CN107384779A - A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis - Google Patents
A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis Download PDFInfo
- Publication number
- CN107384779A CN107384779A CN201610326543.1A CN201610326543A CN107384779A CN 107384779 A CN107384779 A CN 107384779A CN 201610326543 A CN201610326543 A CN 201610326543A CN 107384779 A CN107384779 A CN 107384779A
- Authority
- CN
- China
- Prior art keywords
- reaction
- uridines
- acetyl
- channel
- uridine
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/18—Apparatus specially designed for the use of free, immobilized or carrier-bound enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/38—Nucleosides
- C12P19/385—Pyrimidine nucleosides
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Sustainable Development (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention discloses a kind of method of lipase-catalyzed online synthesis 5'O acetyl uridines.Methods described includes:Using volume ratio as 1:8~16 dimethyl sulfoxide and tert-pentyl alcohol is reaction dissolvent, using mol ratio as 1:5~13 uridine and vinyl acetate are raw material; using 0.5~1.0g Lipozymes TLIM as catalyst; raw material and reaction dissolvent are placed in syringe; Lipozyme TLIM is uniformly filled in the reaction channel of microfluidic channel reactor; raw material and reaction dissolvent is continuously passed through in reaction channel under the promotion of syringe pump and carry out acylation reaction; the reaction channel internal diameter of the microfluidic channel reactor is 0.8~2.4mm, a length of 0.5~1.0m of reaction channel;It is 15~50 DEG C to control acylation reaction temperature, and the acylation reaction time is 20~35min, collects reaction solution online by product collector, reaction solution obtains 5'O acetyl uridines through conventional post processing.The present invention has the advantages of reaction time is short, selectivity is high and yield is high.
Description
(1) technical field
The present invention relates to a kind of method of lipase-catalyzed online controllable selectivity synthesis 5'-O- acetyl uridines
(2) background technology
Nucleoside medicine occupies an important position in the treatment of viral disease.Clinically use at present disease-resistant
In cytotoxic drug, nucleoside medicine proportion is up to more than 60%.Most nucleoside class compound is polyhydroxy chemical combination
Thing, has that polarity is higher, intestinal permeability is relatively low, and fat-soluble poor, toxic side effect is big and oral bioavailability
Spend the defects of relatively low.After nucleoside compound is by being esterified modification, its fat-soluble, raising pharmacological activity can be strengthened,
Improve its oral administration biaavailability.In common chemical method esterification process, multiple hydroxyls are likely to participate in ester
Change, product is the mixture of monoesters and polyester, thus needs through " radical protection -- esterification -- is deprotected group " three
Step could obtain the product of single position esterification.And enzyme has good selectivity and selectivity to substrate, Ke Yixuan
Selecting property is esterified to some hydroxyl of nucleosides, and reaction selectivity is higher, reduces the difficulty of product later separation,
Therefore biocatalysis technology plays more and more important role in the esterification of nucleoside compound.
It is micro-fluidic learn (Microfluidics) be in micron scale construction manipulation nanoliter to picoliters volume fluid technology
It is the new cross discipline to emerge rapidly nearly ten years with science.Currently, the development of micro-fluidic surmounts significantly
The purpose of original predominantly analytical chemistry service, and turn into whole chemistry subject, life science, instrument
The important technological platform of device science or even information science new round innovation research.
A first piece, which has been delivered, from Harrison seminars in 1997 in micro-fluidic chip microreactor synthesizes compound
Document after, micro-fluidic chip reactor has been successfully used to a variety of organic synthesis, and illustrates extensive
Application prospect.With the development of microring array, micro-reacting tcchnology in micro-fluidic chip, carry out synthesizing instead in the chips
One of the study hotspot in micro-fluidic chip field should be had become.
Compared with conventional chemical reactor, micro passage reaction not only has and makes diffusion length between reactant significantly
Shorten, and mass transfer velocity is fast;The reaction conditions such as reactant ratio, temperature, reaction time and flow velocity are easily controlled
System, side reaction are less;Need reactant dosage little, can not only reduce expensive, poisonous, adverse reaction thing
Dosage, caused environmental contaminants are also few in course of reaction, are a kind of environment-friendly, study on the synthesis novel substances
Technology.
At present, more domestic and foreign scholars carry out the Enzyme catalyzed synthesis of nucleosides acylation reaction in organic media
Research, but this method is catalyzed from acylase more, generally requires the longer reaction time (12-24h),
And the conversion ratio of reaction and selectivity be not high, therefore we have studied lipase-catalyzed online in micro passage reaction
The method for synthesizing 5'-O- acetyl uridines, it is intended to find a kind of the online controllable of the 5'-O- acetyl uridines of high-efficiency environment friendly
Method for selective synthesis.
(3) content of the invention
The technical problem to be solved in the present invention is to provide lipase-catalyzed online in a kind of microfluidic channel reactor
The new technology of 5'-O- acetyl uridines is synthesized, there is the advantages of reaction time is short, yield is high, selectivity is good.
In order to solve the above technical problems, the present invention adopts the following technical scheme that:
A kind of method of lipase-catalyzed online synthesis 5'-O- acetyl uridines, methods described use microfluidic channel
Reactor, described microfluidic channel reactor include syringe pump, syringe, reaction channel and product collector,
The syringe is installed in syringe pump, is connected by an interface with reaction channel entrance, the collection of products
Device is connected by an interface and reaction channel outlet, and the reaction channel internal diameter is 0.8~2.4mm, and reaction is logical
A length of 0.5~the 1.0m in road;Methods described includes:Using volume ratio as 1:8~16 dimethyl sulfoxide (DMSO) and
Tert-pentyl alcohol is reaction dissolvent, using mol ratio as 1:5~13 uridine and vinyl acetate are raw material, with 0.5~1.0g
Lipozyme TLIM is catalyst, and raw material and reaction dissolvent are placed in syringe, by lipase
Lipozyme TLIM are uniformly filled in reaction channel, connect raw material and reaction dissolvent under the promotion of syringe pump
Continuous be passed through in reaction channel carries out acylation reaction, makes the concentration of uridine in reaction system (raw material+reaction dissolvent)
For 0.03~0.07mmol/mL, it is 15~50 DEG C to control acylation reaction temperature, and the acylation reaction time is 20~35min,
Reaction solution is collected by product collector online, reaction solution obtains 5'-O- acetyl uridines through conventional post processing.
In the microfluidic channel reactor that the present invention uses, the syringe number can be one or more, depending on
Depending on specific reaction requirement.For example when using two syringes, T-shaped or Y type interfaces can be used to make not
Same reactant introduces from two entrances, confluxes into public reaction channel, passes through the middle reactant of microchannel
Molecule contacts increase with collision probability, two bursts of reaction liquid streams is mixed and is reacted in public reaction channel.
Described microfluidic channel reactor also includes insulating box, and described reaction channel is placed in insulating box, with
This can effective controlling reaction temperature.Described insulating box can voluntarily select according to reaction temperature requirement, such as
Constant temperature water box etc..
The present invention is unlimited for the material of reaction channel, it is recommended to use green, the material of environmental protection, such as silicone tube;
Shape for reaction channel is preferably shaped form, it is ensured that reaction solution stably passes through.
The present invention first dissolves uridine in implementation process with DMSO, is further continued for plus tert-pentyl alcohol is to certain volume,
Loaded on standby in syringe;Then vinyl acetate is dissolved to certain volume with tert-pentyl alcohol, loaded on another syringe
In it is standby;Finally raw material and reaction dissolvent is set to be passed through instead under syringe pump (such as the syringe pumps of PD 1200) promotion
Answer in passage and reacted.
In the present invention, described Lipozyme TLIM is given birth to using letter (Novozymes) company of Novi
The commodity of production, it is a kind of by microorganism preparation, 1,3 position-specifics, food-grade lipase (EC3.1.1.3)
Preparation on particle silica gel.It is being obtained from Thermomyceslanuginosus, gene-modified with one kind
Aspergillus oryzae (Aspergillusoryzae) microorganism is by submerged fermentation production.
Further, the volume ratio of dimethyl sulfoxide and tert-pentyl alcohol is preferably 1 in the reaction dissolvent:12~1:16, preferably
For 1:14.
Further, the mol ratio of the uridine and vinyl acetate is preferably 1:7~13, more preferably 1:9~11, most
Preferably 1:9.
Further, the concentration of uridine is preferably 0.04~0.06mmol/mL in reaction system, is most preferably
0.05mmol/mL。
Further, the acylation reaction temperature is preferably 20~40 DEG C, most preferably 30 DEG C.
Further, the acylation reaction time is preferably 25~35min, most preferably 30min.
The reaction product of the present invention can collect online, and gained reaction solution can pass through conventional post-processing approach
Obtain 5'-O- acetyl uridines.The conventional post-processing approach can be:It is molten that gained reaction solution is evaporated under reduced pressure removing
Agent, with 200-300 mesh silica gel wet method dress posts, elution reagent is ethyl acetate:Methanol=20:1, sample is with a small quantity
Wet method upper prop after elution reagent dissolving, eluent, while TLC tracking elution processes are collected, is contained what is obtained
The eluent for having single product, which merges, to be evaporated, and can obtain white solid, as 5'-O- acetyl uridine.
Compared with prior art, beneficial effects of the present invention are:The present invention utilizes in microfluidic channel reactor
Lipase-catalyzed online synthesis 5'-O- acetyl uridines, the method not only significantly shortens the reaction time, and has
There are high conversion ratio and selectivity;Utilize economic Lipozyme TLIM catalysis nucleosides first simultaneously
Esterification, reaction cost is reduced, the advantage with economical and efficient.
(4) illustrate
Fig. 1 is the structural representation for the microfluidic channel reactor that the embodiment of the present invention uses.
(5) embodiment
Protection scope of the present invention is described further with specific embodiment below, but protection scope of the present invention
Not limited to this:
The structural reference Fig. 1 for the microfluidic channel reactor that the embodiment of the present invention uses, including a syringe pump
(not shown), two syringes 1 and 2, reaction channel 3, constant temperature water box (5, only show that its plane is shown
It is intended to) and product collector 4;Two syringes 1 and 2 are installed in syringe pump, pass through a Y type interface
It is connected with the entrance of reaction channel 3, the reaction channel 3 is placed in constant temperature water box 5, passes through constant temperature water box
5 controlling reaction temperatures, the internal diameter 2.0mm of described reaction channel 3, pipe range 1m, the reaction channel 3
Outlet is connected by an interface with product collector 4.
Embodiment 1:The synthesis of 5'-O- acetyl uridines
Device is with reference to figure 1:Uridine (1.0mmol) is dissolved in 1.33mLDMSO and 8.67mL tert-pentyl alcohols
In, vinyl acetate (9.0mmol) is dissolved in 10mL tert-pentyl alcohols, is then injected respectively loaded on 10mL
It is standby in device.0.87g Lipozymes TLIM is uniformly filled in reaction channel, is injected in PD 1200
Under pump promotes, two-way reaction solution is respectively with 10.4 μ Lmin-1Flow velocity by " Y " joint enter reaction channel in
Reacted, temperature of reactor is controlled at 30 DEG C by constant temperature water box, reaction solution continuous stream in reaction channel
Dynamic reaction 30min, reaction result pass through thin-layer chromatography TLC tracing detections.
Reaction solution is collected by product collector online, is evaporated under reduced pressure and removes solvent, it is wet with 200-300 mesh silica gel
Method fills post, and elution reagent is ethyl acetate:Methanol=20:1, pillar height 35cm, column diameter 4.5cm, sample is with less
Wet method upper prop after elution reagent dissolves is measured, eluent collects flow velocity 2mLmin-1, while TLC tracking elutions
Process, the obtained eluent containing single product is merged and is evaporated, obtains white solid, obtains 5'-O- second
Ureide glycosides, HPLC detection uridines conversion ratio 85%, selectivity 98%.
Nuclear-magnetism characterization result is as follows:
1H-NMR(DMSO-d6,δ,ppm):11.36(s,H3), 7.62 (d, J=9Hz, H6), 5.75 (d, 1H, J=
4.5Hz,H1'), 5.67 (d, 1H, J=9Hz, H5), 5.48 (d, 1H, J=5.5Hz, 3'-OH), 5.28 (d, 1H, J
=5.5Hz, 2'-OH), 4.90 (dd, 1H, J=1.5Hz, J=14Hz, CH=C-O), 4.65 (dd, 1H, J=
1.5Hz, J=6Hz, CH=C-O), 4.24 (m, 2H, H2'+H3'),4.07(m,1H,H4'),3.98(m,2H,
H5'),2.05(s,3H,H2”).
13C NMR(DMSO-d6,ppm):170.17(C1”),163.04(C4),150.60(C2),140.76(C6),
102.02(C5),88.76(C1'),81.04(C4'),72.65(C3'),69.77(C2'),63.72(C5'),20.61(C2”).
Embodiment 2-6
Change organic solvent volume ratio in microfluidic channel reactor, it is 50 DEG C to control temperature, and other are the same as implementation
Example 1, reaction result is as shown in table 1:
Table 1:Organic solvent compares the influence of reaction
The result of table 1 shows, when flow velocity is 10.4 μ Lmin-1, the reaction time is 30min, reaction temperature
It it is 50 DEG C, reactant uridine and vinyl acetate mol ratio are 1:9, uridine concentration is in reaction system
During 0.05mmol/mL, conversion ratio increases with organic solvent volume in reactor than increase, works as DMSO:Uncle
Amylalcohol volume ratio reaches 1:Reach optimal when 14, being further continued for increase volume ratio will cause reactant dissolving endless
Reduce conversion ratio entirely.So optimal organic solvent volume ratio is in micro-fluidic micro passage reaction in the present invention
1:14。
Embodiment 7-11
Change the substrate mol ratio of uridine and vinyl acetate in micro-fluidic micro passage reaction, control temperature
50 DEG C, other are with embodiment 1, as a result as shown in table 2:
Table 2:Uridine and influence of the vinyl acetate substrate mol ratio to reaction
The result of table 2 shows, when flow velocity is 10.4 μ Lmin-1, the reaction time is 30min, reaction temperature
It is 50 DEG C, organic solvent DMSO in reactor:Tert-pentyl alcohol volume ratio is 1:14, uridine in reaction system
When concentration is 0.05mmol/mL, with the increase of reactant vinyl acetate, the conversion ratio of reaction also with
Increase, when substrate mol ratio is 1:When 9, the conversion ratio of reaction is optimal, so micro-fluidic micro- logical in the present invention
Optimal substrate mol ratio is 1 in road reactor:9.
Embodiment 12-15
Change the temperature of microfluidic channel reactor, with embodiment 1, reaction result is as shown in table 3 for other:
Table 3:Influence of the temperature to reaction
The result of table 3 shows, when flow velocity is 10.4 μ Lmin-1, the reaction time is 30min, in reactor
Organic solvent DMSO:Tert-pentyl alcohol volume ratio is 1:14, reactant uridine is with vinyl acetate mol ratio
1:9, when uridine concentration is 0.05mmol/mL in reaction system, when reaction temperature is in 30 DEG C, reaction
Conversion ratio it is optimal, temperature or Tai Gao or the too low activity that will all influence enzyme.It is so micro-fluidic micro- logical in the present invention
Optimum temperature is 30 DEG C in road reactor.
Embodiment 16-18
Change the reaction time of microfluidic channel reactor, with embodiment 1, reaction result is as shown in table 4 for other:
Table 4:Influence of the reaction time to reaction
The result of table 3 shows, as organic solvent DMSO in reactor:Tert-pentyl alcohol volume ratio is 1:14, instead
It is 1 to answer thing uridine and vinyl acetate mol ratio:9, reaction temperature is 30 DEG C, and uridine is dense in reaction system
When degree is 0.05mmol/mL, when reacted between when be 30min, reaction conversion ratio 85%, reach
To optimal.So optimum reacting time is 30min in micro-fluidic micro passage reaction in the present invention.
Embodiment 19-22
Change the concentration of microfluidic channel reactant, with embodiment 1, reaction result is as shown in table 5 for other:
Table 5:Influence of the reactant concentration to reaction
The result of table 5 shows, as organic solvent DMSO in reactor:Tert-pentyl alcohol volume ratio is 1:14, instead
It is 1 to answer thing uridine and vinyl acetate mol ratio:9, reaction temperature is 30 DEG C, and the reaction time is 30
Min, when uridine concentration is 0.05mmol/mL in reaction system, reaction conversion ratio is up to 85%, so
Optimum response thing concentration is 0.05mmol/mL in micro-fluidic micro passage reaction in the present invention.
Comparative example 1-3
Change the catalyst in micro-fluidic micro passage reaction, it is (right to be changed to Lipozyme RM IM respectively
Ratio 1), lipase Novozym 435 (comparative example 2), bacillus alkaline protease (comparative example 3),
Other are with embodiment 1, as a result as shown in table 6.
Table 6:Influence of the different enzymes to reaction conversion ratio and selectivity
The result of table 6 shows, for the regioselectivity esterification of enzymatic uridine in microfluidic channel reactor
For, different enzymes has fairly obvious influence to reaction.It is catalyzed using Lipozyme RMIM
Reaction, the conversion ratio of 5'-O- acetyl uridines is 38%.And the reaction is catalyzed using bacillus alkaline protease,
The conversion ratio of 5'-O- acetyl uridines is only 5%.In terms of the result of table 6, for enzyme in microfluidic channel reactor
For the regioselectivity esterification for promoting uridine, maximally effective catalyst is Lipozyme TLIM,
The conversion ratio of uridine is 85%, and selectivity is 98%.
Comparative example 4-5
Change different types of uridine compound in micro-fluidic micro passage reaction, by the uridine of embodiment 1
1mmol be changed to respectively guanosine 1mmol (comparative example 4), 3'- BrdUs 1mmol (comparative example 5), other
With embodiment 1, as a result as shown in table 7.
Table 7:Influence of the different nucleoside compounds to reaction
The result of table 7 shows, for the regioselectivity of enzymatic nucleoside compound in microfluidic channel reactor
For esterification, different nucleoside compounds has different reaction results.3'- BrdUs are same
Under reaction condition, conversion ratio is only 17%, and reaction is relatively difficult.The reaction result of guanosine is also undesirable, conversion
Rate is only 23%.In terms of the result of table 7, for the area of enzymatic nucleoside compound in microfluidic channel reactor
For field selectivity esterification, uridine can obtain more satisfactory reaction result, and the conversion ratio of reaction can be with
Reach 85%, selectivity is 98%.
Claims (7)
- A kind of 1. method of lipase-catalyzed online synthesis 5'-O- acetyl uridines, it is characterised in that methods described is adopted With microfluidic channel reactor, described microfluidic channel reactor includes syringe pump, syringe, reaction channel And product collector, the syringe are installed in syringe pump, it is connected by an interface with reaction channel entrance, The product collector is connected by an interface and reaction channel outlet, and the reaction channel internal diameter is 0.8~2.4mm, a length of 0.5~1.0m of reaction channel;Methods described includes:Using volume ratio as 1:The two of 8~16 First sulfoxide and tert-pentyl alcohol are reaction dissolvent, using mol ratio as 1:5~13 uridine and vinyl acetate are raw material, Using 0.5~1.0g Lipozymes TLIM as catalyst, raw material and reaction dissolvent are placed in syringe, Lipozyme TLIM is uniformly filled in reaction channel, make under the promotion of syringe pump raw material and Reaction dissolvent, which is continuously passed through in reaction channel, carries out acylation reaction, and the concentration for making uridine in reaction system is 0.03~0.07mmol/mL, it is 15~50 DEG C to control acylation reaction temperature, and the acylation reaction time is 20~35min, Reaction solution is collected by product collector online, reaction solution is post-treated to obtain 5'-O- acetyl uridines.
- 2. the method for lipase-catalyzed online synthesis 5'-O- acetyl uridines as claimed in claim 1, its feature It is:Described method comprises the following steps:Uridine first is dissolved with dimethyl sulfoxide, then adds tert-pentyl alcohol to certain body Product, loaded on standby in syringe;Vinyl acetate is dissolved to certain volume with tert-pentyl alcohol, loaded on another syringe In it is standby;Then raw material and reaction dissolvent is made to be passed through in reaction channel and be reacted under syringe pump promotion.
- 3. the method for lipase-catalyzed online synthesis 5'-O- acetyl uridines as claimed in claim 1, its feature It is:The microfluidic channel reactor includes insulating box, and the reaction channel is placed in insulating box.
- 4. the method for lipase-catalyzed online synthesis 5'-O- acetyl uridines as claimed in claim 2, its feature It is:The microfluidic channel reactor includes insulating box, and the reaction channel is placed in insulating box.
- 5. the method for the lipase-catalyzed online synthesis 5'-O- acetyl uridines as described in one of Claims 1 to 4, It is characterized in that:The volume ratio of dimethyl sulfoxide and tert-pentyl alcohol is 1 in the reaction system:12~16, the uridine Mol ratio with vinyl acetate is 1:7~13, the concentration for making uridine in reaction system is 0.04~0.06mmol/mL, the acylation reaction temperature are 20~40 DEG C, and the acylation reaction time is 25~35min.
- 6. the method for lipase-catalyzed online synthesis 5'-O- acetyl uridines as claimed in claim 5, its feature It is:The mol ratio of the uridine and vinyl acetate is 1:9~11.
- 7. the method for lipase-catalyzed online synthesis 5'-O- acetyl uridines as claimed in claim 6, its feature It is:The volume ratio of dimethyl sulfoxide and tert-pentyl alcohol is 1 in the reaction system:14, the uridine and vinyl acetate The mol ratio of ester is 1:9, the concentration for making uridine in reaction system is 0.05mmol/mL, the acylation reaction temperature Spend for 30 DEG C, the acylation reaction time is 30min.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610326543.1A CN107384779A (en) | 2016-05-17 | 2016-05-17 | A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610326543.1A CN107384779A (en) | 2016-05-17 | 2016-05-17 | A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107384779A true CN107384779A (en) | 2017-11-24 |
Family
ID=60338725
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610326543.1A Pending CN107384779A (en) | 2016-05-17 | 2016-05-17 | A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107384779A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103184257A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method for on-line synthesizing sucrose-6-acetate catalyzed by lipase |
CN103184252A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method of using lipase to catalyze and synthesize glucose-6-laurate on line |
CN103184249A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method for on-line synthesizing glucose-6-palmitate by lipase catalysis |
-
2016
- 2016-05-17 CN CN201610326543.1A patent/CN107384779A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103184257A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method for on-line synthesizing sucrose-6-acetate catalyzed by lipase |
CN103184252A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method of using lipase to catalyze and synthesize glucose-6-laurate on line |
CN103184249A (en) * | 2011-12-31 | 2013-07-03 | 浙江工业大学 | Method for on-line synthesizing glucose-6-palmitate by lipase catalysis |
Non-Patent Citations (4)
Title |
---|
HUAI WANG等: "Novel and highly regioselective route for synthesis of 5-fluorouridine lipophilic ester derivatives by lipozyme TL IM", 《JOURNAL OF BIOTECHNOLOGY》 * |
李宁: "脂肪酶催化5-氟-2'-脱氧尿苷及其类似物区域选择性酰化反应的研究", 《道客巴巴数据库》 * |
熊小龙等: "脂肪酶催化药物合成的研究进展", 《化学与生物工程》 * |
罗伯茨等: "《精细化学品合成的生物催化》", 30 September 2007 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105838600B (en) | A kind of method of 5 ' O palmityl uridines of lipase-catalyzed online synthesis | |
CN107384991A (en) | A kind of method of 5 '-O- ethene adipyl uridines of lipase-catalyzed online synthesis | |
CN107384992A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- lauroyl -5-methyl-uridin | |
CN107384781A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- ethene adipyls -5-methyl-uridin | |
CN107475330A (en) | A kind of method of lipase-catalyzed online synthesis N (5 glucose ester valeryl) metoprolol | |
CN103667402B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-naringin ester | |
CN107488683A (en) | A kind of lipase-catalyzed online synthesis N(5 vinyl acetate valeryls)The method of mexiletine | |
CN103667396B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-naringin dihydrochalcone ester | |
CN103184249A (en) | Method for on-line synthesizing glucose-6-palmitate by lipase catalysis | |
CN107384782A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- ethene adipyls -5-FUD | |
CN103184252A (en) | Method of using lipase to catalyze and synthesize glucose-6-laurate on line | |
CN103184255A (en) | Method of using lipase to catalyze and synthesize galactose-6-acetate on line | |
CN107488690A (en) | A kind of method of lipase-catalyzed online synthesis N (5 glucose ester valeryl) mexiletine | |
CN107488691A (en) | A kind of method of lipase-catalyzed online synthesis N (5 lauroyl mannoses valeryl) metoprolol | |
CN107475329A (en) | A kind of method of lipase-catalyzed online synthesis N (5 sucrose ester valeryl) mexiletine | |
CN103667400B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-palmityl-naringin ester | |
CN103667393B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-palmityl-neohesperidin dihydrochalcone ester | |
CN105838599B (en) | A kind of method of 5 '-O- lauroyl uridines of lipase-catalyzed online synthesis | |
CN107384994A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- acetyl -5-FUD | |
CN103667394B (en) | A kind of lipase-catalyzed online synthesis 6 " method of-O-lauroyl-neohesperidin dihydrochalcone ester | |
CN107418989A (en) | A kind of method of lipase-catalyzed online synthesis N (5 sucrose ester valeryl) metoprolol | |
CN107384780A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- lauroyl -5-FUD | |
CN107384993A (en) | A kind of method of lipase-catalyzed online synthesis 5 '-O- acetyl -5-methyl-uridin | |
CN107384779A (en) | A kind of method of 5 '-O- acetyl uridines of lipase-catalyzed online synthesis | |
CN107604024A (en) | A kind of method of lipase-catalyzed online synthesis N (5 lauroyl mannoses valeryl) mexiletine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171124 |