CN101225427B - Method for improving reaction rate of enzymatic ibuprofen chiral separation - Google Patents
Method for improving reaction rate of enzymatic ibuprofen chiral separation Download PDFInfo
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- CN101225427B CN101225427B CN2007100325200A CN200710032520A CN101225427B CN 101225427 B CN101225427 B CN 101225427B CN 2007100325200 A CN2007100325200 A CN 2007100325200A CN 200710032520 A CN200710032520 A CN 200710032520A CN 101225427 B CN101225427 B CN 101225427B
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- ibuprofen
- enzyme
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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 | 34.140.8 | ?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 | 31.436.3 | ?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; Described nano-carrier immobilized enzyme is the nano-carrier immobilized lipase.
2. method according to claim 1 is characterized in that described nano-carrier immobilized lipase is nano-carrier immobilized candida antarctica lipase A.
3. method according to claim 1 is characterized in that described ionic liquid closes 1-methyl-3-butyl imidazole salt for phosphofluoric acid amine or Tetrafluoroboric acid amine closes 1-methyl 3-butyl imidazole salt.
Priority Applications (1)
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CN2007100325200A CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
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CN2007100325200A CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
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CN101225427A CN101225427A (en) | 2008-07-23 |
CN101225427B true CN101225427B (en) | 2011-07-20 |
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CN2007100325200A Expired - Fee Related CN101225427B (en) | 2007-12-14 | 2007-12-14 | Method for improving reaction rate of enzymatic ibuprofen chiral separation |
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Families Citing this family (1)
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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 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1215085A (en) * | 1998-10-12 | 1999-04-28 | 华东理工大学 | Enzyme method separation process for racemic ketoprofen |
CN1314336A (en) * | 2000-03-16 | 2001-09-26 | 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
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1215085A (en) * | 1998-10-12 | 1999-04-28 | 华东理工大学 | Enzyme method separation process for racemic ketoprofen |
CN1314336A (en) * | 2000-03-16 | 2001-09-26 | 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 |
Non-Patent Citations (2)
Title |
---|
Yu Hongwei, et al..kinetic resolution of ibuprofen catalyzed by candida rugosalipase in ionic liquids.CHIRALITY17 1.2005,17(1),第16-21页. |
Yu Hongwei, et al..kinetic resolution of ibuprofen catalyzed by candida rugosalipase in ionic liquids.CHIRALITY17 1.2005,17(1),第16-21页. * |
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