CN109593092A - A method of ellagic acid is synthesized using gallic acid-derivate - Google Patents
A method of ellagic acid is synthesized using gallic acid-derivate Download PDFInfo
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- CN109593092A CN109593092A CN201910103504.9A CN201910103504A CN109593092A CN 109593092 A CN109593092 A CN 109593092A CN 201910103504 A CN201910103504 A CN 201910103504A CN 109593092 A CN109593092 A CN 109593092A
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- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
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Abstract
The invention discloses a kind of method using gallic acid-derivate synthesis ellagic acid, technology path is: utilizing gallic acid-derivate and 10~25%NH3.H2O ammonification 5~for 24 hours in 45~55 DEG C of water-baths, then oxidant is added to ammoniated solution and carries out oxidation reaction 5~for 24 hours, after reaction, reaction solution is filtered, filter cake NaOH aqueous dissolution.Alkaline solution is extracted with organic solvent, then adjusts water phase pH to 1.0~2.5, crystallization, filtering with HCl solution, and vacuum drying obtains light yellow ellagic acid.This method raw material is cheap, and reaction temperature is mild, reaction process safety, easily controllable；The reported yield of productivity ratio wants high, can reach 70% or more；The method synthesis ellagic acid, color be it is light yellow, purity can reach 98% or more.
Description
Technical field
The present invention relates to a kind of preparation method using gallic acid-derivate synthesis ellagic acid, this method preparation process peaces
It is complete reliable, operating process is simple, yield is high, and the color of product is good.
Background technique
Ellagic acid (Ellagicacid, chemical name: 2,3,7,8- tetrahydroxys-[1]-chromene simultaneously [5,4,3-cde] benzene
And pyrans -5,10- diketone, English name are as follows: 2,3,7,8-tetrahydroxy-benzo-pyrano [5,4,3-cde]
Benzopyran-5,10-dione).It is a kind of light yellow in amorphous powder, not soluble in water, ether, alcohol, be but dissolved in alkali,
Pyridine, DMSO, fusing point are greater than 360 DEG C.Ellagic acid is a kind of polyphenol compound, in nature with condensed forms (such as tan
Flower tannin) exist, with FeCl3It reacts blue, meets H2SO4In yellow.It is widely present in the plants group such as various mushy fruits, nut
In knitting, such as tropical fruit (tree), raspberry, pomegranate, strawberry, walnut fruit, it is two polyacene derivatives of Gallic Acid
Object is in trans- gallic acid tannin structure.Its molecular formula is C14H6O8, structure is as follows.
As scientific circles are to the continuous research of ellagic acid and report, discovery ellagic acid has to the canceration that chemical substance induces
Apparent inhibiting effect especially has colon cancer, the cancer of the esophagus, liver cancer, lung cancer, tongue and skin neoplasin etc. and inhibits to make well
With；Human body immunodeficiency virus (HIV), in terms of have good activity；To various bacteria, fungi, ferment
In female bacterium inhibiting effect；It is preventing from infecting, in terms of inhibiting ulcer and reducing blood lipid, hypoglycemic, calm aspect also have good effect；
Because natural ellagic acid can inhibit cancer cell DNAG1Expression, makes apoptosis in cancer cells, promotes the mitosis of normal cell
On the other hand two-way to repair sieve P53 gene, i.e. control P53 Mutagenesis and mutation, and the P53 gene of mutagenesis and mutation is modified,
" unique natural kind that ellagic acid is last decade anticancer product " alleged by the Brookings cancer research in the U.S..
The preparation method report of ellagic acid is relatively more, mainly there is chemical synthesis, biosynthesis and plant extract etc..1956
Year, Jurd etc. reports [Jurd.J.Am.Chem.Soc, 1956,78,3445-3448], using ellagic acid flower tannin as raw material, in height
Under the conditions of temperature, sulphuric acid hydrolysis, the yield for preparing ellagic acid can reach 40%.But this preparation route is in high temperature, strong acid effect
Under, high, condition requirement harshness, high production cost are required industrial equipment, therefore are difficult to industrialize；1984, the report such as Mayer
[Mayer.LiebigsAnn.Chem, 1984,929-938], using gallic acid as raw material, using peroxidase, oxidation is not eaten
Sub- acid prepares ellagic acid, and by-product is more, and yield only has 20-30%, post-processes more troublesome, it is difficult to purify；2010, the residence of a high official
Young army etc. reports [DiY.J., JiaG.F., Prog.Mad.Biomed., 2010,10:3703-3705], using ultrasonic extraction and
Then acid-hydrolysis method extracts natural ellagic acid using pomegranate peel residue as raw material from pomegranate powder.Dilute hydrochloric acid and pomegranate are used again
Skin, the suspension being configured to, suspension ultrasonic extraction twice, ellagic acid recovery rate is up to 4.3%；2010, Lu Jing
Crystalline substance etc. reports [LuJ.J., etal.FoodSci., 2010,21:451-454], using Ellagitannins as raw material, in acid, fire-bar
Under part, ellagic acid is used to prepare through reflux, collecting processes.This method prepares the yield of ellagic acid 40% or so, but reacts
Condition requires harsh, acid-resistant system requirement height, and high production cost, therefore is difficult to realize industrialization；2013, the report such as Yang Xiaoxiao
[YangX.X., etal.Sci.Technol.Food, 2013,34:284-288], ellagic acid, the party are prepared using Hydrolyze method
Method is mainly raw material to Pomegranate Rind, is extracted with 60% EtOH Sonicate, extracting solution removes fat-soluble through petroleum ether extraction
It after substance, then extracts through ethyl acetate, obtained extract liquor is hydrolyzed with acid-hydrolysis method, obtains ellagic acid, and this method prepares tan flower
Acid is up to 32.7%.
The yield that ellagic acid preparation has been reported is lower, causes its price per ton at ten thousand yuan of 20-30 or so.Develop yield
Height, and it is the research hotspot for commercially producing concern that the simple ellagic acid preparation method of synthesis technology is appointed so so far.
Summary of the invention
The present invention is a kind of method of gallic acid-derivate synthesis ellagic acid.Using the gallic acid-derivate being easy to get,
By ammonification, oxidation one kettle way, synthesis obtains ellagic acid.The synthetic route can obtain the ellagic acid of high-purity, entire to synthesize
Process is easy to operate, and securely and reliably, yield can achieve 70% or more.
Technical scheme is as follows: a method of ellagic acid being synthesized using gallic acid-derivate, reaction is closed
It is as follows at technology path:
Wherein, R H, CH3、CH2CH3、(CH2)2CH3、(CH2)3CH3、(CH2)4CH3、(CH2)5CH3、(CH2)6CH3、
(CH2)7CH3、(CH2)8CH3Or (CH2)9CH3；Oxidant is air, O2、O3、Cl2、m-CPBA、H2O2、OXONE、K2S2O8Or
MnO2。
After reaction, reaction solution is filtered, filter cake is dissolved with NaOH solution, be added under active carbon mild heat and take off
Color, filtering, filtrate extracts with organic solvent, and water intaking mutually adjusts extract liquor pH with hydrochloric acid, crystallization, filtering, dry light yellow tan
Spend sour ambiguity powder.
The gallic acid-derivate and ammonia volume ratio is 1: 50, and unit is grams per milliliter, and wherein ammonia concn is 10
~25%, reaction temperature is 45~55 DEG C.
Using gas as oxidant, reaction system is introduced gas into, the time that gas imports is 12~for 24 hours；It is tried with solid
Agent is oxidant, and reaction system is added in the oxidant of 1~2 equivalent.The concentration of the NaOH aqueous solution is 5%~50%.Institute
The activated carbon dosage and gallic acid-derivate ratio stated are 1: 5, and heating temperature is 25~45 DEG C.The organic solvent is dichloro
Methane, chloroform or ethyl acetate.The concentration of the hydrochloric acid is 5%~25%.The adjusting filtrate pH is 1.0~2.5.
The present invention is to synthesize ellagic acid using gallic acid-derivate, and the spy of ellagic acid is obtained under the conditions of the technology path
Point compared with prior art, has the advantage that
1. raw material is cheap, reaction temperature is mild, reaction process safety, easily controllable.
2. the reported yield of productivity ratio of technology path synthesis ellagic acid wants high, 70% or more can reach.
3. the method synthesis ellagic acid, color be it is light yellow, purity can reach 98% or more.
Embodiment
Embodiment 1
Gallicin 50g is weighed, is poured into after drying in 500ml three-necked flask, 25% concentrated ammonia liquor is then added
250ml clogs bottleneck with bottle stopper, is put into 50 DEG C of thermostat water baths, stirs 12h, reaction solution is then poured into 1000ml and is done
In dry three-necked flask, air is imported, oxidation reaction is for 24 hours.After reaction, reaction solution is filtered, filter cake is molten with 25%NaOH
Liquid dissolution, puts into active carbon 250g, decoloration is stirred at 25 DEG C, filters, and filtrate is extracted with dichloromethane three times, separation filter
Liquid, it is 2 that 25% hydrochloric acid of water phase, which adjusts extract liquor pH, crystallization, filtering, dry light yellow ellagic acid indefinite form powder, yield
It is 72%.
Embodiment 2
Progallin A 50g is weighed, is poured into after drying in 500ml three-necked flask, 25% concentrated ammonia liquor is then added
250ml clogs bottleneck with bottle stopper, is put into 50 DEG C of thermostat water baths and stirs 12h, and it is dry that reaction solution is then poured into 1000ml
In three-necked flask, potassium peroxydisulfate 100g is put into, reacts 5h.After reaction, reaction solution is filtered, filter cake is molten with 15%NaOH
Liquid dissolution, puts into active carbon 250g, and in 30 DEG C of progress decolorizing and refinings, filtering, filtrate is extracted with ethyl acetate three times, separation filter
Liquid, it is 1.5 that 15% hydrochloric acid of water phase, which adjusts extract liquor pH, and crystallization, filtering, dry light yellow ellagic acid indefinite form powder produce
Rate is 81%.
Embodiment 3
Propylgallate 50g is weighed, is poured into after drying in 500ml wide-mouth bottle, 25% concentrated ammonia liquor 250ml is then added,
Bottleneck is clogged with bottle stopper, is put into 50 DEG C of thermostat water baths and stirs 12h, reaction solution is then poured into the dry three mouthfuls of burnings of 1000ml
In bottle, m-CPBA60g is put into, reacts 10h.After reaction, reaction solution is filtered, filter cake 10%NaOH solution is dissolved,
Active carbon 250g is put into, decolourizes, filters in 35 DEG C of stirrings, filtrate is extracted with dichloromethane three times, separating filtrate, and filtrate is with 10%
It is 2 that hydrochloric acid, which adjusts extract liquor pH, crystallization, filtering, dry light yellow ellagic acid.Its yield is 84%.
Claims (9)
1. a kind of method using gallic acid-derivate synthesis ellagic acid, it is characterised in that: its reactive synthesis technique route is such as
Under:
Wherein, R H, CH3、CH2CH3、(CH2)2CH3、(CH2)3CH3、(CH2)4CH3、(CH2)5CH3、(CH2)6CH3、(CH2)7CH3、(CH2)8CH3Or (CH2)9CH3；Oxidant is air, O2、O3、Cl2、m-CPBA、H2O2、OXONE、K2S2O8Or MnO2。
2. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 1, it is characterised in that: anti-
After answering, reaction solution is filtered, filter cake is dissolved with NaOH solution, is added under active carbon mild heat and decolourizes, is filtered, filtrate
It is extracted with organic solvent, water intaking mutually adjusts extract liquor pH, crystallization, filtering, dry light yellow ellagic acid ambiguity powder with hydrochloric acid
End.
3. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 1, it is characterised in that: institute
The gallic acid-derivate and ammonia volume ratio stated are 1: 50, and unit is grams per milliliter, and wherein ammonia concn is 10-25%, reaction
Temperature is 45-55 DEG C.
4. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 1, it is characterised in that: with
Gas introduces gas into reaction system as oxidant, and the time that gas imports is 12-24h；Using solid reagent as oxidant,
Reaction system is added in the oxidant of 1-2 equivalent.
5. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 2, it is characterised in that: institute
The concentration for stating NaOH aqueous solution is 5%-50%.
6. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 2, it is characterised in that: institute
The activated carbon dosage and gallic acid-derivate ratio stated are 1: 5, and heating temperature is 25-45 DEG C.
7. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 2, it is characterised in that: institute
The organic solvent stated is methylene chloride, chloroform or ethyl acetate.
8. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 2, it is characterised in that: institute
The concentration for stating hydrochloric acid is 5%-25%.
9. a kind of method using gallic acid-derivate synthesis ellagic acid according to claim 2, it is characterised in that: institute
Stating and adjusting filtrate pH is 1.0-2.5.
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| CN201810398424.6A CN108395440A (en) | 2018-04-28 | 2018-04-28 | A method of synthesizing ellagic acid using gallic acid-derivate |
| CN2018103984246 | 2018-04-28 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128437A (en) * | 2019-05-22 | 2019-08-16 | 中科萱嘉医养(珠海)健康科技有限公司 | A kind of high-purity ellagic acid and the preparation method and application thereof |
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|---|---|---|---|---|
| CN110066284B (en) * | 2019-02-01 | 2021-06-04 | 贵阳倍隆生物科技有限公司 | Method for synthesizing ellagic acid by one-pot method |
| CN116370406B (en) * | 2023-06-02 | 2023-08-15 | 云南伦扬科技有限公司 | Nanometer enzyme injectable hydrogel for treating hemorrhoids |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004155666A (en) * | 2002-11-01 | 2004-06-03 | Mitsubishi Chemicals Corp | Method for producing ellagic acid |
| CN105524074A (en) * | 2016-02-02 | 2016-04-27 | 中国林业科学研究院林产化学工业研究所 | Method for preparing ellagic acid through basic hydrolysis of tannin in Platycarya strobilacea fruits |
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Patent Citations (2)
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|---|---|---|---|---|
| JP2004155666A (en) * | 2002-11-01 | 2004-06-03 | Mitsubishi Chemicals Corp | Method for producing ellagic acid |
| CN105524074A (en) * | 2016-02-02 | 2016-04-27 | 中国林业科学研究院林产化学工业研究所 | Method for preparing ellagic acid through basic hydrolysis of tannin in Platycarya strobilacea fruits |
Non-Patent Citations (3)
| Title |
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| J. HERZIG ET AL.: "Zur Konstitution der Ellagsaure", 《 MONATSHEFTE FUR CHEMIE》 * |
| 冯兵: "鞣花酸的合成及含量测定方法研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
| 南京林产工业学院: "《栲胶生产工艺学》", 31 December 1983, 中国林业出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110128437A (en) * | 2019-05-22 | 2019-08-16 | 中科萱嘉医养(珠海)健康科技有限公司 | A kind of high-purity ellagic acid and the preparation method and application thereof |
| CN110128437B (en) * | 2019-05-22 | 2020-11-24 | 韶关市嘉德绿色工艺与材料研究院 | High-purity ellagic acid and preparation method and application thereof |
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