CN1661030A - Method of enzyme catalysis for preparing cytosine ester arabinoside - Google Patents
Method of enzyme catalysis for preparing cytosine ester arabinoside Download PDFInfo
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- CN1661030A CN1661030A CN 200410077504 CN200410077504A CN1661030A CN 1661030 A CN1661030 A CN 1661030A CN 200410077504 CN200410077504 CN 200410077504 CN 200410077504 A CN200410077504 A CN 200410077504A CN 1661030 A CN1661030 A CN 1661030A
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- arabinoside
- ester
- cytosine
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- enzyme catalysis
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Abstract
A process for preparing cytosine arabinoside ester by enzyme catalysis in non-water medium features that the carboxylate or carboxylic anhydride is used as the acyl donator and the cytosine arabinoside takes part in acylating reaction in non-water medium under catalysis of enzyme to obtain target product.
Description
Technical field
The invention belongs to biocatalysis and biosynthesizing, biological medicine and material field, relate to a kind of in non-aqueous media the method for enzyme catalysis for preparing cytosine ester arabinoside.
Background technology
Cytosine arabinoside is a class non-natural nucleoside, belongs to the deoxycytidine analogue, has very high anti-leukocythemia liveness, is to be used for the treatment of acute myelogenous leukemia one of the most effective chemotherapeutics clinically.The cytosine arabinoside ester derivative is one of prodrug of cytosine arabinoside, and its hydroxyl by acidylate cytosine arabinoside glycosyl part gets.Pharmacology test is the result show, the cytosine arabinoside ramification of carboxylic esters is more suitable in system or local treating malignant tumor than cytosine arabinoside itself, especially for the malignant tumour in reticuloendothelial system and the central nervous system, more remarkable treatment effect.The cytosine arabinoside 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.
The cytosine arabinoside ramification of carboxylic esters all adopts chemical method synthetic at present.Its subject matter is: it is numerous that sugar ring is gone up hydroxyl, 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 acylate of determining the position, need encircle specific hydroxyl to sugar and protect and go operation such as protection, many, the complex process of reactions steps; Adopt basic catalyst, easily produce alkali waste, environment is caused severe contamination.
Summary of the invention
The objective of the invention is to problem at the prior art processes existence, the method of enzyme catalysis for preparing cytosine ester arabinoside in a kind of non-aqueous media is provided, its selectivity height, product structure is easily controlled, byproduct of reaction is few, product Cytarbine Ocfostate purity height, the selectivity of traditional chemical method is low to cause substrate utilization ratio low thereby overcome, the shortcoming that product purity is low;
The method of enzyme catalysis for preparing cytosine ester arabinoside is to adopt non-aqueous media in the non-aqueous media of the present invention, is acry radical donor with carboxylicesters or acid anhydrides, utilizes the enzyme catalysis cytosine arabinoside to carry out acylation reaction, the synthetic Cytarbine Ocfostate that obtains.
Method of the present invention comprises the steps: in more detail
(1) in reactor, adds cytosine arabinoside, non-aqueous media, carboxylicesters or acid anhydrides successively;
(2) being that the ratio of 100～4000U/ gram cytosine arabinoside adds enzyme in enzyme dosage, is that 25～60 ℃, hunting speed are 100～250rpm/min, reaction 1～48 hour in temperature, separates obtaining Cytarbine Ocfostate.
Described non-aqueous media comprises that organic solvent system or ionic liquid content are the organic solvent and the mixed system of ionic liquid of 0～40% quality, and consumption is 0.5～10L/ gram cytosine arabinoside; The mol ratio of described carboxylicesters or acid anhydrides and cytosine arabinoside is 1.1: 1～2.0 * 10
3: 1.
Described enzyme is lipase, proteolytic enzyme or esterase.
Lipase derives from Candida antarctica, Thermomyces lanuginosus, Rhizomucormiehei, Burkholderia acepacia, Pseudomonas fluorescens, Aspergillus niger, Mucor miehei, Porcine pancreas or Human pancreas; Proteolytic enzyme derives from Aspergillusmelleus, Bacillus subilis, Bacillus lichemiformis; Esterase derives from Porcine liver.
5, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 3 is characterized in that the carbon chain lengths of fatty acid ester in the described carboxylicesters is C2～C24, contains 0～6 two key; Aromatic ester contains 1 or 1 above phenyl ring; The fatty acid carbons chain length of acid anhydrides is C3～C18.
Described organic solvent comprises one or more in alkanes, alcohols, ester class, ethers, ketone, the nitrogenous compound solvent.
Described hydro carbons refers to one or more in stable hydrocarbon, unsaturated hydrocarbons, the aromatic hydrocarbons; Alcohols refers to one or more in monohydroxy-alcohol, the polyvalent alcohol; Ethers refers to one or more in fatty ether, aryl oxide, diox, the tetrahydrofuran (THF); Ketone refer in aliphatic ketone, the arone one or more, the nitrogenous compound solvent refers in nitrile, amine, the pyridine one or more.
In (2) step, adopt following method to separate Cytarbine Ocfostate: after reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, and with methyl alcohol, ethanol organic solvent and re-crystallizing in ethyl acetate or through silica gel column chromatogram separating purification, promptly gets Cytarbine Ocfostate after the concentrated solution vacuum-drying.
The present invention has following advantage compared with prior art:
1. adopting efficiently, the biological catalyst enzyme comes the catalysis Cytarbine Ocfostate synthetic, enzymic catalytic reaction has high selectivity, product structure is easily controlled, byproduct of reaction is few, product Cytarbine Ocfostate purity height, the selectivity of traditional chemical method is low to cause substrate utilization ratio low owing to overcome, the shortcoming that product purity is low;
2. need not protect with going by radical protection, reaction process is simple and easy to control, and product is easily separated;
3. reaction conditions gentleness, environmental friendliness.
Embodiment
Embodiment 1
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 0.194g (2.26 * 10
-3Mol) reaction solution of vinyl-acetic ester, 10L pyridine joins in the tool plug triangular flask, then add 200U and derive from the lipase (30 of Candida antarctica, 000U/g), place vibration in 30 ℃, the constant temperature water bath vibrator of 100rpm under the normal pressure, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add dissolve with ethanol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification, with recrystallizing methanol, promptly get 0.527g (90%) cytosine arabinoside 5 '-acetic ester (optical purity reaches more than 98%) at last.
Embodiment 2
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 918g (4.10mol) vinyl laurate, the reaction solution of 50mL pyridine joins in the tool plug triangular flask, then add 2000U and derive from the lipase (30 of Candida antarctica, 000U/g), place 40 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 250rpm, behind the reaction 12h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethyl acetate and dissolve with methanol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification, with re-crystallizing in ethyl acetate, promptly get 0.77g (88%) cytosine arabinoside 5 '-laurate (optical purity reaches more than 98%) at last.
Embodiment 3
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 197g (5.16 * 10
-1Mol) tetracosa carbon acid methyl esters, 150mL N, the reaction solution of dinethylformamide joins in the tool plug triangular flask, then add 4000U and derive from the lipase (30 of Candida antarctica, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, the mixed solution dissolving that adds ethyl acetate and methyl alcohol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification,, promptly get 1.07g (88%) cytosine arabinoside 5 '-tetracosa carbon acid esters (optical purity reaches more than 98%) at last with re-crystallizing in ethyl acetate.
Embodiment 4
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 44.3g (5.16 * 10
-1Mol) vinyl acrylate, the reaction solution of the mixed solution of 5L pyridine and hexane adds in the tool plug triangular flask, then add 200U and derive from the lipase (250 of Human pancreas, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add acetic acid ethyl dissolution after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification, with ethyl alcohol recrystallization, promptly get 0.528g (90%) cytosine arabinoside 5 '-acrylate (optical purity reaches more than 98%) at last.
Embodiment 5
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 1402g (4.10mol) 4,7,10,13,16,19-docosenoic acid methyl esters, the reaction solution of the mixing solutions of 150mL pyridine and isopropyl ether adds in the tool plug triangular flask, then add 4000U and derive from the lipase (250 of Human pancreas, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm is behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, and adds dissolve with ethanol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification, with recrystallizing methanol, promptly get 0.98g (87%) cytosine arabinoside 5 '-docosene acid esters (optical purity reaches more than 98%) at last.
Embodiment 6
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 282g (5.16 * 10
-1Mol) oil anhydride, 1L N, the reaction solution of dinethylformamide adds in the tool plug triangular flask, derive from the lipase (1 of Mucor miehe in conjunction with adding 4000 U, 000U/g), place vibration in 60 ℃, the constant temperature water bath vibrator of 250rpm under the normal pressure, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add dissolve with ethanol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification,, promptly get 0.92g (88%) cytosine arabinoside 5 '-oleic acid acid esters (optical purity reaches more than 98%) at last with recrystallizing methanol.
Embodiment 7
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 29.4g (2.26 * 10
-1Mol) propionic anhydride, 150mL N, the reaction solution of the mixed solvent of dinethylformamide and octane adds in the tool plug triangular flask, then add 4000U and derive from the lipase (30 of Burkholderia acepaciai, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 4h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, the mixed solution dissolving that adds ethyl acetate and methyl alcohol after the concentrated solution vacuum-drying, through silica gel column chromatogram separating purification,, promptly get 0.55g (90%) cytosine arabinoside 5 '-propionic ester (optical purity reaches more than 98%) at last with re-crystallizing in ethyl acetate.
Embodiment 8
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 33.4g (2.26 * 10
-1Mol) vinyl benzoate, the reaction solution of the mixed solvent of 150mL pyridine and second eyeball adds in the tool plug triangular flask, then add 1000U and derive from the lipase (30 of Burkholderia acepaciai, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 24h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.643g (90%) cytosine arabinoside 5 '-benzoic ether (optical purity reaches more than 98%) at last.
Embodiment 9
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 33.4g (2.26 * 10
-1Mol) vinyl benzoate, the reaction solution of the mixed solution of 90mL pyridine and 60mL ionic liquid joins in the tool plug triangular flask, then add 600U and derive from the lipase (30 of Thermomyces lanuginosus, 000U/g), place 25 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 250rpm, behind the reaction 36h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.643g (90%) cytosine arabinoside 5 '-benzoic ether (optical purity reaches more than 98%) at last.
Embodiment 10
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 145g (4.10 * 10
-1Mol) naphthylacetic acid acid anhydride, the reaction solution of the mixed solution of 120mL second eyeball and 30mL ionic liquid adds in the tool plug triangular flask, then add 1000U and derive from the proteolytic enzyme (6 of Bacillus lichemiformis, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 4h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.761g (90%) cytosine arabinoside 5 '-naphthylacetic acid ester (optical purity reaches more than 98%) at last.
Embodiment 11
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 26.3g (2.05 * 10
-1Mol) valeric acid vinyl acetate, the reaction solution of 150mL tetrahydrofuran (THF) joins in the tool plug triangular flask, then add 300U and derive from the proteolytic enzyme (6 of Bacillus lichemiformis, 000U/g), place 30 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 100rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.606g (90%) cytosine arabinoside 5 '-valerate (optical purity reaches more than 98%) at last.
Embodiment 12
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 636g (2.05mol) stearic acid vinyl ester, the reaction solution of 150mL pyridine joins in the tool plug triangular flask, then add 4000U and derive from the proteolytic enzyme (6 of Bacillus lichemiformis, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 250rpm, behind the reaction 24h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, get 0.924g (88%) cytosine arabinoside 5 '-stearate (optical purity reaches more than 98%).
Embodiment 13
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 5.99g (2.05 * 10
-2Mol) 6,9,12-octadecenic acid methyl esters, the reaction solution of the mixed solution of 90mL tetrahydrofuran (THF) and 60mL ionic liquid adds in the tool plug triangular flask, then add 200U and derive from the proteolytic enzyme (1 of Aspergillus melleus, 500U/g), place 55 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 200rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.915g (88%) cytosine arabinoside 5 '-octadecylene acid esters (optical purity reaches more than 98%) at last.
Embodiment 14
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 1.23g (2.26 * 10
-3Mol) oil anhydride, 105mL N, the reaction solution of the mixed solution of dinethylformamide and 45mL ionic liquid adds in the tool plug triangular flask, derive from the esterase (15 of Porcine liver in conjunction with adding 4000U, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 250rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.92g (88%) cytosine arabinoside 5 '-oleic acid acid esters (optical purity reaches more than 98%) at last.
Embodiment 15
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 282g (5.16 * 10
-1Mol) oil anhydride, 105mL N, the reaction solution of the mixed solution of dinethylformamide and 45mL ionic liquid adds in the tool plug triangular flask, derive from the esterase (15 of Porcine liver in conjunction with adding 4000U, 000U/g), place 60 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 250rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.92g (88%) cytosine arabinoside 5 '-oleic acid acid esters (optical purity reaches more than 98%) at last.
Embodiment 16
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 665g (4.10mol) methyl cinnamate, 150mL N, the reaction solution of the mixed solvent of dinethylformamide and octane joins in the tool plug triangular flask, then add 2000U and derive from the proteolytic enzyme (1 of Aspergillus melleus, 500U/g), place 35 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 150rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.675g (88%) cytosine arabinoside 5 '-laurate (optical purity reaches more than 98%) at last.
Embodiment 17
To contain 0.5g (2.05 * 10
-3Mol) cytosine arabinoside, 334g (2.26 * 10
-3Mol) vinyl benzoate, the reaction solution of the mixed solvent of the 150mL pyridine and the trimethyl carbinol joins in the tool plug triangular flask, then add 2000U and derive from the proteolytic enzyme (1 of Aspergillus melleus, 500U/g), place 35 ℃ under the normal pressure, vibration in the constant temperature water bath vibrator of 150rpm, behind the reaction 48h, reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, add ethanol (perhaps ethyl acetate after the concentrated solution vacuum-drying, the mixed solution of methyl alcohol or ethyl acetate and methyl alcohol) dissolving, through silica gel column chromatogram separating purification, with methyl alcohol (perhaps ethanol or ethyl acetate) recrystallization, promptly get 0.714 (90%) cytosine arabinoside 5 '-benzoic ether (optical purity reaches more than 98%) at last.
Claims (8)
1, a kind of method of enzyme catalysis for preparing cytosine ester arabinoside is characterized in that adopting non-aqueous media, is acry radical donor with carboxylicesters or acid anhydrides, utilizes the enzyme catalysis cytosine arabinoside to carry out acylation reaction, the synthetic Cytarbine Ocfostate that obtains.
2, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 1 is characterized in that comprising the steps:
(1) in reactor, adds cytosine arabinoside, non-aqueous media, carboxylicesters or acid anhydrides successively;
(2) being that the ratio of 100～4000U/ gram cytosine arabinoside adds enzyme in enzyme dosage, is that 25～60 ℃, hunting speed are to react under 100～250rpm/min, the condition 1～48 hour in temperature, separates obtaining Cytarbine Ocfostate;
Described non-aqueous media comprises that organic solvent system or ionic liquid content are the organic solvent and the mixed system of ionic liquid of 0～40% quality, and consumption is 0.5～10L/ gram cytosine arabinoside; The mol ratio of described carboxylicesters or acid anhydrides and cytosine arabinoside is 1.1: 1～2.0 * 10
3: 1.
3, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 1 and 2 is characterized in that described enzyme is lipase, proteolytic enzyme or esterase.
4, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 3 is characterized in that described lipase derives from Candida antarctica, Thermomyces lanuginosus, Rhizomucormiehei, Burkholderia acepacia, Pseudomonas fluorescens, Aspergillus niger, Mucor miehei, Porcine pancreas or Human pancreas; Proteolytic enzyme derives from Aspergillusmelleus, Bacillus subilis, Bacillus lichemiformis; Esterase derives from Porcine liver.
5, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 3 is characterized in that the carbon chain lengths of fatty acid ester in the described carboxylicesters is C2～C24, contains 0～6 two key; Aromatic ester contains 1 or 1 above phenyl ring; The fatty acid carbons chain length of acid anhydrides is C3～C18.
6, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 3 is characterized in that described organic solvent comprises one or more in alkanes, alcohols, ester class, ethers, ketone, the nitrogenous compound solvent.
7, the method for enzyme catalysis for preparing cytosine ester arabinoside according to claim 6 is characterized in that described hydro carbons refers to one or more in stable hydrocarbon, unsaturated hydrocarbons, the aromatic hydrocarbons; Alcohols refers to one or more in monohydroxy-alcohol, the polyvalent alcohol; Ethers refers to one or more in fatty ether, aryl oxide, diox, the tetrahydrofuran (THF); Ketone refer in aliphatic ketone, the arone one or more, the nitrogenous compound solvent refers in nitrile, amine, the pyridine one or more.
8, according to the method for claim 5 or 6 described enzyme catalysis for preparing cytosine ester arabinoside, it is characterized in that in (2) step, adopt following method to separate Cytarbine Ocfostate: after reaction mixture is dezymotized after filtration, vacuum-evaporation concentrates, with methyl alcohol, ethanol organic solvent and re-crystallizing in ethyl acetate or through silica gel column chromatogram separating purification, promptly get Cytarbine Ocfostate after the concentrated solution vacuum-drying.
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| CNB200410077504XA CN1300326C (en) | 2004-12-22 | 2004-12-22 | Method of enzyme catalysis for preparing cytosine ester arabinoside |
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|---|---|---|---|
| CNB200410077504XA CN1300326C (en) | 2004-12-22 | 2004-12-22 | Method of enzyme catalysis for preparing cytosine ester arabinoside |
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| CN1300326C CN1300326C (en) | 2007-02-14 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250209B (en) * | 2007-03-27 | 2012-02-22 | 沈阳药科大学 | Alexan 5'-O-amino acid ester hydrochloride and preparation method thereof |
| CN102952770A (en) * | 2012-11-12 | 2013-03-06 | 华南理工大学 | Preparation method for cell catalyst with high regioselective acylation activity and microbiologic method for synthesizing cytosine arabinoside monoester |
| CN104593445A (en) * | 2015-01-21 | 2015-05-06 | 深圳大学 | Method for synthesizing sucrose fatty acid ester |
| CN106868077A (en) * | 2016-12-29 | 2017-06-20 | 河南科技学院 | A kind of preparation method of the phloridzin triethyl with hepatoma Hep G 2 cells inhibitory activity |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69108014T2 (en) * | 1990-03-13 | 1995-07-06 | Acic Canada Inc | METHOD FOR PRODUCING NUCLEOSIDES AND THEIR ANALOGS. |
-
2004
- 2004-12-22 CN CNB200410077504XA patent/CN1300326C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250209B (en) * | 2007-03-27 | 2012-02-22 | 沈阳药科大学 | Alexan 5'-O-amino acid ester hydrochloride and preparation method thereof |
| CN102952770A (en) * | 2012-11-12 | 2013-03-06 | 华南理工大学 | Preparation method for cell catalyst with high regioselective acylation activity and microbiologic method for synthesizing cytosine arabinoside monoester |
| CN104593445A (en) * | 2015-01-21 | 2015-05-06 | 深圳大学 | Method for synthesizing sucrose fatty acid ester |
| CN106868077A (en) * | 2016-12-29 | 2017-06-20 | 河南科技学院 | A kind of preparation method of the phloridzin triethyl with hepatoma Hep G 2 cells inhibitory activity |
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|---|---|
| CN1300326C (en) | 2007-02-14 |
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