CN105884738B - A kind of method of Microwave-assisted synthesis EGCG aliphatic esters - Google Patents
A kind of method of Microwave-assisted synthesis EGCG aliphatic esters Download PDFInfo
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- CN105884738B CN105884738B CN201510683671.7A CN201510683671A CN105884738B CN 105884738 B CN105884738 B CN 105884738B CN 201510683671 A CN201510683671 A CN 201510683671A CN 105884738 B CN105884738 B CN 105884738B
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
- C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
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Abstract
The invention discloses a kind of method of Microwave-assisted synthesis EGCG aliphatic esters, including Epigallo-catechin gallate (EGCG) and fatty acid chloride 1: 4~6 are dissolved in inert organic solvents in molar ratio；Add in the esterification catalyst of the amount of 2~4 times of Epigallo-catechin gallate (EGCG) substances；Microwave-assisted synthesis is carried out, at a certain temperature, stops reaction after reacting a period of time；It using filter, alkali cleaning, washes, be concentrated under reduced pressure, recrystallize, be then freeze-dried 4~6h and obtain EGCG aliphatic esters.The advantages of method of synthesis EGCG aliphatic esters provided by the present invention utilizes Microwave-assisted synthesis, can achieve the effect that react not available under normal heating conditions, reaction conversion ratio rises to 84.5% by 68% before.
Description
The invention belongs to food additives to synthesize field, is related to a kind of preparation method of improved EGCG aliphatic esters, main
It is related to a kind of method of Microwave-assisted synthesis EGCG aliphatic esters.
Background technology
Catechin is most important physiological activator in tealeaves, accounts for the 60%~80% of tea polyphenols total amount, is tealeaves
The main matter ingredient of healthcare function.With Epigallo-catechin gallate (EGCG) (EGCG) content highest in catechin, account for
50% or so of catechin total amount.Due to anti-oxidant, anti-mutation excellent EGCG, radiation protection, antitumor, adjusting is immune and delays
The physiological activities such as aging, the recent research in relation to EGCG is noticeable, but for its application, there are fat-soluble poor, raw
The problems such as object availability is low, unstable under physiological environment and body absorption is slow.
Based on these problems, make the molecular modification that it is modified by retaining its active group, become EGCG in recent years and grind
One of hot spot studied carefully.It is the weight for changing substance biological activity both at home and abroad at present that conventional heating methods, which carry out molecular structure modification to be,
Want means.But there are shortcomings for the acylation of conventional heating chemical method：Regioselectivity is poor, is also easy to produce substantial amounts of by-product,
Reaction conversion ratio is low, and product yield is low；The shortcomings that reaction rate is slow, and reaction time consumption is long, in actual mechanical process, the reaction time is past
It is past to be up to 12h, but conversion ratio is only 68%, and simultaneous reactions product is monosubstituted, and two substitute, trisubstituted mixture, wherein
Mono-substituted products only account for the 52.8% of reaction product.
The content of the invention
The purpose of this part is to summarize some aspects of the embodiment of the present invention and briefly introduce some preferably to implement
Example.It may do in this section and the description of the application and the title of the invention a little simplified or omit to make our department
Point, the purpose of abstract of description and denomination of invention obscure, and this simplification or omit and cannot be used for limiting the scope of the invention.
In view of problem present in above-mentioned and/or existing synthesis EGCG aliphatic esters, it is proposed that the present invention.
It is therefore an object of the present invention to overcome the shortcoming of existing conventional heating synthesis, provide and a kind of use microwave radiation technology
The method for synthesizing EGCG aliphatic esters synthesizes EGCG aliphatic esters under conditions of microwave radiation technology.
In order to solve the above technical problems, the present invention provides following technical solution：A kind of Microwave-assisted synthesis EGCG aliphatic acid
The method of ester, including, by Epigallo-catechin gallate (EGCG) and fatty acid chloride in molar ratio 1: 4~6 be dissolved in it is lazy
In property organic solvent；Add in the esterification catalyst of the amount of 2~4 times of Epigallo-catechin gallate (EGCG) substances；Carry out microwave
Auxiliary synthesis at a certain temperature, stops reaction after reacting a period of time；Using filter, alkali cleaning, wash, be concentrated under reduced pressure, tie again
Then crystalline substance is freeze-dried 4~6h and obtains EGCG aliphatic esters.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
Inertia organic reagent is stated as one kind in ethyl acetate or tetrahydrofuran or n,N-Dimethylformamide, and its volume is not eaten for table
100~120: the 1 of sub- catechin and gallate and fatty acid chloride quality.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
Esterification catalyst is stated to be esterified for sodium acid carbonate and/or saleratus.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
Stating fatty acid chloride is one kind in the fatty acid chloride containing 12~18 carbon atoms or any number of is mixed with arbitrary proportion.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
The frequency for stating microwave reaction is 2400~2500MHz.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
Certain temperature is stated as 40~60 DEG C.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
It is 1.5~2.5h to state reaction a period of time.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
It is to be removed palmitic acid excessive in reaction solution using saturated sodium bicarbonate solution to state alkali cleaning.
A kind of preferred embodiment of method as Microwave-assisted synthesis EGCG aliphatic esters of the present invention, wherein：Institute
It is that the EGCG aliphatic esters that will be recrystallized to give are placed in freeze drier to state freeze-drying, at subzero 40 DEG C, vacuum degree
Under the conditions of 0.01mbar, dry 6h.
Beneficial effects of the present invention：The method of synthesis EGCG aliphatic esters provided by the present invention utilizes Microwave-assisted synthesis
The advantages of, it can achieve the effect that react not available under normal heating conditions, reaction conversion ratio is risen to by 68% before
84.5%, the reaction time foreshortens to 2h, also without the presence of trisubstitution product, monosubstituted EGCG aliphatic acid in simultaneous reactions product
The ratio of ester is also improved to 86.6%.It can be seen that Microwave-assisted synthesis can substantially accelerate reaction speed, reaction conversion is improved
Rate.So as to provide a kind of synthetic method that is efficient, quick, meeting Green Chemistry.
Description of the drawings
Fig. 1 is EGCG palmitoylation product mass spectra analysis charts in embodiment 1；In figure, signal peak 457 divides for unreacted EGCG
Daughter ion peak, the anion fragment peak that karyoplasmic ratio is 169 is the galloyl in EGCG structures, due to the molecule of palmityl
It measures as 239, therefore often substitutes a palmityl in EGCG molecules, molecular weight will increase by 138, so karyoplasmic ratio is in figure
695 peak is the one substitution product quasi-molecular ions of palmityl of EGCG, and the peak that karyoplasmic ratio is 933 is that the palmityl two of EGCG substitutes
Product ion peak.
Fig. 2 is the liquid chromatogram for implementing EGCG palmitoylation products in 1, wherein peak 1, and peak 2 is monosubstituted for main EGCG
Product accounts for the 86.6% of reaction product.
Fig. 3 is the liquid chromatogram of EGCG palmitoylation products in comparison example 1, wherein peak 1, and peak 2 is mono- for main EGCG
Substitution product accounts for the 52.8% of reaction product.
Specific embodiment
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, with reference to Figure of description pair
The specific embodiment of the present invention is described in detail.
Many details are elaborated in the following description to facilitate a thorough understanding of the present invention, still the present invention can be with
Implemented using other different from other manner described here, those skilled in the art can be without prejudice to intension of the present invention
In the case of do similar popularization, therefore the present invention is from the limitation of following public specific embodiment.
Secondly, " one embodiment " or " embodiment " referred to herein refers to may be included at least one realization side of the present invention
A particular feature, structure, or characteristic in formula." in one embodiment " that different places occur in the present specification not refers both to
Same embodiment, nor the individual or selective embodiment mutually exclusive with other embodiment.
Embodiment 1：
2.2g EGCG are dissolved in 60mL ethyl acetate to be placed in 100mL three-necked flasks, add 4.6g sodium acid carbonates,
Three-necked flask is placed in microwave reactor, starts microwave reactor, 60 DEG C of reaction temperature is set, is delayed by constant pressure funnel
It is slow that 6.8g palmitoyl chlorides are added dropwise, 2h is reacted, reaction solution is filtered, alkali cleaning, washes, is concentrated under reduced pressure, recrystallizing, and dry 6h is obtained
The faint yellow EGCG palmitates of 2.84g, the rate of recovery 78.6%.Conversion ratio through efficient liquid phase chromatographic analysis EGCG is
85.2%, wherein monosubstituted EGCG palmitates account for the 86.6% of reaction product.
The analysis of EGCG palmitoylations product mass spectra is as shown in Figure 1.
Signal peak 457 is unreacted EGCG molecular ion peaks in figure, and the anion fragment peak that karyoplasmic ratio is 169 is EGCG knots
Galloyl in structure.Since the molecular weight of palmityl is often substitutes a palmityl in 239, EGCG molecules,
Molecular weight will increase by 138, thus in figure karyoplasmic ratio be 695 peak be EGCG one substitution product quasi-molecular ions of palmityl, matter
Core than be for 933 peak EGCG two substitution product quasi-molecular ions of palmityl.
Fig. 2 is the liquid chromatogram of EGCG palmitoylations product in embodiment 1, wherein peak 1, and peak 2 takes for main EGCG is mono-
For product, the 86.6% of reaction product is accounted for.
Comparison example 1
2.2g EGCG are dissolved in 60mL ethyl acetate to be placed in 100mL three-necked flasks, add 4.6g sodium acid carbonates,
Three-necked flask is placed in 60 DEG C of thermostat water baths, 6.8g palms are slowly added dropwise by constant pressure funnel in water bath with thermostatic control heating
Acyl chlorides, react 2h, stop reaction after, reaction solution is filtered, alkali cleaning, wash, be concentrated under reduced pressure, recrystallize dry 6h, obtain
The faint yellow EGCG palmitates of 0.96g, the rate of recovery 32.8%.Conversion ratio through efficient liquid phase chromatographic analysis EGCG is
18.6%, wherein monosubstituted EGCG palmitates account for the 52.8% of reaction product.
Fig. 3 is the liquid chromatogram of EGCG palmitoylations product in comparison example 1, wherein peak 1, and peak 2 is mono- for main EGCG
Substitution product accounts for the 52.8% of reaction product.
Embodiment 2：
4.6g EGCG are dissolved in 120mL tetrahydrofurans to be placed in 250mL three-necked flasks, add 10.2g sodium carbonate,
Three-necked flask is placed in microwave reactor, starts microwave reactor, 60 DEG C of reaction temperature is set, is delayed by constant pressure funnel
It is slow that 15.6g stearyl chlorides are added dropwise, 2.5h is reacted, after stopping reaction, reaction solution is filtered, alkali cleaning, washes, is concentrated under reduced pressure, tying again
Then crystalline substance is freeze-dried 5h, obtain the faint yellow EGCG stearates of 5.69g, the rate of recovery 76.3%.Through high performance liquid chromatography point
The conversion ratio for analysing EGCG is 83.6%.
Embodiment 3
1.2gEGCG is dissolved in 40mL n,N-dimethylacetamide to be placed in 100mL three-necked flasks, adds 2.64g
Three-necked flask is placed in microwave reactor by triethylamine, starts microwave reactor, is set 50 DEG C of reaction temperature, is dripped by constant pressure
Liquid funnel is slowly added dropwise 3.12g bay isoxazolecarboxylic acids, reacts 2h, and after stopping reaction, reaction solution is filtered, alkali cleaning, washing, decompression are dense
Contracting, recrystallization, are then freeze-dried 6h, obtain the faint yellow EGCG laurates of 1.45g, the rate of recovery 78.8%.Through efficient liquid
The conversion ratio of analysis of hplc EGCG is 86.4%.
Embodiment 4
2.3g EGCG are dissolved in 60mL n,N-dimethylacetamide to be placed in 100mL three-necked flasks, add 4.45g
Three-necked flask is placed in microwave reactor by pyridine, starts microwave reactor, is set 60 DEG C of reaction temperature, is passed through constant pressure addition
Funnel is slowly added dropwise 7.4g palmitoyl chlorides, reacts 2.5h, after stopping reaction, reaction solution is filtered, alkali cleaning, wash, be concentrated under reduced pressure,
Recrystallization, is then freeze-dried 6h, obtains the faint yellow EGCG palmitates of 2.76g, the rate of recovery 76.2%.Through high-efficient liquid phase color
The conversion ratio of spectrum analysis EGCG is 84.1%.
It can be seen that the advantages of method of synthesis EGCG aliphatic esters provided by the present invention utilizes Microwave-assisted synthesis,
It can achieve the effect that react not available under normal heating conditions.Microwave radiation can be such that reaction system is uniformly made be subject to microwave field
With system heating rate is fast, and temperature is uniformly and holding is stablized, and can substantially accelerate reaction speed, improve reaction yield, improve reaction
Conversion ratio.So as to provide a kind of synthetic method that is efficient, quick, meeting Green Chemistry.
It should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to preferable
The present invention is described in detail in embodiment, it will be understood by those of ordinary skill in the art that, it can be to the technology of the present invention
Scheme is modified or replaced equivalently, and without departing from the spirit and scope of technical solution of the present invention, should all be covered in this hair
Among bright right.
Claims (1)
- A kind of 1. method of Microwave-assisted synthesis EGCG aliphatic esters, it is characterised in that：2.2g EGCG are dissolved in 60mL acetic acid Ethyl ester is placed in 100mL three-necked flasks, adds 4.6g sodium acid carbonates, three-necked flask is placed in microwave reactor, is started micro- Ripple reactor sets 60 DEG C of reaction temperature, and 6.8g palmitoyl chlorides are slowly added dropwise by constant pressure funnel, react 2h, reaction solution Filtered, alkali cleaning is washed, is concentrated under reduced pressure, recrystallizing, and dry 6h obtains the faint yellow EGCG palmitates of 2.84g, the rate of recovery is 78.6%, the conversion ratio through efficient liquid phase chromatographic analysis EGCG is 85.2%, wherein monosubstituted EGCG palmitates account for reaction production The 86.6% of object.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1448395A (en) * | 2003-04-03 | 2003-10-15 | 浙江大学 | Antioxidant EGCG aliphatic ester and prep. thereof |
| CN101519395A (en) * | 2008-10-16 | 2009-09-02 | 中国农业科学院茶叶研究所 | Preparation method of fully substituted acetylate of epigallocatechin-gallate (EGCG) |
| CN102382094A (en) * | 2011-11-13 | 2012-03-21 | 宜昌绿源生物技术有限公司 | Preparation method of acetylated epigallocatechin gallate |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1448395A (en) * | 2003-04-03 | 2003-10-15 | 浙江大学 | Antioxidant EGCG aliphatic ester and prep. thereof |
| CN101519395A (en) * | 2008-10-16 | 2009-09-02 | 中国农业科学院茶叶研究所 | Preparation method of fully substituted acetylate of epigallocatechin-gallate (EGCG) |
| CN102382094A (en) * | 2011-11-13 | 2012-03-21 | 宜昌绿源生物技术有限公司 | Preparation method of acetylated epigallocatechin gallate |
Non-Patent Citations (1)
| Title |
|---|
| Enhanced anti-influenza A virus activity of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives:Effect of alkyl chain length;Shuichi Mori et al.;《Bioorganic & Medicinal Chemistry Letters》;20080210;第18卷;4249-4252 * |
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Address after: 214000 Liangxi District Food Park, 7th floor, South Building, No. 898, Tongsha Road, Liangxi District, Wuxi City, Jiangsu Province Patentee after: Jiangnan University Address before: No. 1800 road 214000 Jiangsu Lihu Binhu District City of Wuxi Province Patentee before: Jiangnan University |