CN101225427A - Method for improving reaction rate of enzymatic ibuprofen chiral separation - Google Patents
Method for improving reaction rate of enzymatic ibuprofen chiral separation Download PDFInfo
- Publication number
- CN101225427A CN101225427A CNA2007100325200A CN200710032520A CN101225427A CN 101225427 A CN101225427 A CN 101225427A CN A2007100325200 A CNA2007100325200 A CN A2007100325200A CN 200710032520 A CN200710032520 A CN 200710032520A CN 101225427 A CN101225427 A CN 101225427A
- Authority
- CN
- China
- Prior art keywords
- ibuprofen
- enzyme
- ion liquid
- chiral separation
- carrier immobilized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
The invention discloses a method of increasing the ibuprofen chiral split reaction speed catalyzed by enzyme in ion liquid, which is characterized in that: nanophase carrier immobilized enzyme is dispersed in the ion liquid with ibuprofen and 1-propanol, and the solution is stirred to process reaction for 24 to 48 hours at 25 to 35 degree centigrade; wherein, the molar ratio of ibuprofen and 1-propanol is 1 to 6 : 20, and the weight bulk ratio of the ibuprofen and the ion liquid is 1mg : 2 to 4ml, and the weight bulk ratio of the nanophase carrier immobilized enzyme and the ion liquid is 1g : 4 to 10ml. The method of increasing the ibuprofen chiral split reaction speed catalyzed by enzyme in ion liquid has the advantages of easy method and operation, mass production, being green chemical for enzyme and the ion liquid and being without environment pollution for the reaction of preparing chiral ibuprofen.
Description
Technical field
The present invention relates to a kind of method that improves enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction in the ionic liquid.
Background technology
Ibuprofen BP/EP (ibuprofen, ibuprofen) is the anti-inflammation and analgesic drugs that clinical security commonly used is good, price is low, and S (+)-Ibuprofen BP/EP activity is 160 times of R (-) configuration.Chemical method synthetic Ibuprofen BP/EP is a racemic modification, and fractionation is the main method that obtains optical purity S (+) isomer.Chemistry splits with expensive chiral reagent, and split process is numerous and diverse, is difficult to obtain satisfied yield.It is catalyzer that biological process splits with enzyme, and reaction is selected to split Ibuprofen BP/EP in organic medium, has that the property of choosing is good, the productive rate advantages of higher, but uses the organic medium high volatility always, and environmental pollution is heavier.Ionic liquid is to be made of organic cation and inorganic or organic anion, at the salt that room temperature is in a liquid state, does not have tangible vapour pressure, to thermally-stabilised and have high polarity, is a kind of emerging green reagent.
Summary of the invention
The object of the present invention is to provide a kind of method that improves enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction in the ionic liquid.
The method of enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction in the raising ionic liquid of the present invention was that the nano-carrier immobilized enzyme is dispersed in the ionic liquid that contains Ibuprofen BP/EP and 1-propyl alcohol, 25～35 ℃ of following stirring reactions 24～48 hours; Wherein, the mol ratio of Ibuprofen BP/EP and 1-propyl alcohol is 1～6: 20, Ibuprofen BP/EP: ion liquid mass volume ratio is 1mg: 2～4ml, the nano-carrier immobilized enzyme: ion liquid mass volume ratio is 1g: 4～10ml.
Described nano-carrier immobilized enzyme is antarctic candidia lipase A.
Described ionic liquid closes 1-methyl 3-butyl imidazole salt ([BMIM] [PF for the phosphofluoric acid acid amide
6]) or Tetrafluoroboric acid amine close 1-methyl 3-butyl imidazole salt ([BMIM] [BF
4]).
The present invention compared with prior art has following advantage:
(1) enzyme and ionic liquid are green chemical, and the reaction pair environment of preparation chirality Ibuprofen BP/EP does not pollute.
(2) method is easy to operation, can be mass-produced.
Embodiment
Embodiment 1
5.0g nano-carrier immobilized enzyme antarctic candidia lipase A and 1g lipase are dispersed in [BMIM] [PF that 20ml contains 0.05mM Ibuprofen BP/EP and 0.5mM 1-propyl alcohol respectively
6] in, 35 ℃ of following stirring reactions 24 hours.Measure the content of S (+)-Ibuprofen BP/EP, it is as shown in table 1 to calculate the chiral separation speed of reaction.
Table 1.
| The kind of enzyme | C(％) | ee s(％) | E |
| The lipase immobilization enzyme | 34.1 40.8 | 36.3 45.2 | 8.09 7.44 |
Table 1 explanation, the nano-carrier immobilized enzyme can improve enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction (C) and chirality yield ee in the ionic liquid
s).
Embodiment 2
5.0g nano-carrier immobilized enzyme antarctic candidia lipase A and 1g lipase are dispersed in [BMIM] [BF that 40ml contains 0.05mM Ibuprofen BP/EP and 0.30mM 1-propyl alcohol respectively
4] in, 30 ℃ of following stirring reactions 36 hours.Measure the content of S (+)-Ibuprofen BP/EP, it is as shown in table 2 to calculate the chiral separation speed of reaction.
Table 2
| The kind of enzyme | C(％) | ee s(％) | E |
| The lipase immobilization enzyme | 31.4 36.3 | 29.1 29.8 | 5.93 4.33 |
Table 2 explanation, the nano-carrier immobilized enzyme can improve enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction (C) and chirality yield (ee in the ionic liquid
s).
Embodiment 3
4.0g nano-carrier immobilized enzyme antarctic candidia lipase A and 1g lipase are dispersed in [BMIM] [PF that 40ml contains 0.05mM Ibuprofen BP/EP and 1.0mM 1-propyl alcohol respectively
6] in, 25 ℃ of following stirring reactions 48 hours.Measure the content of S (+)-Ibuprofen BP/EP, it is as shown in table 3 to calculate the chiral separation speed of reaction.
Table 3.
| The kind of enzyme | C(％) | ee s(％) | E |
| The lipase immobilization enzyme | 34.1 42.5 | 36.3 42.4 | 8.09 5.53 |
Table 3 explanation, the nano-carrier immobilized enzyme can improve enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction (C) and chirality yield (ee in the ionic liquid
s).
Claims (3)
1. method that improves enzyme catalysis Ibuprofen BP/EP chiral separation speed of reaction in the ionic liquid is characterized in that: the nano-carrier immobilized enzyme is dispersed in the ionic liquid that contains Ibuprofen BP/EP and 1-propyl alcohol, 25～35 ℃ of following stirring reactions 24～48 hours; Wherein, Ibuprofen BP/EP: the mol ratio of 1-propyl alcohol is 1～6: 20, Ibuprofen BP/EP: ion liquid mass volume ratio is 1mg: 2～4ml, the nano-carrier immobilized enzyme: ion liquid mass volume ratio is 1g: 4～10ml.
2. method according to claim 1 is characterized in that described nano-carrier immobilized enzyme is antarctic candidia lipase A.
3. method according to claim 1 is characterized in that described ionic liquid closes 1-methyl-3-butyl imidazole salt for the phosphofluoric acid acid amide or Tetrafluoroboric acid amine closes 1-methyl-3-butyl imidazole salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100325200A CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100325200A CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101225427A true CN101225427A (en) | 2008-07-23 |
| CN101225427B CN101225427B (en) | 2011-07-20 |
Family
ID=39857632
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100325200A Expired - Fee Related CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101225427B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113088553A (en) * | 2021-03-30 | 2021-07-09 | 东华理工大学 | Method for preparing S-ibuprofen by enzymatic resolution-chemical racemization tandem |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1065917C (en) * | 1998-10-12 | 2001-05-16 | 华东理工大学 | Enzyme method separation process for racemic ketoprofen |
| CN1102137C (en) * | 2000-03-16 | 2003-02-26 | 武汉大学 | Method for splitting ibuprofen by two-component chiral reagent |
| KR100433633B1 (en) * | 2002-04-18 | 2004-05-31 | 학교법인 포항공과대학교 | Method of optical resolution by enzyme using solvent-free two-phase system |
-
2007
- 2007-12-14 CN CN2007100325200A patent/CN101225427B/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113088553A (en) * | 2021-03-30 | 2021-07-09 | 东华理工大学 | Method for preparing S-ibuprofen by enzymatic resolution-chemical racemization tandem |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101225427B (en) | 2011-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cheng et al. | Recent advances in metal-catalysed asymmetric sequential double hydrofunctionalization of alkynes | |
| Rios et al. | Strategies of covalent immobilization of a recombinant Candida antarctica lipase B on pore-expanded SBA-15 and its application in the kinetic resolution of (R, S)-Phenylethyl acetate | |
| Lou et al. | Efficient enantioselective hydrolysis of D, L-phenylglycine methyl ester catalyzed by immobilized Candida antarctica lipase B in ionic liquid containing systems | |
| CN108546720B (en) | Method for preparing (S) -2-phenylbutyric acid through stereoselective enzymatic hydrolysis | |
| CN101818178A (en) | Method for preparing L-2-aminobutyric acid by enzyme method | |
| CN104894148A (en) | Omega-aminotransferase mutant gene and application thereof | |
| Jost et al. | Variants of the acyltransferase from Mycobacterium smegmatis enable enantioselective acyl transfer in water | |
| Boeckman Jr et al. | direct enantioselective organocatalytic hydroxymethylation of aldehydes catalyzed by α, α-diphenylprolinol trimethylsilyl ether | |
| Shimomura et al. | Lipase-mediated dynamic kinetic resolution (DKR) of secondary alcohols in the presence of zeolite using an ionic liquid solvent system | |
| CN102277392A (en) | Method for preparing chemical enzyme of (R)-1-(1-naphthyl) ethylamine by resolution | |
| CN105483105A (en) | Penicillin G acylase mutant | |
| CN111662898A (en) | New lipase immobilization technology and method for applying same to enantiomer resolution | |
| CN104276956B (en) | A kind of preparation method of S-1-tetrahydro naphthylamine | |
| CN101225427B (en) | Method for improving reaction rate of enzymatic ibuprofen chiral separation | |
| CN109777845A (en) | A kind of preparation method of C4H9NO2 | |
| Williams et al. | Highly efficient production of optically active (R)-tetrahydrothiophene-3-ol in batch and continuous flow by using immobilized ketoreductase | |
| Oláh et al. | Lipase B from Candida antarctica immobilized on epoxy-functionalized hollow silica microspheres: efficient biocatalysts for enantiomer selective acylation of alcohols and amines | |
| CN101573326B (en) | Process for production of betaine | |
| CN102174632A (en) | Bio-catalytic deracemization preparation method of non-natural L-amino acid | |
| US20110039314A1 (en) | Composition for Catalytic Amide Production and Uses Thereof | |
| Yildirim et al. | Optimization of immobilization conditions of Mucor miehei lipase onto Florisil via polysuccinimide spacer arm using response surface methodology and application of immobilized lipase in asymmetric acylation of 2-amino-1-phenylethanols | |
| Su et al. | Functional expression of Serratia marcescens H30 lipase in Escherichia coli for efficient kinetic resolution of racemic alcohols in organic solvents | |
| Bustos-Jaimes et al. | Immobilization and enantioselectivity of Bacillus pumilus lipase in ionic liquids | |
| CN114214375B (en) | Process for the preparation of (R) -3- (4-halo-1H-pyrazol-1-yl) -3-cyclopentylpropionate | |
| CN114940983A (en) | Eutectic solvent based on polyalcohol hydrogen bond donor and method for improving catalytic activity of omega-transaminase by using eutectic solvent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110720 Termination date: 20131214 |