CN117587081A - Alpha-tocopheryl succinate and preparation method thereof - Google Patents
Alpha-tocopheryl succinate and preparation method thereof Download PDFInfo
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- tocopherol
- succinic anhydride
- tocopheryl succinate
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- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims abstract description 92
- 229940087168 alpha tocopherol Drugs 0.000 claims abstract description 46
- 229960000984 tocofersolan Drugs 0.000 claims abstract description 46
- 239000002076 α-tocopherol Substances 0.000 claims abstract description 46
- 235000004835 α-tocopherol Nutrition 0.000 claims abstract description 46
- 108090001060 Lipase Proteins 0.000 claims abstract description 37
- 239000004367 Lipase Substances 0.000 claims abstract description 37
- 102000004882 Lipase Human genes 0.000 claims abstract description 37
- 235000019421 lipase Nutrition 0.000 claims abstract description 37
- XMXLVNVGGJBUPF-UHFFFAOYSA-N 2-amino-n,n-diethyl-1,3-benzothiazole-6-carboxamide Chemical compound CCN(CC)C(=O)C1=CC=C2N=C(N)SC2=C1 XMXLVNVGGJBUPF-UHFFFAOYSA-N 0.000 claims abstract description 36
- 108050004181 Proto-oncogene Mas Proteins 0.000 claims abstract description 36
- 102000015925 Proto-oncogene Mas Human genes 0.000 claims abstract description 36
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229940014800 succinic anhydride Drugs 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 238000004090 dissolution Methods 0.000 claims abstract description 4
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 claims description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000011347 resin Substances 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 238000004132 cross linking Methods 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 4
- 238000007334 copolymerization reaction Methods 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 69
- 239000000758 substrate Substances 0.000 abstract description 12
- 239000000047 product Substances 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 239000007795 chemical reaction product Substances 0.000 abstract description 2
- 230000001276 controlling effect Effects 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 108090000790 Enzymes Proteins 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 16
- 230000003197 catalytic effect Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000002194 synthesizing effect Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 108010048733 Lipozyme Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000007036 catalytic synthesis reaction Methods 0.000 description 4
- FCCDDURTIIUXBY-UHFFFAOYSA-N lipoamide Chemical compound NC(=O)CCCCC1CCSS1 FCCDDURTIIUXBY-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
- 108010084311 Novozyme 435 Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108010093096 Immobilized Enzymes Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000013406 biomanufacturing process Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- -1 ester compound Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 150000003772 α-tocopherols Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Pyrane Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention discloses a preparation method of alpha-tocopheryl succinate, which comprises the following steps: adding alpha-tocopherol and succinic anhydride into an organic solvent, oscillating for dissolution, adding immobilized lipase MAS1, and carrying out catalytic reaction at 30-60 ℃ to obtain the catalyst; the addition amount of the immobilized lipase MAS1 is 6-30% of the total MASs of the alpha-tocopherol and the succinic anhydride. The invention adopts immobilized lipase MAS1 as a catalyst, and can synthesize alpha-tocopheryl succinate in a short time by regulating and controlling the addition amount of lipase, the mole ratio of a substrate and the reaction temperature in the reaction process, thereby improving the reaction rate, reducing the energy consumption loss, ensuring the high purity of the reaction product, ensuring the product quality and being beneficial to the subsequent separation and purification. The whole process flow is simple and convenient, has low production cost and is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of biochemical engineering, and particularly relates to alpha-tocopheryl succinate and a preparation method thereof.
Background
Vitamin E is an indispensable nutrient in the human body and is also a recognized natural antioxidant, and has been widely used in the fields of medicine, food and cosmetics. Vitamin E has eight homologs in nature, of which alpha-tocopherol is the most common and most active, and is therefore known primarily as alpha-tocopherol.
Since the hydroxyl group on the benzene ring of alpha-tocopherol is easily oxidized, the alpha-tocopherol is unstable under the condition of air or weak oxidant, which brings certain difficulties to the preparation and storage of the alpha-tocopherol. O-acylating the hydroxyl group of alpha-tocopherol to form corresponding ester compound can improve the stability and possess many other functions and properties. Among a series of alpha-tocopherol derivatives, alpha-tocopherol succinate is the most prominent in biological activity, and is a potential tumor therapeutic drug which can effectively assist in cancer treatment. In view of the medical value of alpha-tocopheryl succinate, researchers have conducted related studies on the synthesis of alpha-tocopheryl succinate for several decades.
U.S. patent No. 3459774 provides a method for synthesizing vitamin E succinate by reacting in acetic acid solvent with zinc powder at 100-140 ℃ using anhydrous sodium acetate as catalyst. Japanese patent JP170757 explores a method for synthesizing vitamin E succinate with methyl ethyl ketone as solvent and triethylamine as catalyst. Chinese patent CN100560580C discloses a synthesis process of vitamin E succinate. The triethanolamine is used as a catalyst, a substrate and a solvent are placed in a reaction kettle to react for 2 to 5 hours at the temperature of 80 to 125 ℃, and nitrogen is required to be introduced in the whole reaction process. The above-mentioned patent techniques all use chemical methods to synthesize alpha-tocopheryl succinate, which suffer from several drawbacks: (1) Catalysts such as pyridine and tertiary amine used are toxic; (2) the reaction temperature is too high, and the energy consumption is high; (3) The high temperature condition is easy to oxidize and denature alpha-tocopherol, and the product quality is reduced.
Compared with chemical method, the enzyme catalytic method has mild reaction condition and strong selectivity, and has wide application in catalyzing and synthesizing ester substances. The method for synthesizing the natural alpha-tocopherol succinate monoester by adopting lipase disclosed in CN101475968B has the advantages of strong specificity and less byproducts, but has slow dynamics (72 hours, the conversion rate reaches 80-98 percent) and low reaction rate, and can seriously influence the industrial production efficiency.
It is therefore desirable to find a process technology that can efficiently synthesize alpha-tocopheryl succinate.
Disclosure of Invention
Based on this, the object of the present invention is to provide a process for producing alpha-tocopherol succinate, which can synthesize alpha-tocopherol succinate of high purity in a short time and with high conversion.
The technical scheme for realizing the aim of the invention comprises the following steps.
In a first aspect of the present invention, there is provided a process for the preparation of alpha-tocopheryl succinate comprising the steps of: adding alpha-tocopherol and succinic anhydride into an organic solvent, oscillating for dissolution, adding immobilized lipase MAS1, and carrying out catalytic reaction at 30-60 ℃ to obtain the catalyst; the addition amount of the immobilized lipase MAS1 is 6-30% of the total MASs of the alpha-tocopherol and the succinic anhydride.
In a second aspect of the invention, there is provided an alpha-tocopheryl succinate prepared by the above-described method.
The invention has the following beneficial effects:
the invention adopts immobilized lipase MAS1 as a catalyst, and can synthesize alpha-tocopheryl succinate in a short time by regulating and controlling the addition amount of lipase, the mole ratio of a substrate and the reaction temperature in the reaction process, thereby improving the reaction rate, reducing the energy consumption loss, ensuring the high purity of the reaction product, ensuring the product quality and being beneficial to the subsequent separation and purification. The whole process flow is simple and convenient, has low production cost and is suitable for industrial production.
Drawings
FIG. 1 shows the conversion of various lipases used in example 1 of the present invention to catalyze the synthesis of alpha-tocopheryl succinate.
FIG. 2 shows the conversion of the free enzyme MAS1 and the immobilized enzyme MAS1 in example 2 of the present invention to α -tocopherol succinate.
FIG. 3 shows the conversion of various solvents to synthetic alpha-tocopheryl succinate in example 3 of the present invention.
FIG. 4 shows the conversion of the synthesis of alpha-tocopheryl succinate at various temperatures in example 4 of the present invention.
FIG. 5 shows the conversion of synthetic alpha-tocopheryl succinate with different substrate molar ratios in example 5 according to the present invention.
FIG. 6 shows the conversion of the various amounts of immobilized enzyme added to the synthesis of alpha-tocopheryl succinate in example 6 of the present invention.
Detailed Description
The present invention will be described more fully hereinafter in order to facilitate an understanding of the present invention. This invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
The experimental procedures, which do not address the specific conditions in the examples below, are generally carried out under conventional conditions or under conditions recommended by the manufacturer. The various chemicals commonly used in the examples are commercially available.
In the invention, the inventor selects MAS1 from several immobilized lipases as an enzyme catalyst of alpha-tocopheryl succinate, the conversion rate of the immobilized lipases to alpha-tocopheryl is high and reaches 90%, on the basis, the addition of the immobilized lipases MAS1 is further optimized (when the addition of the enzymes is 12% -30% of the total MASs of alpha-tocopheryl and succinic anhydride, the conversion rate is over 80%, when the addition of the enzymes is 12% -24% of the total MASs of alpha-tocopheryl and succinic anhydride, the conversion rate is over 98%, when the addition of the enzymes is 18% of the total MASs of alpha-tocopheryl and succinic anhydride, the conversion rate is over 99%, the kind of reaction solvents (when the reaction solvents are DMSO, the catalytic efficiency is up to 90%), the molar ratio of reaction substrates (when the molar ratio is 1:2-1:5, the conversion rate is over 80%, the molar ratio is 1:3-1:4, the conversion rate is highest), the catalytic reaction temperature (40-60 ℃) is 80%, the conversion rate is higher than 50-60 ℃), the conversion rate is higher than 50 ℃, the conversion rate is higher, the conversion rate is lower than the conversion rate is higher than the conversion rate is lower than the highest, the conversion rate is better than the conversion rate is lower than the maximum, the conversion rate is more than the conversion rate is under the conditions of 4h, the conversion rate is higher than the conversion rate is high, the conversion rate is more than the final, the conversion rate is better is not can be guaranteed, the product is more than the product is better, and the quality is better is separated, and can be purified, and can be obtained, and can reach the final product, and has high, and high quality. In addition, the preparation method provided by the invention has the advantages of simple and convenient whole process flow and low production cost, and is suitable for industrial production.
In some embodiments of the present invention, a method for preparing alpha-tocopheryl succinate is disclosed, comprising the steps of: adding alpha-tocopherol and succinic anhydride into an organic solvent, oscillating for dissolution, adding immobilized lipase MAS1, and carrying out catalytic reaction at 30-60 ℃ to obtain alpha-tocopherol succinate; the addition amount of the immobilized lipase MAS1 is 6-30% of the total MASs of the alpha-tocopherol and the succinic anhydride.
In some of these embodiments, the immobilized lipase MAS1 is added in an amount of 6% to 24% of the total MASs of alpha-tocopherol and succinic anhydride; preferably from 12% to 24% of the total mass of alpha-tocopherol and succinic anhydride, more preferably 18% of the total mass of alpha-tocopherol and succinic anhydride.
In some of these embodiments, the temperature of the catalytic reaction is 40 to 60 ℃, preferably 50 to 60 ℃, more preferably 50 ℃.
In some of these embodiments, the organic solvent is DMSO or DMF, preferably DMSO.
In some of these embodiments, the molar ratio of alpha-tocopherol to succinic anhydride is from 1:1 to 1:5, preferably from 1:3 to 1:5, more preferably from 1:3 to 1:4.
In some embodiments, the immobilized lipase MAS1 is immobilized by physical adsorption, covalent bonding, crosslinking, entrapment, copolymerization, or empty vector immobilization; adsorption crosslinking is preferred.
In some of these embodiments, the carrier in the empty carrier immobilization is resin AP, resin D5753, and/or resin ECR 8285.
In other embodiments of the present invention, alpha-tocopheryl succinate prepared by the above-described preparation method is disclosed.
In the following examples, MAS1 was derived from Guangdong Utility Biomanufacturing institute, inc.; novozym435, lipozyme TL IM, lipozyme RM IM were derived from Norwegian communications.
The invention is described in detail below with reference to the drawings and the specific embodiments.
Example 1 Effect of different immobilized lipases on the catalytic efficiency of alpha-tocopheryl succinate
After adding 0.43g of alpha-tocopherol, 0.3g of succinic anhydride and 5 mM SO in each of the 4 triangular flasks with stoppers and shaking at 40℃until the substrate was completely dissolved, immobilized lipases MAS1, novozym435, lipozyme TL IM and Lipozyme RM IM were added respectively according to the same enzyme activity (50U). The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the results are shown in FIG. 1.
As can be seen from fig. 1, the conversion rate of the commercial lipase novozyme 435 for catalytic synthesis of alpha-tocopherol succinate is lower than 20%, the conversion rate of the lipase Lipozyme TL for IM catalytic synthesis of alpha-tocopherol succinate is lower than 60%, the conversion rate of the lipase Lipozyme RM for IM catalytic synthesis of alpha-tocopherol succinate is lower than 40%, and the conversion rate of the immobilized lipase MAS1 as a catalyst for catalytic synthesis of alpha-tocopherol succinate reaches about 90%. Therefore, the lipase MAS1 has very excellent catalytic effect and can be used for efficiently synthesizing alpha-tocopheryl succinate.
In this example, after the reaction was completed, immobilized lipase MAS1 was recovered by filtration and washing, the filtrate was distilled under reduced pressure to remove the solvent, diethyl ether was added and allowed to stand at low temperature for 12 hours, then filtration was carried out, excess succinic anhydride was removed, diethyl ether was distilled under reduced pressure to obtain a pale yellow oily substance, and finally, the pale yellow oily substance was dissolved in n-hexane and then cooled to crystallize to obtain an α -tocopherol succinate product, the purity of which was 99%.
Example 2 Effect of free Lipase MAS1 and immobilized Lipase MAS1 on the catalytic efficiency of alpha-tocopheryl succinate
After adding 0.43g of alpha-tocopherol, 0.3g of succinic anhydride and 5 mM SO in each of the 2 triangular flasks with stoppers, and shaking at 40℃until the substrate was completely dissolved, the free lipase MAS1 and the immobilized lipase MAS1 were added, respectively, according to the same enzyme activity (50U). The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the results are shown in FIG. 2.
The result shows that the conversion rate of the free enzyme MAS1 for catalyzing and synthesizing alpha-tocopheryl succinate is less than 10%, and the catalysis efficiency of the immobilized lipase MAS1 is obviously better than that of the free enzyme MAS1.
Example 3 Effect of organic solvent on the catalytic efficiency of alpha-tocopheryl succinate
Taking 6 triangular flasks with plugs, respectively adding 5ml of LDMSO, DMF, acetonitrile, isopropanol, ethyl acetate and n-hexane, respectively adding 0.43g of alpha-tocopherol and 0.3g of succinic anhydride, and after shaking at 40 ℃ until the substrates are completely dissolved, respectively adding immobilized lipase MAS1 accounting for 12% of the total MASs of the alpha-tocopherol and the succinic anhydride. The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the result is shown in FIG. 3.
The results show that the conversion rate of alpha-tocopherol is lower than 50% by taking DMF, acetonitrile, isopropanol, ethyl acetate and n-hexane as reaction solvents, and the conversion rate in DMSO can reach more than 85%, and the alpha-tocopherol succinate can be used as an organic solvent for synthesizing alpha-tocopherol succinate.
Example 4 influence of the reaction temperature on the catalytic efficiency of alpha-tocopheryl succinate
Into each of the 4 triangular flasks with stopper, 0.43g of alpha-tocopherol, 0.3g of succinic anhydride and 5ml of LDMSO were added, and after shaking at 30℃and 40℃and 50℃and 60℃until the substrate was completely dissolved, immobilized lipase MAS1 was added in an amount of 12% based on the total MASs of alpha-tocopherol and succinic anhydride. The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the result is shown in FIG. 4.
The results show that when the temperature is increased from 30 ℃ to 50 ℃, the conversion rate of alpha-tocopherol is increased from 60% to 90%, and when the temperature is increased to 60 ℃, the conversion rate is slightly reduced. Therefore, the synthesis of alpha-tocopheryl succinate is best at a temperature of 50 ℃.
Example 5 influence of the molar ratio of the reaction substrates on the catalytic efficiency of alpha-tocopheryl succinate
To each of the 6 triangular flasks with stoppers, 0.43g of alpha-tocopherol and 5ml of LDMSO were added, and 0.1g, 0.2g, 0.3g, 0.4g, and 0.5g of succinic anhydride (molar ratio: 1:1, 1:2, 1:3, 1:4, and 1:5, respectively) were added, respectively, and after shaking at 50℃until the substrate was completely dissolved, immobilized lipase MAS1 was added in an amount of 12% based on the total MASs of alpha-tocopherol and succinic anhydride. The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the result is shown in FIG. 5.
The results show that increasing the amount of succinic anhydride increases the conversion of alpha-tocopherol from 1:1 to 1:4, the conversion increases by 33% and the molar ratio of alpha-tocopherol to succinic anhydride increases from 1:4 to 1:5, the conversion instead decreasing. Therefore, the synthesis of alpha-tocopheryl succinate is best when the molar ratio of alpha-tocopherol to succinic anhydride is 1:4.
Example 6 Effect of the enzyme addition amount of immobilized Lipase MAS1 on the catalytic efficiency of alpha-tocopheryl succinate
After adding 0.43g of alpha-tocopherol, 0.4g of succinic anhydride and 5 mM SO in 5 triangular flasks with stoppers and shaking at 50℃until the substrate was completely dissolved, 6%, 12%, 18%, 24% and 30% of immobilized lipase MAS1 by total MASs of alpha-tocopherol and succinic anhydride were added, respectively. The reaction was carried out at 150rpm for 24 hours, and the conversion of alpha-tocopherol was measured, and the result is shown in FIG. 6.
The results show that the enzyme addition is higher in catalytic activity when the enzyme addition is between 6 and 30 percent, the conversion rate of alpha-tocopherol is more than 80 percent when the enzyme addition is between 12 and 30 percent, and the conversion rate is relatively higher when the enzyme addition is more than 12 to 24 percent. The catalytic effect is optimal when the enzyme addition amount is 18 percent.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. A process for the preparation of alpha-tocopheryl succinate comprising the steps of: adding alpha-tocopherol and succinic anhydride into an organic solvent, oscillating for dissolution, adding immobilized lipase MAS1, and carrying out catalytic reaction at 30-60 ℃ to obtain the catalyst; the addition amount of the immobilized lipase MAS1 is 6-30% of the total MASs of the alpha-tocopherol and the succinic anhydride.
2. The method for producing alpha-tocopheryl succinate according to claim 1, wherein the amount of the immobilized lipase MAS1 added is 12% to 30% of the total MASs of alpha-tocopherol and succinic anhydride.
3. The method for producing alpha-tocopheryl succinate according to claim 2, wherein the immobilized lipase MAS1 is added in an amount of 12% to 24% of the total MASs of alpha-tocopherol and succinic anhydride, more preferably 18% of the total MASs of alpha-tocopherol and succinic anhydride.
4. The process for the preparation of alpha-tocopheryl succinate according to claim 1, wherein the temperature of the catalytic reaction is 40-60 ℃, preferably 50-60 ℃, more preferably 50 ℃.
5. The method for preparing alpha-tocopheryl succinate according to claim 1, wherein the organic solvent is DMSO or DMF, preferably DMSO.
6. The method for producing alpha-tocopherol succinate according to claim 1, wherein the molar ratio of the alpha-tocopherol to the succinic anhydride is 1:1 to 1:5.
7. The method for producing alpha-tocopherol succinate according to claim 6, wherein the molar ratio of the alpha-tocopherol to succinic anhydride is 1:3 to 1:5, more preferably 1:3 to 1:4.
8. The method for producing α -tocopherol succinate according to any one of claims 1-7, wherein the immobilized lipase MAS1 is immobilized by physical adsorption, covalent bonding, crosslinking, entrapment, copolymerization, or empty carrier immobilization; adsorption crosslinking is preferred.
9. The method for producing alpha-tocopheryl succinate according to claim 8, wherein the carrier in the empty carrier fixation is resin AP, resin D5753, and/or resin ECR 8285.
10. The alpha-tocopheryl succinate prepared by the method of any one of claims 1 to 9.
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