration 2-amino-bulyric acid or its derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1510025A true CN1510025A (en) | 2004-07-07 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA021581800A Pending CN1510025A (en) | 2002-12-24 | 2002-12-24 | Production of monoconfiguration 2-amino-bulyric acid or its derivatives |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772222A (en) * | 2013-12-30 | 2014-05-07 | 广州远图生物科技有限公司 | Preparation method of improved 2-amunobytyric acid |
-
2002
- 2002-12-24 CN CNA021581800A patent/CN1510025A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103772222A (en) * | 2013-12-30 | 2014-05-07 | 广州远图生物科技有限公司 | Preparation method of improved 2-amunobytyric acid |
| CN103772222B (en) * | 2013-12-30 | 2015-06-24 | 广州远图生物科技有限公司 | Preparation method of improved 2-amunobytyric acid |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |