CN104805158A - Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis - Google Patents
Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis Download PDFInfo
- Publication number
- CN104805158A CN104805158A CN201410034533.1A CN201410034533A CN104805158A CN 104805158 A CN104805158 A CN 104805158A CN 201410034533 A CN201410034533 A CN 201410034533A CN 104805158 A CN104805158 A CN 104805158A
- Authority
- CN
- China
- Prior art keywords
- lipase
- diphenyl ethylene
- synthetic method
- glycosides derivatives
- reaction
- 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
- 0 C=C[C@](CCC[N+]([O-])=O)*=* Chemical compound C=C[C@](CCC[N+]([O-])=O)*=* 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
The present invention discloses a synthesis method of a stilbene-glucoside derivative represented by a structure formula (I), wherein stilbene-glucoside and an organic acid RCOOH react in the presence of an immobilized lipase, and R is substituted or unsubstituted alkyl, an alkenyl, aryl, and a heterocyclic group. According to the present invention, the enzymatic synthesis is adopted, such that the reaction specificity is high, the process is simple, and the yield is high; the catalyst is separated from the substrate and the product, and can be reused repeatedly, such that the catalyst residue problem does not exist; and the whole process has characteristics of mild conditions and environmental protection. The formula (I) is defined in the instruction.
Description
Technical field
The present invention relates to a kind of method that biocatalysis prepares diphenyl ethylene glycosides derivatives, belong to biocatalysis and biosynthesis technology field.
Background technology
In recent years, the polyphenolic compound being representative with natural flavonoid and diphenylethylene, acts on because it has good anti-oxidant, anti-inflammatory, anti-apoptotic etc. and is subject to the extensive concern of international pharmacology educational circles.Stilbene glucoside (tetrahydroxystilbene glucoside, TSG), chemical name is 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-Glucose glycosides, it is the water soluble component of a kind of polyphenol structure that extraction and isolation obtains from Tuber Fleeceflower Root, white amorphous powder, molecular weight is 406.39.Study effects such as showing TSG has oxidation and removing free radicals, antitumor, reduction cholesterol, suppression artery congee sample shape harden, control senile dementia, raising memory function, vasodilator, protection liver, be widely used in the fields such as medicine, food, makeup.But, due to TSG less stable, easily oxidized in preservation and use procedure, greatly limit its some bioactive application.Therefore, by carrying out structure of modification to TSG, it is very necessary for finding active and that stability is stronger TSG derivative.
Carrying out structure of modification to natural product adopts chemical synthesis mostly at present, and TSG is polyol, it contains 3 phenolic hydroxyl groups, 3 secondary hydroxyl groups and 1 primary hydroxyl group, hydroxyl when utilizing chemical synthesis in TSG is all esterified, selectivity and the specificity of reaction are very poor, and research shows to only have in TSG molecule, and primary hydroxyl is esterified just has better biological activity afterwards.In addition, owing to using a large amount of organic solvent and catalyzer in reaction process, not only there is larger harm to environment, in product, also may remain poisonous chemical substance.Comparatively speaking, biocatalysis rule has higher group selectivity and specificity, the advantage that productive rate is high, by product is few, reaction conditions is gentle, environmental pollution is little.Therefore, through biological catalysis research and development TSG derivative new synthetic process, there is important practice significance.
Summary of the invention
The object of the present invention is to provide a kind of biological catalysis to prepare the method for diphenyl ethylene glycosides derivatives, this method technique is simple, and reaction conditions is gentle, stable yield, environmental friendliness.
The synthetic method of diphenyl ethylene glycosides derivatives shown in structural formula (I), is obtained by reacting diphenyl ethylene glycosides derivatives shown in structural formula (I) with stilbene glucoside and organic acid RCOOH under immobilized lipase exists,
R is the alkyl of C1 ~ C17, the thiazolinyl of C2 ~ C22, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic radical, the alkyl of C1 ~ C17 that hydroxyl, carbonyl, replacement or unsubstituting aromatic yl replace, the thiazolinyl of C2 ~ C22 that hydroxyl, carbonyl, replacement or unsubstituting aromatic yl replace;
The above-mentioned substituting group related to is alkyl, the thiazolinyl of C2 ~ C5, hydroxyl, the alkoxyl group of C1 ~ C5, halogen radical, the carbonyl of C1 ~ C4.
Above-mentioned R is preferably following substituting group,
。
In above-mentioned reaction, immobilized lipase is selected from immobilization novozym 435, Lipozyme TL IM, Lipase PS-C, Lipase PS IM, Lipozyme IM, Lipase PS-D, Lipase R, Lipase G, Lipase OF, Lipase A, Lipase M, Lipase PEL; The mol ratio of stilbene glucoside and organic acid RCOOH is 1:5-1:12; Reaction is carried out in organic solvent, and described organic solvent is selected from THF, MeTHF, acetone, methylene dichloride, benzene, the trimethyl carbinol, toluene, acetonitrile, chloroform, ethyl acetate, N-BUTYL ACETATE; Temperature of reaction is 40 ~ 55 DEG C.
Add 4 molecular sieves after above-mentioned reaction completes and continue reaction, judge reaction end with thin layer chromatography.
Advantage of the present invention is as follows:
1, the present invention adopts enzymatic clarification, and reaction specificity is high, and technique is simple, and productive rate is high;
2, catalyzer is easy to and substrate and product separation, and can reuse, and there is not the problem of catalyst residue;
3, whole processing condition are gentle, environmental friendliness.
Embodiment
Get high purity 4 mmol TSG and organic acid (as acetic acid, valeric acid, lauric acid, forulic acid, vinylformic acid, one in methacrylic acid) put into the round-bottomed flask of 250ml, the mol ratio of TSG and acid is 1:5-1:12, add 100ml anhydrous organic solvent (THF, MeTHF, acetone, methylene dichloride, benzene, the trimethyl carbinol, toluene, acetonitrile, chloroform, ethyl acetate, one or more in N-BUTYL ACETATE), mix and be placed on preheating 15min(40-55 DEG C in constant temperature oscillator, 200 r/min), add immobilized lipase (the immobilization novozym 435 of 15-23mg/ml, Lipozyme TL IM, Lipase PS-C, Lipase PS IM, Lipozyme IM, Lipase PS-D, Lipase R, Lipase G, Lipase OF, Lipase A, one in Lipase M and PEL) start reaction, add 90-120 mg/ml 4 molecular sieve after 24h and continue reaction, reaction end is judged with thin layer chromatography.Gained mixture filters, and steams to desolventize to obtain crude product, obtains object product through silica gel column chromatography.
Embodiment 1
Get purity be 98% TSG 1.62g be dissolved in 100ml acetonitrile, add 2.3ml acetic acid, mix and be placed on preheating 15min(40 DEG C in constant temperature oscillator, 200r/min), add 2.00g immobilization Lipozyme TL IM and start reaction, add 100 mg/ml 4 molecular sieves after 24h and continue reaction, judge reaction end with thin layer chromatography.Gained mixture filters, and steams to desolventize to obtain crude product, obtains 6'-through silica gel column chromatography
o-stilbene glucoside acetic ester (1.51g, productive rate is 84.50%).
1H NMR (CD
3OD, 400 MHz): δ = 7.66 (d, 1H,
J=16.4Hz ), 7.37 (d, 2H,
J=8.4Hz), 6.91(d, 1H
J=16.4Hz), 6.82 (d, 2H,
J=8.8 Hz), 6.61(d, 1H,
J=2.8 Hz), 6.24 ( d, 1 H,
J=2.8Hz), 4.48 (d, 1H,
J=7.6 Hz), 4.362-4.327 (m, 1H), 4.249-4.204 (m, 1H), 3.572-3.487 (m, 2H), 3.463-3.369 (m, 2H), 1.854 (s, 3H)。
Embodiment 2
Get purity be 98% TSG 1.62g be dissolved in 100ml acetone, add 3.5ml valeric acid, mix and be placed on preheating 15min(45 DEG C in constant temperature oscillator, 200r/min), add 1.60g Lipase PS IM and start reaction, add 110 mg/ml 4 molecular sieves after 24h and continue reaction, judge reaction end with thin layer chromatography.Mixture filters, and steams to desolventize to obtain crude product, obtains 6'-through silica gel column chromatography
o-stilbene glucoside valerate (1.69g, productive rate is 86.37%).
1H NMR (CD
3OD, 400 MHz): δ = 7.58 (d, 1H,
J=16.4Hz ), 7.44 (d, 2H,
J=8.4Hz), 6.88(d, 1H,
J=16.4Hz), 6.79(d, 2H,
J=8.8 Hz), 6.57(d, 1H,
J=2.8 Hz), 6.22 ( d, 1H,
J=2.8Hz), 4.41(d, 1H,
J=7.6 Hz), 4.38-4.34(m, 1H), 4.26-4.22 (m, 1H), 3.39-3.41(m, 2H), 3.48-3.38 (m, 2H), 2.42-2.29 (m, 2H), 1.83-1.64 (m, 4H), 1.01-0.83 (m, 3H)。
Embodiment 3
Get purity be 98% TSG 1.62g be dissolved in 100ml methylene dichloride, add 8.3ml lauric acid, mix and be placed on preheating 15min(45 DEG C in constant temperature oscillator, 200r/min), add 1.80g novozym 435 and start reaction, add 105 mg/ml 4 molecular sieves after 24h and continue reaction, judge reaction end with thin layer chromatography.Mixture filters, and steams to desolventize to obtain crude product, obtains 6'-through silica gel column chromatography
o-stilbene glucoside laurate (1.94g, productive rate is 82.43%).
1H NMR (CD
3OD, 400 MHz): δ = 7.75 (d, 1H,
J=16.4Hz ), 7.46 (d, 2H,
J=8.4Hz), 7.01(d, 1H
J=16.4Hz), 6.88(d, 2H,
J=8.8 Hz), 6.70(d, 1H,
J=2.8 Hz), 6.33 ( d, 1H,
J=2.8Hz), 4.57 (d, 1H,
J=7.6 Hz), 4.42-4.38 (m, 1H), 4.34-4.29 (m, 1H), 3.61-3.57 (m, 2H), 3.45-3.36(m, 2H), 0.86(s, 3H),1.25-1.13(m, 16H), 2.37-2.26 (m, 2H)。
Embodiment 4
Get purity be 98% TSG 1.63g be dissolved in 100ml acetonitrile, add 3.88g forulic acid, mix and be placed on preheating 15min(40 DEG C in constant temperature oscillator, 200r/min), add 2.16g immobilization Lipase G and start reaction, add 96 mg/ml 4 molecular sieves after 24h and continue reaction, judge reaction end with thin layer chromatography.Gained mixture filters, and steams to desolventize to obtain crude product, obtains producing 6'-through silica gel column chromatography
o-stilbene glucoside ferulic acid ester (2.09g, productive rate is 87.18%).
1H NMR (CD
3OD, 400 MHz): δ = 7.69 (d, 1H,
J=16Hz), 7.61(d, 1H,
J=16Hz), 7.39 (d, 2H,
J=8.4Hz), 7.21-7.19(m, 1H), 7.10(d, 1H,
J=8.1Hz), 6.94(d, 1H
J=16.4Hz), 6.85 (d, 2H,
J=8.8 Hz), 6.80(d, 1H,
J=8.1Hz), 6.67(d, 1H,
J=2.8 Hz), 6.44(d, 1H,
J=16Hz), 6.30( d, 1H,
J=2.8Hz), 4.52 (d, 1H,
J=7.6 Hz), 4.35-4.32 (m, 1H), 4.30-4.264 (m, 1H), 3.97(s, 3H), 3.56-3.50 (m, 2H), 3.47-3.39 (m, 2H)。
Embodiment 5
Get purity be 98% TSG 1.63g be dissolved in 100ml acetonitrile, add 2.7ml vinylformic acid, mix and be placed on preheating 15min(40 DEG C in constant temperature oscillator, 200r/min), add 1.92g immobilization Lipozyme IM and start reaction, add 115mg/ml 4 molecular sieve after 24h and continue reaction, judge reaction end with thin layer chromatography.Gained mixture filters, and steams to desolventize to obtain crude product, obtains 6'-through silica gel column chromatography
o-stilbene glucoside acrylate (1.54g, productive rate is 83.72%).
1H NMR (CD
3OD, 400 MHz): δ = 7.71 (d, 1H,
J=16.4Hz ), 7.42 (d, 2H,
J=8.4Hz), 6.96(d, 1H,
J=16.4Hz), 6.87 (d, 2H,
J=8.8 Hz), 6.66(d, 1H,
J=2.8 Hz),6.42-6.31(m, 1H) , 6.29 ( d, 1H,
J=2.8Hz), 6.15-5.97(m, 1H), 5.83-5.65(m, 1H), 4.53 (d, 1H,
J=7.6Hz), 4.41-4.37 (m, 1H), 4.29-4.25 (m, 1H), 3.63-3.53 (m, 2H), 3.51-3.43 (m, 2H)。
Embodiment 6
Get purity be 98% TSG 1.63g be dissolved in 100ml acetonitrile, add 3.1ml methacrylic acid, mix and be placed on preheating 15min(40 DEG C in constant temperature oscillator, 200r/min), add 2.24g immobilization Lipase PS-D and start reaction, add 90 mg/ml 4 molecular sieves after 24h and continue reaction, judge reaction end with thin layer chromatography.Gained mixture filters, and steams to desolventize to obtain crude product, obtains producing 6'-through silica gel column chromatography
o-stilbene glucoside methacrylic ester (1.63g, productive rate is 85.48%).
1H NMR (CD
3OD, 400 MHz): δ = 7.59 (d, 1H,
J=16.4Hz ), 7.31 (d, 2H,
J=8.4Hz), 6.85(d, 1H,
J=16.4Hz), 6.75 (d, 2H,
J=8.8 Hz), 6.54(d, 1H,
J=2.8 Hz), 6.24(d, 1H,
J=1.7Hz), 6.17(d, 1H,
J=2.8Hz), 5.79(d, 1H,
J=1.7Hz), 4.32 (d, 1H,
J=7.6 Hz), 4.29-4.25 (m, 1H), 4.18-4.13 (m, 1H), 3.51-3.43 (m, 2H), 3.39-3.31 (m, 2H), 1.89(s, 3H)。
Claims (7)
1. the synthetic method of diphenyl ethylene glycosides derivatives shown in structural formula (I), is characterized in that: stilbene glucoside and organic acid RCOOH are obtained by reacting diphenyl ethylene glycosides derivatives shown in structural formula (I) under immobilized lipase exists,
R is the alkyl of C1 ~ C17, the thiazolinyl of C2 ~ C22, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic radical, the alkyl of C1 ~ C17 that hydroxyl, carbonyl, replacement or unsubstituting aromatic yl replace, the thiazolinyl of C2 ~ C22 that hydroxyl, carbonyl, replacement or unsubstituting aromatic yl replace;
The above-mentioned substituting group related to is alkyl, the thiazolinyl of C2 ~ C5, hydroxyl, the alkoxyl group of C1 ~ C5, halogen radical, the carbonyl of C1 ~ C4.
2. the synthetic method of diphenyl ethylene glycosides derivatives according to claim 1, is characterized in that R is following substituting group,
。
3. the synthetic method of diphenyl ethylene glycosides derivatives according to claim 1, is characterized in that: described immobilized lipase is selected from immobilization novozym 435, Lipozyme TL IM, Lipase PS-C, Lipase PS IM, Lipozyme IM, Lipase PS-D, Lipase R, Lipase G, Lipase OF, Lipase A, Lipase M, Lipase PEL.
4. the synthetic method of diphenyl ethylene glycosides derivatives according to claim 3, is characterized in that: the mol ratio of stilbene glucoside and organic acid RCOOH is 1:5-1:12.
5. the synthetic method of diphenyl ethylene glycosides derivatives according to claim 3, it is characterized in that: reaction is carried out in organic solvent, and described organic solvent is selected from THF, MeTHF, acetone, methylene dichloride, benzene, the trimethyl carbinol, toluene, acetonitrile, chloroform, ethyl acetate, N-BUTYL ACETATE.
6. the synthetic method of diphenyl ethylene glycosides derivatives according to claim 3, is characterized in that: temperature of reaction is 40 ~ 55 DEG C.
7. according to the synthetic method of one of any described diphenyl ethylene glycosides derivatives of claim 1 to 6, it is characterized in that: add 4 molecular sieves after having reacted and continue reaction, judge reaction end with thin layer chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410034533.1A CN104805158A (en) | 2014-01-25 | 2014-01-25 | Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410034533.1A CN104805158A (en) | 2014-01-25 | 2014-01-25 | Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104805158A true CN104805158A (en) | 2015-07-29 |
Family
ID=53690355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410034533.1A Pending CN104805158A (en) | 2014-01-25 | 2014-01-25 | Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104805158A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624612A (en) * | 2009-08-07 | 2010-01-13 | 华南理工大学 | Method for catalytic synthesis of glycoside esters compound by immobilized penicillium expansum lipase |
| CN101885723A (en) * | 2010-07-09 | 2010-11-17 | 广西中医学院 | Mangiferin glycolipid derivant and preparation method thereof |
-
2014
- 2014-01-25 CN CN201410034533.1A patent/CN104805158A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624612A (en) * | 2009-08-07 | 2010-01-13 | 华南理工大学 | Method for catalytic synthesis of glycoside esters compound by immobilized penicillium expansum lipase |
| CN101885723A (en) * | 2010-07-09 | 2010-11-17 | 广西中医学院 | Mangiferin glycolipid derivant and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 林君智: "乙二醇葡萄糖苷及其己酸酯的制备与纯化", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
| 毛多斌 等: "葡萄糖及葡萄糖苷的生物催化选择性酯化研究进展", 《日用化学工业》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dückert et al. | Lewis Base Catalyzed [4+ 2] Annulation of Electron‐Deficient Chromone‐Derived Heterodienes and Acetylenes | |
| Zhang et al. | Enantioselective biomimetic cyclization of 2′-hydroxychalcones to flavanones | |
| Patti et al. | Use of Mucor miehei lipase in the preparation of long chain 3-O-acylcatechins | |
| Odani et al. | Total synthesis of pyripyropene A | |
| Kumar et al. | Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant | |
| Liñares et al. | Enzymatic synthesis of bile acid derivatives and biological evaluation against Trypanosoma cruzi | |
| CN109456998B (en) | Method for synthesizing bishydroxycoumarin compound under catalysis of lipase | |
| Bogel-Łukasik et al. | Lipase catalysed mono and di-acylation of secondary alcohols with succinic anhydride in organic media and ionic liquids | |
| Wang et al. | Influence of substituent groups in regioselective acylation of nucleosides by Novozym 435 lipase | |
| Tokairin et al. | Preparation of (2R, 3R, 4R)-3-hydroxy-2, 4, 6-trimethylheptanoic acid via enzymatic desymmertization | |
| CN109705130A (en) | Chromanone skeleton splices polycyclic pyrroles's loop coil Oxoindole compound and preparation method and application | |
| Kim | Prepurification of paclitaxel by micelle and precipitation | |
| Takikawa et al. | Synthesis and absolute configuration of brevione B, an allelochemical isolated from Penicillium sp. | |
| CN104805158A (en) | Method for high-selectivity preparation of stilbene-glucoside derivative through biocatalysis | |
| Singh et al. | Synthetic and novel biocatalytic resolution studies on (±)-5/6/7-acetoxy-4-aryl-3, 4-dihydrocoumarins | |
| JP2012527229A (en) | A chemoenzymatic approach to the synthesis of pimecrolimus. | |
| El-Behairy et al. | One-step lipase-catalysed preparation of eslicarbazepine | |
| Akai et al. | Asymmetric total synthesis of fredericamycin A: An intramolecular cycloaddition pathway | |
| Das et al. | Ti (III)-Mediated Radical-Induced Approach to a Bicyclic δ-Lactone with a Bridgehead β-Hydroxy Group | |
| Baldessari et al. | Lipase‐Catalyzed Acylation and Deacylation Reactions of Pyridoxine, a Member of Vitamin‐B6 Group | |
| Sanfilippo et al. | Convenient access to both enantiomers of new azido-and aminoinositols via a chemoenzymatic route | |
| CN105087707A (en) | Method for catalytically synthesizing dihydromyricetin mono-esterification material by aid of lipase | |
| Park et al. | A novel synthesis of γ-lactones by tandem epoxide opening-cyclization reaction mediated by samarium (II) diiodide | |
| Abbaspour-Gilandeh et al. | The green synthesis of pyrano [3, 2-c] quinoline-2, 5-dione derivatives catalyzed by acidic ionic liquid under ultrasound irradiation | |
| Mukherjee et al. | Enzyme-assisted kinetic resolution of novel 2-naphthol Mannich bases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate 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: 20150729 |