A method for synthesizing vitamin E succinate by catalysis of deep eutectic solvent and lipase

Abstract

The present invention provides a method for synthesizing vitamin E succinate catalyzed by lipase in a low eutectic solvent, belonging to the field of biocatalysis technology. The low eutectic solvent is synthesized by a heating and stirring method using the fatty acid n-decanoic acid as a hydrogen bond acceptor and lidocaine as a hydrogen bond donor. The low eutectic solvent prepared by this method has the advantages of maintaining enzymatic properties and good substrate solubility, and can be used to catalyze the esterification reaction of vitamin E and succinic anhydride to prepare vitamin E succinate. The method can be carried out at a relatively low temperature of 50°C, the reaction is rapid and only takes 6 hours, the amount of lipase used is small (only 4% substrate mass ratio is required), the conditions are mild, and the yield of vitamin E succinate is as high as 95.67%. The present invention provides a new method for synthesizing vitamin E succinate in a green and efficient manner.

Description

Technical Field

[0001] The invention belongs to the technical field of biocatalysis, and particularly relates to a method for synthesizing vitamin E succinate by esterification reaction of vitamin E and succinic anhydride catalyzed by lipase in a low eutectic solvent. Background Art

[0002] As an important essential substance, vitamin E plays a key role in our health, growth and development, and shows great advantages in the fields of food and medicine. However, the phenolic hydroxyl group of vitamin E is easily oxidized by air and heat, which poses a major challenge to the production, transportation and storage of vitamin E. In addition, fat-soluble vitamin E is almost insoluble in water, which makes them unable to be effectively absorbed in the body. The absorption and utilization rate of vitamin E after esterification is significantly improved. In addition, traditional vitamin E products are mostly oily and difficult to make into tablets and hard capsules, while vitamin E succinate is crystalline at room temperature, so it does not have the above defects. In addition, the higher melting point of vitamin E succinate also enables it to withstand the extreme conditions in the drug granulation process, making the final product more stable.

[0003] The chemical synthesis of vitamin E succinate mainly uses triethylamine, pyridine or acid and base as catalysts. It has disadvantages such as being environmentally unfriendly, using volatile organic solvents, chemical catalyst residues, dark product color, and high separation and refining costs. In 2009, Zheng Yansheng et al. used 4-dimethylaminopyridine as a catalyst and vitamin E and succinic anhydride as raw materials to synthesize vitamin E succinate. Under the optimized conditions of a succinic anhydride to vitamin E molar ratio of 3:1, a catalyst dosage of 0.05 g (accounting for 1.5% of the raw material), an acetone solvent dosage of 10 mL, a reaction temperature of 50°C, and a reaction time of 4 h, the yield reached 88.57% (Zheng Yansheng, Mo Qian. Synthesis and Stability Study of Vitamin E Succinate [J]. Chemistry and Bioengineering, 2009, 26 (4): 26-28). Compared with chemical synthesis, enzymatic synthesis has the advantages of mild reaction conditions, high catalytic efficiency, and strong catalytic specificity. It is a green and efficient synthesis route that has attracted widespread attention in recent years.

[0004] The literature reports that the process of enzyme-catalyzed synthesis of vitamin E succinate generally has problems such as long reaction time, easy loss of enzyme activity when using traditional highly polar organic solvents, and difficulty in ensuring the quality of the final product. In 2010, Yin Chunhua et al. optimized the synthesis process of vitamin E succinate, using Candida sp. lipase to catalyze the reaction, which required 71 hours of reaction in a mixed solvent of dimethyl sulfoxide and tert-butyl alcohol (Yin Chunhua, Liu Jiangfan, Gao Ming. Enzymatic Synthesis and Optimization of Vitamin E Succinate [J]. Journal of Chemical Industry, 2010, 61(04): 935-940.). In 2013, Jiang Xiangjun et al. used dimethyl sulfoxide as the reaction solvent and obtained only a yield of 46.95% after 18 hours of reaction (Xiangjun Jiang, Yi Hu, Lin Jiang, Jihong Gong, He Huang. Synthesis of vitamin E succinate using Candida rugosa lipase inorganic medium. Chemical Research in Chinese University, 2013, 29 (2): 223-226). These all indicate that the efficiency of enzymatic synthesis of vitamin E succinate in traditional organic solvents is not high.

[0005] Solvents determine the sustainability and safety of chemical processes. Traditional organic solvents such as dimethyl sulfoxide, tert-butyl alcohol and acetone have the disadvantages of high volatility, high toxicity and difficulty in recycling. They are harmful to human health and have an adverse impact on the ecological environment during the synthesis of vitamin E succinate. The most common synthesis method of vitamin E esters is through the esterification reaction of vitamin E and the corresponding acid anhydride. Due to the huge differences in polarity and affinity for water between these two substrates, dimethyl sulfoxide, acetone and other highly polar organic solvents were mostly used as reaction media in the past. However, the easy inactivation of lipase in highly polar organic solvents has become a stumbling block to its application. Summary of the invention

[0006] The technical problem solved by the present invention is: the present invention provides a method for preparing vitamin E succinate by catalyzing the esterification of vitamin E and succinic anhydride in a low eutectic solvent synthesized by a heating and stirring method using Candida plicata lipase as a catalyst. The hydrogen bond acceptor n-decanoic acid and the hydrogen bond donor lidocaine are mixed in a molar ratio of 2:1 and stirred until a clear and uniform liquid is formed, and a low eutectic solvent is successfully synthesized. The method can be carried out at a relatively low temperature of 50°C, the reaction is rapid and only takes 6 hours, the amount of lipase used is small (only 4% substrate mass ratio is required), the conditions are mild, and the yield of vitamin E succinate is as high as 95.67%.

[0007] In order to solve the above technical problems, the technical solution proposed by the present invention is: a method for lipase-catalyzed synthesis of vitamin E succinate in a deep eutectic solvent, wherein a hydrogen bond acceptor n-decanoic acid and a hydrogen bond donor lidocaine are mixed at a molar ratio of 2:1 at a certain temperature by a heating and stirring method, and stirred until a clear and uniform liquid is formed, and a deep eutectic solvent is successfully synthesized, and the synthesized deep eutectic solvent is cooled to room temperature, and a deep eutectic solvent and a certain amount of Candida plicata lipase are added to a reactor, and vitamin E and succinic anhydride in a certain molar ratio are added under heating and stirring conditions to carry out an esterification reaction, and the reaction route is as follows:

[0008]

[0009] Preferably, the specific preparation steps of the deep eutectic solvent include:

[0010] (1) Add hydrogen bond acceptors and hydrogen bond donors into a magnetic stirrer at 50°C;

[0011] (2) Stir at 300 r / min until a clear and uniform liquid is formed.

[0012] Preferably, the molar ratio of vitamin E to succinic anhydride is 1:4.

[0013] Preferably, the reaction time of the esterification reaction is 6 hours; the reaction temperature of the esterification reaction is 50° C., and the amount of the lipase added in the reaction is 4% by weight of the total substrate.

[0014] Preferably, a deep eutectic solvent is synthesized by a heating stirring method, 6.89 g (0.04 mol) of capric acid and 4.68 g (0.02 mol) of lidocaine are mixed, and mixed thoroughly on a magnetic stirrer at 50° C. and 300 r / min until a clear and transparent solution is formed, to obtain a deep eutectic solvent with a ratio of capric acid to lidocaine of 2:1; then, the synthesized deep eutectic solvent is cooled to room temperature;

[0015] 1 mmol vitamin E and 4 mmol succinic anhydride were added to a 15 mL reaction tube, and then 4% substrate mass ratio of Candida rugosa lipase and 5 mL of the above-mentioned low eutectic solvent were added, and stirred at 50° C. After reacting for 6 hours, the reaction yield was monitored by liquid phase U3000; the yield of vitamin E succinate was 95.67%.

[0016] A method for synthesizing vitamin E succinate catalyzed by lipase in a deep eutectic solvent, wherein the preparation method of the deep eutectic solvent is as follows: a selected hydrogen bond acceptor and a hydrogen bond donor are mixed at a designed molar ratio at a designed temperature by a heating and stirring method, and stirred until a clear and uniform liquid is formed, thereby successfully synthesizing a deep eutectic solvent. Subsequently, the synthesized deep eutectic solvent is cooled to room temperature. Lipase is added to a reactor, and vitamin E and succinic anhydride are added under heating and stirring conditions to perform an esterification reaction.

[0017] The specific preparation steps of the deep eutectic solvent include:

[0018] (1) At a certain temperature, a certain molar ratio of hydrogen bond acceptor and hydrogen bond donor is added into a magnetic stirrer.

[0019] (2) Stir at a certain speed until a clear and uniform liquid is formed.

[0020] The molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 2:1-4:1, preferably 1:2.

[0021] The heating and stirring temperature is 35-100°C, preferably 50°C.

[0022] The lipase is one of Candida plicata lipase, Pseudomonas cepacia lipase, porcine pancreatic lipase, Candida lipase or Burkholderia cepacia lipase, preferably Candida plicata lipase.

[0023] The hydrogen bond acceptor is n-decanoic acid, the hydrogen bond donor is lidocaine, the molar ratio is 2:1, the lipase is Candida plicata lipase, the molar ratio of vitamin E and succinic anhydride is 1:4, the reaction temperature is 50°C, the amount of lipase added is 4% based on the total mass percentage of the substrate, and the reaction time is 6 hours.

[0024] The hydrogen bond acceptor is one of fatty acids. The low eutectic solvent hydrogen bond acceptor is a fatty acid such as capric acid, lauric acid, etc., and the hydrogen bond donor is lidocaine. Preferably, the low eutectic solvent is composed of capric acid and lidocaine in a ratio of 2:1.

[0025] The molar ratio of vitamin E to succinic anhydride is 1:1-1:7, preferably 1:4.

[0026] The lipase is added in the esterification reaction in an amount of 1%-10% based on the total mass percentage of the substrate, preferably 4%.

[0027] The reaction temperature of the esterification reaction is 35-70°C, and the preferred reaction temperature is 50°C.

[0028] The esterification reaction time is 4-24 hours, and the preferred reaction time is 6 hours.

[0029] Beneficial effects:

[0030] (1) Low eutectic solvents have the characteristics of low cost, 100% atomic utilization, and good biocompatibility, making them excellent solvents for biocatalysis.

[0031] (2) The low eutectic solvent synthesized by the heating and stirring method of the present invention is a hydrophobic low eutectic solvent, which can stabilize the activity and stability of the enzyme on the one hand, and can synergistically catalyze with lipase to improve the yield of vitamin E succinate on the other hand.

[0032] (3) The present invention uses a low eutectic solvent to greenly synthesize vitamin E succinate, which can not only improve the catalytic activity and stability of the enzyme, but also reduce the reaction time and improve the reaction efficiency. The low eutectic solvent of the present invention is simple to prepare, has low toxicity, high thermal stability and biodegradability, and is a substitute for traditional toxic and harmful organic solvents and ionic liquids. It has adjustable hydrophilicity and hydrophobicity, highly adjustable physicochemical properties, and excellent solubility for organic and inorganic compounds.

[0033] (4) Under the conditions of preferred embodiment 1, the hydrogen bond acceptor is n-decanoic acid, the hydrogen bond donor is lidocaine, the molar ratio is 2:1, the lipase is Candida plicata lipase, the molar ratio of vitamin E to succinic anhydride is 1:4, the reaction temperature is 50°C, the amount of lipase added is 4% based on the total mass percentage of the substrate, and the reaction time is 6h. The optimal reaction yield is 95.67%. Compared with the previous enzymatic synthesis of vitamin E succinate, the reaction time is very short, the reaction time is 6 hours, and the low lipase dosage is 4% to obtain a high reaction yield of 95.67%.

[0034] (5) In Example 2, the molar ratio of capric acid to lidocaine was changed while other conditions remained unchanged, capric acid: lidocaine = 3:1 or 4:1. It was found that as the proportion of capric acid increased, the yield of vitamin E succinate gradually decreased.

[0035] (6)) Example 3 shows that when the type of fatty acid is changed while other conditions remain unchanged, it is found that as the carbon chain length changes, whether it is lengthening lauric acid or shortening caprylic acid, the reaction yield decreases to varying degrees.

[0036] (7) Example 4 shows that when the types of hydrogen bond donors and hydrogen bond acceptors are changed while other conditions remain unchanged, it is found that the esterification reaction hardly occurs in common low eutectic solvents. The types of low eutectic solvents tried also include: hydrogen bond acceptors such as choline chloride, betaine, menthol, thymol, diethylaminoethanol hydrochloride, etc.; hydrogen bond donors such as urea, glycerol, ethylene glycol, lithium chloride, indole, etc., and almost no reaction occurs.

[0037] (8) Example 5 shows that when the other conditions remain unchanged, the type of lipase is changed to porcine pancreatic lipase or Candida lipase. It can be found that the reaction yield decreases to varying degrees with the change of the type of lipase.

[0038] (9) Example 6 shows that the molar ratio of vitamin E to succinic anhydride was changed while other conditions remained unchanged. It can be found that as the molar ratio of the substrate changes, the molar ratio of vitamin E to succinic anhydride is 1:1 or 1:7, and the reaction yield decreases to varying degrees.

[0039] (10) It can be seen from Examples 7 and 8 that when the amount of lipase is reduced while other conditions remain unchanged, the reaction yield decreases as the amount of lipase decreases. When the amount of lipase is increased while other conditions remain unchanged, the reaction yield decreases as the amount of lipase increases to 10%.

[0040] (11) Examples 9 and 10 show that when the temperature of the esterification reaction is lowered to 30°C while other conditions remain unchanged, it can be found that the reaction yield decreases as the temperature decreases. When the temperature of the esterification reaction is raised to 70°C while other conditions remain unchanged, it can be found that the reaction yield decreases as the temperature increases.

[0041] (12) Example 12 shows that when the conventional organic solvent dimethyl sulfoxide was used under the same conditions, the reaction yield decreased to only 38.92%. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The present invention is further described below in conjunction with the accompanying drawings.

[0043] Figure 1 The synthesis schematic diagram of the reaction of the present invention is

[0044] Figure 2 The low eutectic solvent in Example 1 of the present invention is decanoic acid: lidocaine = 2:1 1 HNMR spectrum.

[0045] Figure 3 The low eutectic solvent in Example 2 of the present invention is decanoic acid: lidocaine = 3:1 1 HNMR spectrum.

[0046] Figure 4 The low eutectic solvent in Example 3 of the present invention is decanoic acid: lidocaine = 4:1 1 HNMR spectrum.

[0047] Figure 5 is the vitamin E succinate in Example 1 of the present invention 1 HNMR spectrum.

[0048] Figure 6 This is a viscosity curve of the low eutectic solvent capric acid: lidocaine = 2 / 3 / 4:1 in Examples 1, 2, and 3 of the present invention.

[0049] Figure 7 This is a thermogravimetric analysis diagram of the low eutectic solvent of decanoic acid: lidocaine = 2 / 3 / 4:1 in Examples 1, 2, and 3 of the present invention. DETAILED DESCRIPTION

[0050] The present invention is further described below with reference to the following examples. The examples listed are for illustration only and indicate that the spirit and scope of the present invention are not limited to the details and modifications therein.

[0051] The biological enzymes and other reagents involved in the present invention are all purchased from the market, and none of the reagents are further purified; liquid phase U3000 is used for the quantitative and qualitative determination of vitamin E succinate.

[0052] Embodiment 1:

[0053] The deep eutectic solvent was synthesized by the heating and stirring method. 6.89 g (0.04 mol) of capric acid and 4.68 g (0.02 mol) of lidocaine were mixed and fully mixed on a magnetic stirrer at 50°C and 300 r / min until a clear and transparent solution was formed to obtain a low eutectic solvent with a ratio of capric acid to lidocaine of 2:1. Subsequently, the synthesized low eutectic solvent was cooled to room temperature.

[0054] 1 mmol vitamin E and 4 mmol succinic anhydride were added to a 15 mL reaction tube, and then 4% substrate mass ratio of Candida rugosa lipase and 5 mL of the above-mentioned deep eutectic solvent were added, and stirred at 50° C. After 6 hours of reaction, the reaction yield was monitored by liquid phase U3000.

[0055] Vitamin E and vitamin E succinate were quantitatively analyzed by high performance liquid chromatography. A high performance liquid chromatograph produced by Shimadzu Corporation of Japan was used, and the chromatographic column was C 18 Reverse column (250mm×4mm, 5μm), SPD-20A VP UV-Vis detector at 285nm to detect reactants and products, mobile phase is methanol-glacial acetic acid (500:3.2), flow rate is 0.8mL / min, column temperature is 30℃, injection volume is 10μl. Standard curve is established with pure vitamin E succinate, product yield is determined by external standard method, and the yield of vitamin E succinate is 95.67%.

[0056] Under the preferred conditions, the best reaction yield was 95.67%. Compared with the previous enzymatic method for synthesizing vitamin E succinate, a high reaction yield of 95.67% was achieved with an extremely short reaction time of 6 hours and a lower lipase dosage of 4%.

[0057] Embodiment 2:

[0058] The low eutectic solvent was synthesized by the heating and stirring method. 10.33g (0.06mol), 13.78g (0.08mol) capric acid and 4.68g (0.02mol) lidocaine were mixed and fully mixed on a magnetic stirrer at 50°C and 300r / min until a clear and transparent solution was formed, and a low eutectic solvent of capric acid: lidocaine = 3:1 or 4:1 was obtained. 1mmol vitamin E and 4mmol succinic anhydride were added to a 15mL reaction tube, and then 4% substrate mass ratio of Candida plicata lipase was added, and 5mL of the above low eutectic solvent was added respectively, and stirred at 50°C. After 6 hours of reaction, the reaction yield was monitored by liquid phase U3000. The quantitative method refers to Example 1, and the yields of vitamin E succinate are 91.30% and 85.89%, respectively.

[0059] While other conditions remained unchanged, the molar ratio of capric acid to lidocaine was changed to capric acid: lidocaine = 3:1 or 4:1. It was found that with the increase of the capric acid ratio, the yield of vitamin E succinate gradually decreased.

[0060] Embodiment 3:

[0061] The low eutectic solvent was synthesized by the heating and stirring method. 12.02g (0.06mol) of lauric acid or 8.65g (0.06mol) of n-octanoic acid and 4.68g (0.02mol) of lidocaine were mixed and fully mixed on a magnetic stirrer at 50°C and 300r / min until a clear and transparent solution was formed to obtain a low eutectic solvent of lauric acid / n-octanoic acid: lidocaine = 3:1. 1mmol vitamin E and 4mmol succinic anhydride were added to a 15mL reaction tube, and then 4% substrate mass ratio of Candida rugosa lipase, 5mL of the above low eutectic solvent were added and stirred at 50°C. After 6 hours of reaction, the reaction yield was monitored by liquid phase U3000. Quantitative method Referring to Example 1, the yields of vitamin E succinate were 81.72% and 85.29%, respectively.

[0062] By changing the type of fatty acid while keeping other conditions unchanged, it was found that the reaction yield decreased to varying degrees with the change of carbon chain length, whether it was lengthening lauric acid or shortening caprylic acid.

[0063] Embodiment 4:

[0064] The low eutectic solvent was synthesized by the heating and stirring method. 5.58g (0.04mol) of choline chloride and 1.20g (0.02mol) of urea were mixed and fully mixed on a magnetic stirrer at 45°C and 300r / min until a clear and transparent solution was formed to obtain a low eutectic solvent of choline chloride: urea = 2:1. 1mmol vitamin E and 4mmol succinic anhydride were added to a 15mL reaction tube, and then 4% substrate mass ratio of Candida plicata lipase, 5mL of the above low eutectic solvent were added, and stirred at 50°C. After 6 hours of reaction, the reaction yield was monitored by liquid phase U3000. Quantitative method Referring to Example 1, the yield of vitamin E succinate was 3.09%.

[0065] The types of hydrogen bond donors and hydrogen bond acceptors were changed while other conditions remained unchanged, and it was found that the esterification reaction hardly occurred in common low eutectic solvents. The types of low eutectic solvents tried also included: hydrogen bond acceptors such as choline chloride, betaine, menthol, thymol, diethylaminoethanol hydrochloride, etc.; hydrogen bond donors such as urea, glycerol, ethylene glycol, lithium chloride, indole, etc., and almost no reaction occurred.

[0066] Embodiment 5:

[0067] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2: 1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 4% substrate mass ratio of porcine pancreatic lipase or Candida lipase, 5mL of the above-mentioned low eutectic solvent are added, and stirred at 50°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yields of vitamin E succinate are 82.33% and 84.70%, respectively.

[0068] When the types of lipase were changed while other conditions remained unchanged, it was found that the reaction yield decreased to varying degrees with the change of the types of lipase.

[0069] Embodiment 6:

[0070] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2: 1 is referred to Example 1. 1mmol vitamin E and 1mmol or 7mmol succinic anhydride are added to a 15mL reaction tube, and then 4% substrate mass ratio of Candida plicata lipase, 5m: the above low eutectic solvent are added, and stirred at 50°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 48.33% and 91.03%.

[0071] The molar ratio of vitamin E to succinic anhydride was changed while other conditions remained unchanged. The molar ratio of vitamin E to succinic anhydride was 1:1 or 1:7. It can be found that the reaction yield decreased to varying degrees with the change of the substrate molar ratio.

[0072] Embodiment 7:

[0073] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2:1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 1% substrate mass ratio of Candida rugosa lipase and 5mL of the above low eutectic solvent are added, and stirred at 50°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 59.03%.

[0074] When the dosage of lipase was reduced while other conditions remained unchanged, it was found that the reaction yield decreased with the reduction of the dosage of lipase.

[0075] Embodiment 8:

[0076] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2:1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 10% substrate mass ratio of Candida rugosa lipase and 5mL of the above low eutectic solvent are added, and stirred at 50°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 92.37%.

[0077] When the dosage of lipase was increased while other conditions remained unchanged, it was found that as the dosage of lipase increased to 10%, the reaction yield decreased.

[0078] Embodiment 9:

[0079] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2: 1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 4% substrate mass ratio of Antarctic Candida lipase and 5mL of the above low eutectic solvent are added, and stirred at 30°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 72.13%.

[0080] When the other conditions remained unchanged, the temperature of the esterification reaction was lowered to 30°C. It was found that the reaction yield decreased with the decrease in temperature.

[0081] Embodiment 10:

[0082] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2: 1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 4% substrate mass ratio of Antarctic Candida lipase and 5mL of the above low eutectic solvent are added, and stirred at 70°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 60.41%.

[0083] When the temperature of the esterification reaction was raised to 70°C while other conditions remained unchanged, it was found that the reaction yield decreased with the increase in temperature.

[0084] Embodiment 11:

[0085] The synthesis process of the low eutectic solvent of decanoic acid: lidocaine = 2: 1 is referred to Example 1. 1mmol vitamin E and 4mmol succinic anhydride are added to a 15mL reaction tube, and then 4% substrate mass ratio of Candida plicata lipase and 5mL of the above low eutectic solvent are added, and stirred at 40°C. After 1h and 24h of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yields of vitamin E succinate are 28.06% and 93.27%, respectively.

[0086] When the time of esterification reaction was changed while other conditions remained unchanged, it was found that the reaction yield decreased to varying degrees with the change of time.

[0087] Embodiment 12:

[0088] 1 mmol vitamin E and 4 mmol succinic anhydride were added to a 15 mL reaction tube, and then 4% substrate mass ratio of Candida plicata lipase and 5 mL dimethyl sulfoxide were added, and stirred at 40°C. After 6 hours of reaction, the reaction yield was monitored by liquid phase U3000. The quantitative method was referred to Example 1, and the yield of vitamin E succinate was 38.92%

[0089] When the traditional organic solvent dimethyl sulfoxide was used under the same conditions, it was found that the reaction yield decreased to only 38.92%.

[0090] Example 13

[0091] The synthesis process of the deep eutectic solvent of decanoic acid: lidocaine = 2:1 is referred to Example 1. 1 mmol vitamin E and 4 mmol succinic anhydride are added to a 15 mL reaction tube, 5 mL of the above-mentioned deep eutectic solvent is stirred at 50°C. After 6 hours of reaction, the reaction yield is monitored by liquid phase U3000. The quantitative method is referred to Example 1, and the yield of vitamin E succinate is 34.91%.

[0092] When other conditions remain unchanged and lipase is not added, it can be found that the deep eutectic solvent itself can catalyze the esterification reaction. When the deep eutectic solvent and lipase catalyze the reaction synergistically, a better yield can be obtained than when the two catalyze the reaction alone.

[0093] The present invention is not limited to the specific technical solutions described in the above embodiments, and all technical solutions formed by equivalent replacement are within the protection scope required by the present invention.

Claims

1. A method for synthesizing vitamin E succinate by catalysis of a deep eutectic solvent and lipase, characterized in that: The method comprises: (1) The hydrogen bond acceptor n-decanoic acid and the hydrogen bond donor lidocaine were mixed in a molar ratio of 2:1, stirred at 50°C and 300 r / min until a clear and uniform liquid was formed to synthesize a low eutectic solvent and cooled to room temperature; (2) Add vitamin E and succinic anhydride in a molar ratio of 1:4, 4% of the total mass of the substrate Candida plicata lipase and the low eutectic solvent synthesized in step (1) into the reactor, and carry out esterification reaction under heating and stirring conditions. The reaction route is as follows: ； The reaction time of the esterification reaction is 6 h; the reaction temperature of the esterification reaction is 50°C.

2. The method for synthesizing vitamin E succinate by catalysis of a deep eutectic solvent and lipase according to claim 1, characterized in that: Step (1) is to add a hydrogen bond acceptor n-decanoic acid and a hydrogen bond donor lidocaine in a molar ratio of 2:1 into a magnetic stirrer; stir at 50°C and 300 r / min until a clear and uniform liquid is formed and cool to room temperature.

3. The method for synthesizing vitamin E succinate by synergistic catalysis using a deep eutectic solvent according to claim 1, characterized in that: The method comprises: (1) Add 6.89 g of decanoic acid and 4.68 g of lidocaine into a magnetic stirrer, and stir at 50° C. and 300 r / min until a clear and uniform liquid is formed to obtain a low eutectic solvent; then, cool the synthesized low eutectic solvent to room temperature; (2) 1 mmol of vitamin E and 4 mmol of succinic anhydride were added to a 15 mL reaction tube, and then 4% of the substrate amount of Candida albicans lipase and 5 mL of the low eutectic solvent synthesized in step (1) were added; after stirring the reaction at 50 °C for 6 hours, the reaction yield was monitored using a liquid phase U3000; the yield of vitamin E succinate was 95.67%.

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