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
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- egcg
- microwave
- reaction
- fatty acid
- assisted synthesis
- 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.)
- Active
Links
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 title claims abstract description 70
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000007144 microwave assisted synthesis reaction Methods 0.000 title claims abstract description 18
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- -1 EGCG fatty acid ester Chemical class 0.000 claims abstract description 32
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 28
- 239000000194 fatty acid Substances 0.000 claims abstract description 28
- 229930195729 fatty acid Natural products 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000007795 chemical reaction product Substances 0.000 claims description 10
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims description 4
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- 229940030275 epigallocatechin gallate Drugs 0.000 abstract description 62
- 208000012839 conversion disease Diseases 0.000 abstract description 5
- 238000010438 heat treatment Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 230000032050 esterification Effects 0.000 abstract description 4
- 238000005886 esterification reaction Methods 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000012141 concentrate Substances 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 17
- 230000026792 palmitoylation Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 241001122767 Theaceae Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 3
- 235000005487 catechin Nutrition 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000001450 anions Chemical group 0.000 description 2
- 150000001765 catechin Chemical class 0.000 description 2
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical compound CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000002019 anti-mutation Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种微波辅助合成EGCG脂肪酸酯的方法，其包括，将表没食子儿茶素没食子酸酯和脂肪酸酰氯按摩尔比1∶4～6溶解于惰性有机溶剂中；加入2～4倍表没食子儿茶素没食子酸酯物质的量的酯化催化剂；进行微波辅助合成，在一定温度下，反应一段时间后停止反应；再经过滤、碱洗、水洗、减压浓缩、重结晶，然后冷冻干燥4～6h得到EGCG脂肪酸酯。本发明所提供的合成EGCG脂肪酸酯的方法利用微波辅助合成的优点，能达到常规加热条件下反应所不具备的效果，反应转化率由之前的68％提高为84.5％。
The invention discloses a microwave-assisted method for synthesizing EGCG fatty acid ester, which comprises: dissolving epigallocatechin gallate and fatty acid acid chloride in an inert organic solvent in a molar ratio of 1:4-6; adding 2-4 Esterification catalyst times the amount of epigallocatechin gallate; carry out microwave-assisted synthesis, at a certain temperature, stop the reaction after reacting for a period of time; then filter, wash with alkali, wash with water, concentrate under reduced pressure, and recrystallize. Then freeze-dry for 4-6 hours to obtain EGCG fatty acid ester. The method for synthesizing EGCG fatty acid ester provided by the present invention utilizes the advantage of microwave-assisted synthesis, and can achieve the effect that the reaction under conventional heating conditions does not have, and the reaction conversion rate is increased from 68% to 84.5%.
Description
本发明属于食品添加剂合成领域，涉及一种改进的EGCG脂肪酸酯的制备方法，主要涉及一种微波辅助合成EGCG脂肪酸酯的方法。The invention belongs to the field of food additive synthesis, relates to an improved preparation method of EGCG fatty acid ester, and mainly relates to a microwave-assisted synthesis method of EGCG fatty acid ester.
背景技术Background technique
儿茶素是茶叶中最重要的生理活性物质，约占茶多酚总量的60％～80％，是茶叶保健功能的主要物质成分。儿茶素中以表没食子儿茶素没食子酸酯(EGCG)含量最高，约占儿茶素总量的50％左右。由于EGCG优异的抗氧化、抗突变、防辐射、抗肿瘤、调节免疫和延缓衰老等生理活性作用，近来有关EGCG的研究引人瞩目，但就其应用而言，存在脂溶性差、生物利用度低、生理环境下不稳定和体内吸收缓慢等问题。Catechin is the most important physiologically active substance in tea, accounting for about 60% to 80% of the total amount of tea polyphenols, and is the main material component of tea's health care function. Among the catechins, epigallocatechin gallate (EGCG) has the highest content, accounting for about 50% of the total catechins. Due to EGCG's excellent physiological activities such as anti-oxidation, anti-mutation, radiation protection, anti-tumor, immune regulation and anti-aging, recent researches on EGCG have attracted attention, but in terms of its application, there are poor fat solubility and bioavailability Low, unstable in physiological environment and slow absorption in the body.
基于这些问题，通过保留其活性基团而使其改性的分子修饰，成为近年来EGCG研究的热点之一。常规加热方法进行分子结构改性是目前国内外是改变物质生物学活性的重要手段。但是常规加热化学方法酰化存在诸多缺点：区域选择性差，易产生大量的副产物，反应转化率低，产物收率低；反应速率慢，反应耗时长的缺点，实际操作过程中，反应时间往往长达12h，但转化率仅仅为68％，同时反应产物是单取代，二取代，三取代的混合物，其中单取代产物仅占反应产物的52.8％。Based on these problems, molecular modification by retaining its active groups has become one of the hotspots of EGCG research in recent years. Modification of molecular structure by conventional heating method is an important means to change the biological activity of substances at home and abroad. However, there are many disadvantages in the acylation of the conventional thermal chemical method: poor regioselectivity, easy to produce a large amount of by-products, low reaction conversion rate, and low product yield; slow reaction rate and long reaction time. In the actual operation process, the reaction time is often Up to 12h, but the conversion rate is only 68%, and the reaction product is a mixture of mono-substitution, di-substitution and tri-substitution, and the mono-substitution product only accounts for 52.8% of the reaction product.
发明内容Contents of the invention
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。The purpose of this section is to outline some aspects of embodiments of the invention and briefly describe some preferred embodiments. Some simplifications or omissions may be made in this section, as well as in the abstract and titles of this application, to avoid obscuring the purpose of this section, the abstract and titles, and such simplifications or omissions should not be used to limit the scope of the invention.
鉴于上述和/或现有合成EGCG脂肪酸酯中存在的问题，提出了本发明。In view of the above and/or problems existing in the existing synthesis of EGCG fatty acid esters, the present invention is proposed.
因此，本发明的目的是克服现有常规加热合成的不足之处，提供一种用微波辅助合成EGCG脂肪酸酯的方法，在微波辅助的条件下合成EGCG脂肪酸酯。Therefore, the purpose of the present invention is to overcome the deficiencies of existing conventional heating synthesis, to provide a method for the synthesis of EGCG fatty acid esters assisted by microwaves, and to synthesize EGCG fatty acid esters under microwave-assisted conditions.
为解决上述技术问题，本发明提供如下技术方案：一种微波辅助合成EGCG脂肪酸酯的方法，其包括，将表没食子儿茶素没食子酸酯和脂肪酸酰氯按摩尔比1∶4～6溶解于惰性有机溶剂中；加入2～4倍表没食子儿茶素没食子酸酯物质的量的酯化催化剂；进行微波辅助合成，在一定温度下，反应一段时间后停止反应；再经过滤、碱洗、水洗、减压浓缩、重结晶，然后冷冻干燥4～6h得到EGCG脂肪酸酯。In order to solve the above-mentioned technical problems, the present invention provides the following technical scheme: a method for microwave-assisted synthesis of EGCG fatty acid esters, which includes dissolving epigallocatechin gallate and fatty acid acyl chloride in a molar ratio of 1: 4 to 6 In an inert organic solvent; add an esterification catalyst of 2 to 4 times the amount of epigallocatechin gallate; carry out microwave-assisted synthesis, and stop the reaction after a period of reaction at a certain temperature; then filter, alkali wash, Wash with water, concentrate under reduced pressure, recrystallize, and freeze-dry for 4-6 hours to obtain EGCG fatty acid ester.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述惰性有机试剂为乙酸乙酯或四氢呋喃或N，N-二甲基甲酰胺中的一种，且其体积为表没食子儿茶素没食子酸酯和脂肪酸酰氯质量的100～120∶1。As a preferred version of the method for the microwave-assisted synthesis of EGCG fatty acid esters of the present invention, wherein: the inert organic reagent is one of ethyl acetate or tetrahydrofuran or N,N-dimethylformamide, and Its volume is 100-120:1 of the mass of epigallocatechin gallate and fatty acid chloride.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述酯化催化剂为碳酸氢钠和/或碳酸氢钾酯化。As a preferred version of the method for microwave-assisted synthesis of EGCG fatty acid esters described in the present invention, wherein: the esterification catalyst is sodium bicarbonate and/or potassium bicarbonate esterification.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述脂肪酸酰氯是含有12～18个碳原子的脂肪酸酰氯中的一种或任意种以任意比例混合。As a preferred version of the method for microwave-assisted synthesis of EGCG fatty acid esters in the present invention, wherein: the fatty acid chlorides are one or any of the fatty acid chlorides containing 12 to 18 carbon atoms mixed in any proportion.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述微波反应的频率为2400～2500MHz。As a preferred solution of the method for microwave-assisted synthesis of EGCG fatty acid ester described in the present invention, wherein: the frequency of the microwave reaction is 2400-2500 MHz.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述一定温度为40～60℃。As a preferred solution of the method for microwave-assisted synthesis of EGCG fatty acid ester in the present invention, wherein: the certain temperature is 40-60°C.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述反应一段时间为1.5～2.5h。As a preferred scheme of the method for microwave-assisted synthesis of EGCG fatty acid ester in the present invention, wherein: the reaction period is 1.5-2.5 hours.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述碱洗是采用饱和碳酸氢钠溶液将反应液中过量的棕榈酸除去。As a preferred version of the method for the microwave-assisted synthesis of EGCG fatty acid esters in the present invention, wherein: the alkali washing is to use saturated sodium bicarbonate solution to remove excess palmitic acid in the reaction solution.
作为本发明所述的微波辅助合成EGCG脂肪酸酯的方法的一种优选方案，其中：所述冷冻干燥是将重结晶得到的EGCG脂肪酸酯置于冷冻干燥机中，在零下40℃，真空度0.01mbar条件下，干燥6h。As a preferred version of the method for the microwave-assisted synthesis of EGCG fatty acid esters of the present invention, wherein: the freeze-drying is to place the EGCG fatty acid esters obtained by recrystallization in a freeze dryer at minus 40°C under vacuum Under the condition of 0.01mbar, dry for 6h.
本发明的有益效果：本发明所提供的合成EGCG脂肪酸酯的方法利用微波辅助合成的优点，能达到常规加热条件下反应所不具备的效果，反应转化率由之前的68％提高为84.5％，反应时间缩短至2h，同时反应产物中也没有三取代产物的存在，单取代EGCG脂肪酸酯的比例也提高至86.6％。由此可见，微波辅助合成可明显加快反应速度，提高反应转化率。从而提供一种高效、快速、符合绿色化学的合成方法。Beneficial effect of the present invention: the method for synthesizing EGCG fatty acid ester provided by the present invention utilizes the advantage of microwave-assisted synthesis, can reach the effect that reaction does not have under the conventional heating condition, and the reaction conversion rate is improved to 84.5% by 68% before , the reaction time was shortened to 2h, and there was no trisubstituted product in the reaction product, and the ratio of monosubstituted EGCG fatty acid ester also increased to 86.6%. It can be seen that microwave-assisted synthesis can significantly speed up the reaction rate and improve the reaction conversion rate. Therefore, an efficient, rapid and green chemical synthesis method is provided.
附图说明Description of drawings
图1为实施例1中EGCG棕榈酰化产物质谱分析图；图中，信号峰457为未反应EGCG分子离子峰，质核比为169的负离子碎片峰为EGCG结构中的没食子酰基，由于棕榈酰基的分子量为239，因此EGCG分子中每取代一个棕榈酰基，分子量就会增加138，所以图中质核比为695的峰是EGCG的棕榈酰基一取代产物离子峰，质核比为933的峰是EGCG的棕榈酰基二取代产物离子峰。Fig. 1 is the mass spectrum analysis figure of EGCG palmitoylation product in embodiment 1; In the figure, signal peak 457 is unreacted EGCG molecular ion peak, and mass-to-nucleus ratio is the anion fragment peak of 169 is the galloyl group in the EGCG structure, because palmitoyl group The molecular weight of EGCG is 239, so every time a palmitoyl group is substituted in the EGCG molecule, the molecular weight will increase by 138, so the peak with a mass-to-core ratio of 695 in the figure is the palmitoyl-substituted product ion peak of EGCG, and the peak with a mass-to-core ratio of 933 is EGCG palmitoyl disubstitution product ion peak.
图2为实施1中EGCG棕榈酰化产物的液相色谱图，其中峰1，峰2为主要EGCG单取代产物，占反应产物的86.6％。Figure 2 is a liquid chromatogram of EGCG palmitoylation products in Embodiment 1, wherein peaks 1 and 2 are the main EGCG monosubstituted products, accounting for 86.6% of the reaction products.
图3为对比实例1中EGCG棕榈酰化产物的液相色谱图，其中峰1，峰2为主要EGCG单取代产物，占反应产物的52.8％。Figure 3 is a liquid chromatogram of EGCG palmitoylation products in Comparative Example 1, wherein peak 1 and peak 2 are the main EGCG monosubstituted products, accounting for 52.8% of the reaction products.
具体实施方式Detailed ways
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书附图对本发明的具体实施方式做详细的说明。In order to make the above objects, features and advantages of the present invention more obvious and comprehensible, specific implementations of the present invention will be described in detail below in conjunction with the accompanying drawings.
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。In the following description, a lot of specific details are set forth in order to fully understand the present invention, but the present invention can also be implemented in other ways different from those described here, and those skilled in the art can do it without departing from the meaning of the present invention. By analogy, the present invention is therefore not limited to the specific examples disclosed below.
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。Second, "one embodiment" or "an embodiment" referred to herein refers to a specific feature, structure or characteristic that may be included in at least one implementation of the present invention. "In one embodiment" appearing in different places in this specification does not all refer to the same embodiment, nor is it a separate or selective embodiment that is mutually exclusive with other embodiments.
实施例1：Example 1:
将2.2g EGCG溶解于60mL乙酸乙酯置于100mL三口烧瓶中，再加入4.6g碳酸氢钠，将三口烧瓶置于微波反应器中，启动微波反应器，设定反应温度60℃，通过恒压滴液漏斗缓慢滴加6.8g棕榈酰氯，反应2h，反应液经过滤、碱洗、水洗、减压浓缩、重结晶，干燥6h，得到2.84g淡黄色EGCG棕榈酸酯，回收率为78.6％。经高效液相色谱分析EGCG的转化率为85.2％，其中单取代EGCG棕榈酸酯占反应产物的86.6％。Dissolve 2.2g of EGCG in 60mL of ethyl acetate and place in a 100mL three-necked flask, then add 4.6g of sodium bicarbonate, place the three-necked flask in a microwave reactor, start the microwave reactor, set the reaction temperature to 60°C, and pass constant pressure Slowly add 6.8g of palmitoyl chloride dropwise into the dropping funnel, react for 2 hours, the reaction solution is filtered, washed with alkali, washed with water, concentrated under reduced pressure, recrystallized, and dried for 6 hours to obtain 2.84g of light yellow EGCG palmitate with a recovery rate of 78.6%. The conversion rate of EGCG was analyzed by high performance liquid chromatography to be 85.2%, and the monosubstituted EGCG palmitate accounted for 86.6% of the reaction product.
EGCG棕榈酰化产物质谱分析如图1所示。The mass spectrometry analysis of EGCG palmitoylation products is shown in Figure 1.
图中信号峰457为未反应EGCG分子离子峰，质核比为169的负离子碎片峰为EGCG结构中的没食子酰基。由于棕榈酰基的分子量为239，因此EGCG分子中每取代一个棕榈酰基，分子量就会增加138，所以图中质核比为695的峰是EGCG的棕榈酰基一取代产物离子峰，质核比为933的峰是EGCG的棕榈酰基二取代产物离子峰。The signal peak 457 in the figure is the unreacted EGCG molecular ion peak, and the anion fragment peak with a mass-to-core ratio of 169 is the galloyl group in the EGCG structure. Since the molecular weight of palmitoyl is 239, the molecular weight will increase by 138 every time a palmitoyl group is substituted in the EGCG molecule, so the peak with a mass-to-core ratio of 695 in the figure is the ion peak of the palmitoyl-substituted product of EGCG, with a mass-to-core ratio of 933 The peak is the palmitoyl disubstituted product ion peak of EGCG.
图2是实施例1中EGCG棕榈酰化产物的液相色谱图，其中峰1，峰2为主要EGCG单取代产物，占反应产物的86.6％。Figure 2 is a liquid chromatogram of EGCG palmitoylation products in Example 1, wherein peaks 1 and 2 are the main EGCG monosubstituted products, accounting for 86.6% of the reaction products.
对比实例1Comparative example 1
将2.2g EGCG溶解于60mL乙酸乙酯置于100mL三口烧瓶中，再加入4.6g碳酸氢钠，将三口烧瓶置于60℃恒温水浴锅中，恒温水浴加热，通过恒压滴液漏斗缓慢滴加6.8g棕榈酰氯，反应2h，停止反应后，反应液经过滤、碱洗、水洗、减压浓缩、重结晶干燥6h，，得到0.96g淡黄色EGCG棕榈酸酯，回收率为32.8％。经高效液相色谱分析EGCG的转化率为18.6％，其中单取代EGCG棕榈酸酯占反应产物的52.8％。Dissolve 2.2g EGCG in 60mL ethyl acetate and place in a 100mL three-necked flask, then add 4.6g sodium bicarbonate, place the three-necked flask in a constant temperature water bath at 60°C, heat it in a constant temperature water bath, and slowly drop it through a constant pressure dropping funnel 6.8g of palmitoyl chloride was reacted for 2 hours. After the reaction was stopped, the reaction solution was filtered, washed with alkali, washed with water, concentrated under reduced pressure, and recrystallized and dried for 6 hours to obtain 0.96g of light yellow EGCG palmitate with a recovery rate of 32.8%. The conversion rate of EGCG was analyzed by high performance liquid chromatography to be 18.6%, and the monosubstituted EGCG palmitate accounted for 52.8% of the reaction product.
图3是对比实例1中EGCG棕榈酰化产物的液相色谱图，其中峰1，峰2为主要EGCG单取代产物，占反应产物的52.8％。Figure 3 is a liquid chromatogram of EGCG palmitoylation products in Comparative Example 1, wherein peaks 1 and 2 are the main EGCG monosubstituted products, accounting for 52.8% of the reaction products.
实施例2：Example 2:
将4.6g EGCG溶解于120mL四氢呋喃置于250mL三口烧瓶中，再加入10.2g碳酸钠，将三口烧瓶置于微波反应器中，启动微波反应器，设定反应温度60℃，通过恒压滴液漏斗缓慢滴加15.6g硬脂酰氯，反应2.5h，停止反应后，反应液经过滤、碱洗、水洗、减压浓缩、重结晶，然后冷冻干燥5h，得到5.69g淡黄色EGCG硬脂酸酯，回收率为76.3％。经高效液相色谱分析EGCG的转化率为83.6％。Dissolve 4.6g EGCG in 120mL tetrahydrofuran and put it in a 250mL three-necked flask, then add 10.2g sodium carbonate, place the three-necked flask in a microwave reactor, start the microwave reactor, set the reaction temperature at 60°C, and pass through a constant pressure dropping funnel Slowly add 15.6g of stearyl chloride dropwise and react for 2.5h. After stopping the reaction, the reaction solution is filtered, washed with alkali, washed with water, concentrated under reduced pressure, recrystallized, and then freeze-dried for 5h to obtain 5.69g of light yellow EGCG stearate. The recovery rate was 76.3%. The conversion rate of EGCG was analyzed by high performance liquid chromatography to be 83.6%.
实施例3Example 3
将1.2gEGCG溶解于40mL N，N-二甲基乙酰胺置于100mL三口烧瓶中，再加入2.64g三乙胺，将三口烧瓶置于微波反应器中，启动微波反应器，设定反应温度50℃，通过恒压滴液漏斗缓慢滴加3.12g月桂酸酰氯，反应2h，停止反应后，反应液经过滤、碱洗、水洗、减压浓缩、重结晶，然后冷冻干燥6h，得到1.45g淡黄色EGCG月桂酸酯，回收率为78.8％。经高效液相色谱分析EGCG的转化率为86.4％。Dissolve 1.2g of EGCG in 40mL of N,N-dimethylacetamide and place in a 100mL three-necked flask, then add 2.64g of triethylamine, place the three-necked flask in a microwave reactor, start the microwave reactor, and set the reaction temperature to 50 ℃, slowly drop 3.12g of lauric acid chloride through a constant pressure dropping funnel, react for 2h, stop the reaction, the reaction solution is filtered, washed with alkali, washed with water, concentrated under reduced pressure, recrystallized, and then freeze-dried for 6h to obtain 1.45g of lauric acid chloride Yellow EGCG laurate, the recovery rate is 78.8%. The conversion rate of EGCG was analyzed by high performance liquid chromatography to be 86.4%.
实施例4Example 4
将2.3g EGCG溶解于60mL N，N-二甲基乙酰胺置于100mL三口烧瓶中，再加入4.45g吡啶，将三口烧瓶置于微波反应器中，启动微波反应器，设定反应温度60℃，通过恒压滴液漏斗缓慢滴加7.4g棕榈酰氯，反应2.5h，停止反应后，反应液经过滤、碱洗、水洗、减压浓缩、重结晶，然后冷冻干燥6h，得到2.76g淡黄色EGCG棕榈酸酯，回收率为76.2％。经高效液相色谱分析EGCG的转化率为84.1％。Dissolve 2.3g of EGCG in 60mL of N,N-dimethylacetamide and place in a 100mL three-necked flask, then add 4.45g of pyridine, place the three-necked flask in a microwave reactor, start the microwave reactor, and set the reaction temperature to 60°C , slowly drop 7.4g of palmitoyl chloride through the constant pressure dropping funnel, react for 2.5h, stop the reaction, the reaction solution is filtered, washed with alkali, washed with water, concentrated under reduced pressure, recrystallized, and then freeze-dried for 6h to obtain 2.76g of light yellow EGCG palmitate, the recovery rate was 76.2%. The conversion rate of EGCG was analyzed by high performance liquid chromatography to be 84.1%.
由此可见，本发明所提供的合成EGCG脂肪酸酯的方法利用微波辅助合成的优点，能达到常规加热条件下反应所不具备的效果。微波辐射能使反应体系均匀受到微波场的作用，体系升温速度快，温度均匀且保持稳定，可明显加快反应速度，提高反应产率，提高反应转化率。从而提供一种高效、快速、符合绿色化学的合成方法。It can be seen that the method for synthesizing EGCG fatty acid ester provided by the present invention utilizes the advantages of microwave-assisted synthesis, and can achieve the effect that the reaction under conventional heating conditions does not have. Microwave radiation can make the reaction system evenly affected by the microwave field, the system can heat up quickly, and the temperature is uniform and stable, which can obviously speed up the reaction speed, increase the reaction yield, and increase the reaction conversion rate. Therefore, an efficient, rapid and green chemical synthesis method is provided.
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention without limitation, although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be carried out Modifications or equivalent replacements without departing from the spirit and scope of the technical solution of the present invention shall be covered by the claims of the present invention.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510683671.7A CN105884738B (en) | 2015-10-20 | 2015-10-20 | A kind of method of Microwave-assisted synthesis EGCG aliphatic esters |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510683671.7A CN105884738B (en) | 2015-10-20 | 2015-10-20 | A kind of method of Microwave-assisted synthesis EGCG aliphatic esters |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105884738A CN105884738A (en) | 2016-08-24 |
| CN105884738B true CN105884738B (en) | 2018-06-01 |
Family
ID=57002760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510683671.7A Active CN105884738B (en) | 2015-10-20 | 2015-10-20 | A kind of method of Microwave-assisted synthesis EGCG aliphatic esters |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105884738B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115777815A (en) * | 2022-11-21 | 2023-03-14 | 深圳市深宝华城科技有限公司 | Fresh extract of high-concentration fen-flavor oolong tea and preparation method thereof |
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 |
-
2015
- 2015-10-20 CN CN201510683671.7A patent/CN105884738B/en active Active
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 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105884738A (en) | 2016-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102417491B (en) | Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material | |
| CN105218506B (en) | A method of isocoumarin class compound is prepared by o-Halogen benzoic acids methyl esters and terminal alkyne | |
| CN103664536A (en) | Synthetic method of hydroxytyrosol | |
| CN109320479A (en) | A kind of simple synthesis of Ascorbyl Tetraisopalmitate | |
| CN104672291B (en) | A kind of preparation method of gallic acid plant sterol ester | |
| CN105884738B (en) | A kind of method of Microwave-assisted synthesis EGCG aliphatic esters | |
| CN102993179A (en) | Preparation method of high-purity sodium rabeprazole | |
| CN104945383B (en) | Hold in the palm his preparation method of pyrrole department | |
| CN102329263A (en) | Preparation method of N-acetyl-5-methoxytryptamine | |
| CN103450005B (en) | A kind of preparation method of clopidogrel and the alpha-brominated (2-Chlorophenyl)acetic acid of intermediate and α-thiophene ethamine base substituted acetic acid hydrochlorate | |
| CN106699594B (en) | A kind of preparation method of Iopromide | |
| CN106983872A (en) | A kind of docosahexaenoic acid is coupled the preparation method of Docetaxel targeted drug | |
| CN106928152A (en) | A kind of preparation method of uracil | |
| CN108794441B (en) | Baicalein phenolic hydroxyl esterified derivative, pharmaceutical composition and application thereof | |
| CN104072409B (en) | A kind of synthetic method of pyridine amides | |
| CN105061372B (en) | A kind of synthetic method of aphthofurans class compound | |
| CN109400432A (en) | The preparation method and application of hydroxytyrosol ester type compound | |
| CN104230739B (en) | N, the technique of N, N-thricyclohexyl-1,3,5-benzamide is produced with trimesic acid | |
| CN105622408A (en) | Method for preparing bi (2-micristin) calcium urea compound | |
| CN110845667A (en) | A kind of synthetic method of anti-tumor activity bagasse xylan phytate-g-BMA | |
| CN102838649A (en) | Preparation method of abiraterone acetate | |
| CN104292201A (en) | Method for preparing 3-ester group catechin | |
| CN108929249A (en) | A kind of new technique for synthesizing of ethyl creatine ester hydrochloride | |
| CN105566422B (en) | The preparation method of Suo Feibuwei intermediate or derivatives thereof | |
| CN114716434B (en) | Nicergoline bulk drug and synthesis process thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DD01 | Delivery of document by public notice |
Addressee: Wang Xiaodong Document name: Notification of Passing Examination on Formalities Addressee: Zhang Luyi Document name: Notification of Passing Examination on Formalities |
|
| DD01 | Delivery of document by public notice |
Addressee: Wang Xiaodong Document name: Notice of conformity |
|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP02 | Change in the address of a patent holder |
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 |
|
| CP02 | Change in the address of a patent holder |