CN100999749A - Process of preparing 5-fluorouradine ester by enzyme catalyzing - Google Patents
Process of preparing 5-fluorouradine ester by enzyme catalyzing Download PDFInfo
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- CN100999749A CN100999749A CNA2007100262184A CN200710026218A CN100999749A CN 100999749 A CN100999749 A CN 100999749A CN A2007100262184 A CNA2007100262184 A CN A2007100262184A CN 200710026218 A CN200710026218 A CN 200710026218A CN 100999749 A CN100999749 A CN 100999749A
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Abstract
The present invention discloses enzyme catalyzed process of preparing 5-fluoro uridine ester. The process includes reaction of 5-fluoro uridine, reaction medium, C2-C24 enol carboxylate or carboxylic anhydride with 0-6 double bonds and lipase or protease in 50000-800000 U for each gram of 5-fluoro uridine in a reactor at temperature 30-60 deg.c, vibrating speed of 150-250 rpm and normal pressure for 3-12 hr; and subsequent separation to obtain 5-fluoro uridine ester. The lipase is Candida antarctica, Thermomyces lanuginosus, Rhizomucor miehei, Burkholderia cepacia or Pseudomonas sp.; and the reaction medium is organic solvent and/or ionic liquid. The present invention has the advantages of mild reaction condition, environment friendship, controllable reaction process and selectable high temperature region, and easy product separation.
Description
Technical field
The present invention relates to give birth to the non-natural nucleoside medicine of uridine analogue, particularly relate to a kind of method of preparing 5-fluorouradine ester by enzyme catalyzing.
Background technology
The 5-floxuridine is a class non-natural nucleoside, belongs to the uridine analogue, is the antimetabolic antitumour drug, is used for the treatment of the cancer of Digestive tract, reproductive system and lung cancer, skin carcinoma, incidence cancer etc.5-floxuridine ester derivative is one of prodrug of 5-floxuridine, and its hydroxyl by acidylate 5-floxuridine glycosyl part gets.Wherein the structural formula of 5-floxuridine as shown in Figure 1, the structural formula of 5-floxuridine ester as shown in Figure 2, wherein R is saturated or undersaturated aliphatic chain, or fragrant chain.Pharmacology test is the result show, 5-floxuridine ramification of carboxylic esters is more suitable in system or local treating malignant tumor than 5-floxuridine itself, especially for the malignant tumour in reticuloendothelial system and the central nervous system, more remarkable treatment effect.5-floxuridine ramification of carboxylic esters also shows good activity in the treatment noumenal tumour in addition, and therefore, it has caused people's extensive concern as new type antineoplastic medicine.
5-floxuridine ramification of carboxylic esters all adopts chemical method synthetic at present.But because that sugar ring is gone up hydroxyl is numerous, and reactive behavior is similar, and when adopting general chemical process direct esterification, regioselectivity is very low, easily produces a large amount of by products, the product separation difficulty; Be the synthetic product of determining the position acidylate, need encircle specific hydroxyl to sugar and protect and go operation such as protection, many, the complex process of reactions steps; This method adopts basic catalyst simultaneously, easily produces alkali waste, and environment is caused severe contamination.
Summary of the invention
The objective of the invention is to problem at the prior art existence, a kind of method of preparing 5-fluorouradine ester by enzyme catalyzing is provided, this method regioselectivity height, productive rate reaches more than 95%, product structure is easily controlled, can obtain 5-floxuridine 5 '-monoesters or 3 '-monoesters, and product purity height, byproduct of reaction is few.
Purpose of the present invention is achieved through the following technical solutions:
A kind of method of preparing 5-fluorouradine ester by enzyme catalyzing: in reactor, add 5-floxuridine, reaction medium, carboxylic acid enol ester or acid anhydrides, the lipase or the proteolytic enzyme that add 50000～800000U by every gram 5-floxuridine, in temperature is after 30～60 ℃, hunting speed are to react 3～12 hours under 150～250rpm, the condition of normal pressure, to obtain 5-floxuridine ester through separation;
Described lipase derives from Candida antarctica, Thermomyces lanuginosus, Rhizomucormiehei, Burkholderia acepacia or Pseudomonas sp.; Described proteolytic enzyme derives from Bacillus sp.;
The carbonatoms of acyl group is C2～C24 in described carboxylic acid enol ester or the acid anhydrides, contains 0～6 two key; The mol ratio of carboxylic acid enol ester or acid anhydrides and 5-floxuridine is 9: 1～100: 1;
Described reaction medium is organic solvent and/or ionic liquid; Its consumption is to add 0.1～1L by every gram 5-floxuridine.
Preferred version is as follows: described organic solvent is a kind of in aliphatic saturated hydrocarbon, unsaturated aliphatic hydrocarbon, aromatic hydrocarbons, ester class, fatty ether, aryl oxide, alcohols, the nitrogenous compound solvent or more than one.
In the described organic solvent, hydrophobic organic solvent accounts for 5～30% volumes.
The negatively charged ion of ionic liquid is tetrafluoroborate ion, hexafluorophosphoricacid acid ions or nitrate ion, and positively charged ion is 1-alkyl-3-Methylimidazole ion, 1-alkyl-3-alkoxyl group imidazol ion or 1-alkyl-3-picoline ion.
Separate 5-floxuridine ester and can adopt the prior art method in common, the following method that also can adopt the inventor to invent: after reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, with ethanol or re-crystallizing in ethyl acetate or process silica gel column chromatogram separating purification, promptly get 5-floxuridine ester after the concentrated solution vacuum-drying.
The principle of the invention: with carboxylic acid enol ester or acid anhydrides is acry radical donor, utilizes enzyme catalysis 5-floxuridine to carry out acylation reaction, the synthetic 5-floxuridine ester that obtains;
The present invention has following advantage compared with prior art:
(1) adopting efficiently, the biological catalyst enzyme comes catalysis 5-floxuridine ester synthetic, enzymic catalytic reaction has high selectivity, product structure is easily controlled, can obtain as required 5-floxuridine 5 '-monoesters or 3 '-monoesters, purpose product productive rate height, by product is few, therefore overcome traditional chemical method selectivity low, easily generate shortcomings such as by product, purpose product purity and productive rate are low;
(2) the present invention need not protect with going by radical protection, and reaction process is simple and easy to control, and product is easily separated;
(3) the present invention is to be that 30～60 ℃, hunting speed are the following preparing 5-fluorouradine ester by enzyme catalyzing of 150～250rpm, condition of normal pressure in temperature, reaction conditions gentleness, environmental friendliness.
Fig. 1 is the structural formula of 5-floxuridine.
Fig. 2 is the structural formula of 5-floxuridine ester.
Fig. 3 is the high-efficient liquid phase chromatogram behind the embodiment 1 reaction 3h.
Fig. 4 is the mass spectrum of embodiment 1.
Fig. 5 is the infrared spectrogram of embodiment 1.
Fig. 6 is the nucleus magnetic resonance figure of embodiment 1.
Embodiment
For better understanding the present invention, below in conjunction with embodiment the present invention is done detailed description further, but the scope of protection of present invention is not limited to the scope that embodiment represents.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 2.10g (1.84 * 10
-2Mol) reaction solution of vinyl butyrate, 0.1L acetonitrile joins in the tool plug triangular flask, then add 50,000U derive from Candidaantarctica lipase (10,000U/g), place vibration in 40 ℃, the constant temperature water bath vibrator of 150rpm under the normal pressure, behind the reaction 3h, reaction mixture is dezymotized after filtration, and vacuum-evaporation concentrates, after the concentrated solution vacuum-drying, with the ethyl alcohol recrystallization separation and purification, promptly get product 0.596g, yield is 97.0%.Adopt reversed-phased high performace liquid chromatographic, under following testing conditions: the detection wavelength is 269nm; Chromatographic column: 4.6 * 250mm5 μ mZorbax XDB-C18 analysis mode chromatographic column; Moving phase: 40% methyl alcohol-60% aqueous solution (v/v); Flow velocity: 0.6mL/min column temperature: 25 ℃; Sample size: 20 μ L; Carry out check and analysis; This conversion zone selectivity of analysis revealed is 99.9%, and production concentration is higher than 99%.The mass spectrum result confirms that this product only is 5-floxuridine monoesters product; The infrared spectra detected result shows that this enzymatic reaction is an acylation reaction, again through the further analysis revealed acidylate of nucleus magnetic resonance occur in 5 of 5-floxuridine '-position, that is the product that generates be 5-floxuridine 5 '-butyric ester.The product analysis of following examples is also so routine, repeats no more.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 3.41g (2.05 * 10
-2Mol) reaction solution of sad vinyl acetate, 0.5L acetonitrile joins in the tool plug triangular flask, then add 70,000U derive from Candidaantarctica lipase (10,000U/g), place vibration in 40 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 5h, reaction mixture is dezymotized after filtration, and vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the re-crystallizing in ethyl acetate separation and purification, promptly get product 0.846g, yield is 97.2%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, the result show the product that makes be 5-floxuridine 5 '-laurate, the conversion zone selectivity is 99.9%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 20.84g (8.2 * 10
-2Mol) reaction solution of myristic acid vinyl acetate, 0.5L20% (v/v) tetrahydrofuran (THF)-acetone (1: 4) mixed solvent joins in the tool plug triangular flask, then add 70,000U derives from the lipase (10 of Candida antarctica, 000U/g), place vibration in 55 ℃, the constant temperature water bath vibrator of 250rpm under the normal pressure, behind the reaction 6h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, concentrated solution vacuum-drying is after silica gel column chromatogram separating purification, promptly get product 1.04g, yield is 95.7%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-myristate, the conversion zone selectivity is 99.9%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 4.59g (2.05 * 10
-2Mol) reaction solution of vinyl laurate, 0.5L15% (v/v) tetrahydrofuran (THF)-acetone (15: 85) mixed solvent joins in the tool plug triangular flask, then add 100,000U derives from the lipase (50 of Thermomyces lanuginosus, 000U/g), place vibration in 45 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 4h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the ethyl alcohol recrystallization separation and purification, promptly get product 0.901g, yield is 97.5%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-laurate, the conversion zone selectivity is 99.9%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 5.78g (2.05 * 10
-2Mol) palmitinic acid vinyl acetate, the reaction solution of 0.1L8% (v/v) ionic liquid 1-butyl-3-Methylimidazole hexafluorophosphate and tetrahydrofuran (THF) (8: 92) mixed solvent is added in the tool plug triangular flask, then add 100,000U derives from the lipase (50 of Thermomyceslanuginosus, 000U/g), place 40 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 6h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the re-crystallizing in ethyl acetate separation and purification, promptly get product 0.964g, yield is 96.5%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-cetylate, the conversion zone selectivity is 99.0%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 142g (2.05 * 10
-1Mol) 4,7,10,13,16,19-docosene vinyl acetate, the reaction solution of 0.50L10% (v/v) ionic liquid 1-octyl group-3-methyl imidazolium tetrafluoroborate and the trimethyl carbinol (1: 9) mixed solvent joins in the tool plug triangular flask, then add 200,000U derive from Thermomyces lanuginosus lipase (50,000U/g), place 50 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 8h, reaction mixture is dezymotized after filtration, and vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the ethyl alcohol recrystallization separation and purification, promptly get product 0.972g, yield is 95.6%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-the docosene acid esters, the conversion zone selectivity is 99.0%, production concentration reaches more than 98%.
Embodiment 7
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 14.83g (1.025 * 10
-2Mol) reaction solution of vinyl benzoate, 0.10L ionic liquid 1-butyl-3-Methylimidazole hexafluorophosphate joins in the tool plug triangular flask, then add 150,000U derives from the lipase (20 of Rhizomucor miehei, 000U/g), place vibration in 55 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 8h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying through silica gel column chromatogram separating purification, promptly get product 0.657g, yield is 95.1%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-benzoic ether, the conversion zone selectivity is 99.0%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 24.0g (1.23 * 10
-2Mol) reaction solution of certain herbaceous plants with big flowers vinyl acetate, 0.15L20% (v/v) ionic liquid 1-ethyl-3-methyl imidazolium tetrafluoroborate and pyridine (1: 4) mixed solvent joins in the tool plug triangular flask, then add 250,000U derives from the lipase (20 of Rhizomucor miehei, 000U/g), place vibration in 40 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 6h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying through silica gel column chromatogram separating purification, promptly get product 0.682g, yield is 97.5%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-the certain herbaceous plants with big flowers acid esters, the conversion zone selectivity is 99.5%, production concentration reaches more than 99%.
Embodiment 9
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 636g (3.75 * 10
-2Mol) reaction solution of stearic acid vinyl ester, 0.5L5% (v/v) ionic liquid 1-butyl-3-Methylimidazole hexafluorophosphate and acetone (5: 95) mixed solvent joins in the tool plug triangular flask, then add 100,000U derives from the lipase (50 of Thermomyceslanuginosus, 000U/g), place vibration in 55 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 6h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the ethyl alcohol recrystallization separation and purification, promptly get product 1.02g, yield is 97.0%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-stearate, the conversion zone selectivity is 99.0%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 14.78g (3.75 * 10
-2Mol) reaction solution of tetracosa carbon vinyl acetate, 0.5L25% (v/v) isopropyl ether and pyridine (1: 3) mixed solvent joins in the tool plug triangular flask, then add 100,000U derives from the lipase (30 of Pseudomonas sp., 000U/g), place vibration in 55 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 12h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the re-crystallizing in ethyl acetate separation and purification, promptly get product 1.03g, yield is 96.4%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 3 '-the tetracosa carbon acid esters, the conversion zone selectivity is 99.0%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 8.48g (3.75 * 10
-2Mol) benzoyl oxide, 0.5L30% (v/v) pyridine He the reaction solution of diox (3: 7) mixed solvent join in the tool plug triangular flask, then add 200,000U derive from Pseudomonas sp. lipase (30,000U/g), place vibration in 55 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 8h, reaction mixture is dezymotized after filtration, and vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the ethyl alcohol recrystallization separation and purification, promptly get product 0.703g, yield is 97.2%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 3 '-benzoic ether, the conversion zone selectivity is 99.9%, production concentration reaches more than 99%.
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 56.4g (2.05 * 10
-1Mol) oleic acid vinyl acetate, 0.1L20% (v/v) acetonitrile He the reaction solution of diox (1: 4) mixed solvent join in the tool plug triangular flask, then add 20,000U derives from the lipase (10 of Candida antarctica, 000U/g), place vibration in 45 ℃, the constant temperature water bath vibrator of 250rpm under the normal pressure, behind the reaction 8h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying through silica gel column chromatogram separating purification, promptly get product 0.986g, yield is 96.2%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-oleic acid ester, the conversion zone selectivity is 99.9%, production concentration reaches more than 99%.
Embodiment 13
To contain 0.53g (2.05 * 10
-3Mol) 5-floxuridine, 10.13g (2.05 * 10
-2Mol) reaction solution of lauric anhydride, 0.5L25% (v/v) octane-iso-dimethyl formamide (1: 3) mixed solvent joins in the tool plug triangular flask, then add 100,000U derives from the lipase (30 of Burkholderia cepacia, 000U/g), place vibration in 45 ℃, the constant temperature water bath vibrator of 200rpm under the normal pressure, behind the reaction 8h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with the re-crystallizing in ethyl acetate separation and purification, promptly get product 0.854g, yield is 97.0%; Through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 3 '-laurate, the conversion zone selectivity is 99.5%, production concentration reaches more than 99%.
To contain 0.5g (2.05 * 10
-3Mol) 5-floxuridine, 111.9g (2.05 * 10
-1Mol) oil anhydride, the reaction solution of 0.5L20% (v/v) trimethyl carbinol-acetone (1: 4) mixed solvent joins in the tool plug triangular flask, then add 150,000U derives from the proteolytic enzyme (2 of Bacillus sp., 400U/g), place 45 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 12h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying through silica gel column chromatogram separating purification, promptly get product 0.952g, yield is 97.1%, through nucleus magnetic resonance, mass spectrum, infrared spectra and high-efficient liquid phase chromatogram technique analysis, analytical procedure is with embodiment 1, show the product that makes be 5-floxuridine 5 '-oleic acid ester, the conversion zone selectivity is 99.5%, production concentration reaches more than 99%.
Claims (5)
1, a kind of method of preparing 5-fluorouradine ester by enzyme catalyzing, it is characterized in that: in reactor, add 5-floxuridine, reaction medium, carboxylic acid enol ester or acid anhydrides, the lipase or the proteolytic enzyme that add 50000～800000U by every gram 5-floxuridine, in temperature is after 30～60 ℃, hunting speed are to react 3～12 hours under 150～250rpm, the condition of normal pressure, to obtain 5-floxuridine ester through separation;
Described lipase derives from Candida antarctica, Thermomyces lanuginosus, Rhizomucormiehei, Burkholderia acepacia or Pseudomonas sp.; Described proteolytic enzyme derives from Bacillus sp.;
The carbonatoms of acyl group is C2～C24 in described carboxylic acid enol ester or the acid anhydrides, contains 0～6 two key; The mol ratio of carboxylic acid enol ester or acid anhydrides and 5-floxuridine is 9: 1～100: 1;
Described reaction medium is organic solvent and/or ionic liquid; Its consumption is to add 0.1～1L by every gram 5-floxuridine.
2, method according to claim 1 is characterized in that described organic solvent is one or more in aliphatic saturated hydrocarbon, unsaturated aliphatic hydrocarbon, aromatic hydrocarbons, ester class, fatty ether, aryl oxide, alcohols, the nitrogenous compound solvent.
3, method according to claim 2 is characterized in that in the described organic solvent, hydrophobic organic solvent accounts for 5～30% volumes.
4, method according to claim 1, it is characterized in that ionic liquid comprises negatively charged ion liquid and cationic liquid, described negatively charged ion is tetrafluoroborate ion, hexafluorophosphoricacid acid ions or nitrate ion, and positively charged ion is 1-alkyl-3-Methylimidazole ion, 1-alkyl-3-alkoxyl group imidazol ion or 1-alkyl-3-picoline ion.
5, method according to claim 1, it is characterized in that separating after the method that obtains 5-floxuridine ester is meant that reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, after the concentrated solution vacuum-drying with methyl alcohol, ethanol or re-crystallizing in ethyl acetate, perhaps pass through silica gel column chromatogram separating purification, promptly get 5-floxuridine ester.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492743A (en) * | 2011-11-28 | 2012-06-13 | 浙江工业大学 | Method for preparing medium-chain triglyceride from ionic liquid |
| CN104630302A (en) * | 2013-11-06 | 2015-05-20 | 江苏省农业科学院 | Enzyme process acylation method of strawberry anthocyanin |
| CN104630315A (en) * | 2013-11-06 | 2015-05-20 | 江苏省农业科学院 | Reduced pressure enzyme process acylation method of black rice pigment |
| CN107384991A (en) * | 2016-05-17 | 2017-11-24 | 浙江工业大学 | A kind of method of 5 '-O- ethene adipyl uridines of lipase-catalyzed online synthesis |
-
2007
- 2007-01-05 CN CNA2007100262184A patent/CN100999749A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492743A (en) * | 2011-11-28 | 2012-06-13 | 浙江工业大学 | Method for preparing medium-chain triglyceride from ionic liquid |
| CN102492743B (en) * | 2011-11-28 | 2013-11-13 | 浙江工业大学 | Method for preparing medium-chain triglyceride from ionic liquid |
| CN104630302A (en) * | 2013-11-06 | 2015-05-20 | 江苏省农业科学院 | Enzyme process acylation method of strawberry anthocyanin |
| CN104630315A (en) * | 2013-11-06 | 2015-05-20 | 江苏省农业科学院 | Reduced pressure enzyme process acylation method of black rice pigment |
| CN104630315B (en) * | 2013-11-06 | 2018-08-14 | 江苏省农业科学院 | A kind of decompression enzyme process acylation method of black rice pigments |
| CN107384991A (en) * | 2016-05-17 | 2017-11-24 | 浙江工业大学 | A kind of method of 5 '-O- ethene adipyl uridines of lipase-catalyzed online synthesis |
| CN107384991B (en) * | 2016-05-17 | 2020-11-13 | 浙江工业大学 | Method for synthesizing 5' -O-ethylene adipamide uridine on line by lipase catalysis |
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