A method for the enzymatic in-line synthesis of vitamin b6 esters

Abstract

The application provides a method for enzymatic online synthesis of vitamin B6 ester, wherein vitamin B6 and fatty acid vinyl ester are used to catalyze the online synthesis of vitamin B6 ester by using lipase Lipozyme RM IM in a micro-fluid channel reactor. The method not only greatly shortens the reaction time, but also has high conversion rate; meanwhile, the esterification reaction of vitamin B6 and fatty acid vinyl ester is catalyzed by using economical lipase Lipozyme RM IM for the first time, the reaction cost is reduced, and the method has the advantages of economy and efficiency.

Description

TECHNICAL FIELD

[0001] The present application relates to a method for synthesizing vitamin B6 ester online. BACKGROUND

[0002] Vitamin B6 is a natural pyridine derivative, including pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and its phosphorylated derivatives, which plays an important role in the body. Endogenous metabolites of vitamin B6, pyridoxal phosphate and pyridoxamine phosphate, are important coenzymes involved in the metabolism of amino acids, carbohydrates, fatty acids, lipids, and the synthesis of nucleic acids, hemoglobin, serotonin, dopamine, norepinephrine, and GABA neurotransmitters, with physiological functions such as blood pressure regulation and neuroprotection. Due to the special role of vitamin B6 in cells, the design of drug molecules based on the structure of vitamin B6 provides a new idea for new drug development.

[0003] However, vitamin B6 has poor stability and poor fat solubility, which affects its production, storage and absorption. The low fat solubility of vitamin B6 is not conducive to the absorption of skin and cells, limiting its application in drug development. In order to overcome the defects of vitamin B6 in physical and chemical properties and expand its application range, so that it can be better stored and absorbed by the human body, in recent years, the esterification modification of vitamin B6 and the design and synthesis of new vitamin B6 derivatives have become a research hotspot for medicinal chemists.

[0004] Esterification reaction is usually carried out under strong acid or strong base conditions, but harsh reaction conditions increase the number of side reactions, which is not conducive to the synthesis of vitamin B6. Enzymatic reaction has become a focus of green chemistry research due to its high efficiency, greenness and strong specificity. Enzymatic reaction has been widely used in industrial biosynthesis, medical care and food industry due to its mild reaction conditions, high selectivity and good product stability. However, enzymatic reaction has some restrictions such as solvent solubility of substrate and inhibition of enzyme activity by solvent polarity, and the reaction time is often very long (24h-96h), and the conversion rate of specific substrate is not very high. Therefore, developing a new technology for enzymatic synthesis of vitamin B6 ester based on microfluidic technology on the basis of traditional enzymatic reaction has become our research goal.

[0005] Compared with conventional chemical reactors, microfluidic reactors have high mixing efficiency, fast mass and heat transfer, precise parameter control, high reaction selectivity and good safety, and are widely used in organic synthesis reactions. In continuous flow microreactors, many reactions can achieve rapid screening of microscale reaction conditions, and safe reactions can be carried out even under harsh experimental conditions, greatly saving reaction raw materials and improving screening efficiency, making it more in line with the concept of green chemistry.

[0006] So far, the research on enzyme-catalyzed synthesis of vitamin B6 ester is relatively less. Lipase B from Candida antarctica (Lipase B from Candida antarctica) can effectively catalyze the reaction, but the method needs a long reaction time (72 h). In order to develop a new technology of efficient and green synthesis of vitamin B6 ester, we studied the method of lipase-catalyzed online synthesis of vitamin B6 ester in continuous flow microreactor, aiming to find a new technology of efficient and green synthesis of vitamin B6 ester. SUMMARY

[0007] The present application aims to provide a new process method for online synthesis of vitamin B6 ester in a microfluidic channel reactor, which has the advantages of short reaction time and high yield.

[0008] To achieve the above-mentioned purpose, the technical scheme of the present application is as follows:

[0009] A method for online synthesis of vitamin B6 ester, the method comprising:

[0010] The method uses a microfluidic channel reactor, which comprises a syringe, a reaction channel and a product collector connected in sequence, the syringe is installed in a syringe pump, the syringe is connected with the inlet of the reaction channel through a first connecting pipeline, the product collector is connected with the outlet of the reaction channel through a second connecting pipeline, the inner diameter of the reaction channel is 1.6-2.2 mm (preferably 2.0 mm), and the length of the reaction channel is 0.8-1.2 m (preferably 1.0 m);

[0011] The method comprises:

[0012] A reaction system is constructed with methanol as the reaction solvent, vitamin B6 represented by formula (I) and fatty acid vinyl ester represented by formula (II) as raw materials, and lipase Lipozyme RM IM as the catalyst; the raw materials and the reaction solvent are placed in the syringe, the lipase Lipozyme RM IM is uniformly filled in the reaction channel of the microfluidic channel reactor, under the synchronous pushing of the syringe pump, the raw materials and the reaction solvent are continuously fed into the reaction channel to carry out the Michael addition reaction, the reaction temperature is controlled at 25-50°C (preferably 30°C), the reaction time of the reaction liquid continuously flowing in the reaction channel is 10-60 min (preferably 20 min), the reaction liquid flowing out of the reaction channel is collected online by the product collector, and the reaction liquid is treated to obtain vitamin B6 ester represented by formula (III);

[0013]

[0014] In formula (II) and (III), R is CH3, (CH2)4COOC2H3, C11 H 23 or C 15 H 31 (preferably CH3) ;

[0015] The molar ratio of vitamin B6 of formula (I) to fatty acid vinyl ester of formula (II) is 1:0.5-5 (particularly preferably 1:4) ; the amount of catalyst added is 0.030 g / mL-0.060 g / mL (preferably 0.043 g / mL) based on the volume of the reaction solvent within the maximum capacity of the reaction channel; the concentration of vitamin B6 of formula (I) in the reaction system is 0.1 mmol / mL-0.4 mmol / mL (preferably 0.25 mmol / mL).

[0016] The lipase Lipozyme RM IM is a commercial product of Novozymes, which is a preparation of a 1,3-specific, food-grade lipase (EC 3.1.1.3) on granular silica gel, which is obtained from Rhizomucor miehei and produced by deep fermentation of a genetically modified Aspergillus oryzae microorganism; the lipase Lipozyme RM IM can be directly and uniformly fixed in the reaction channel by physical method; the amount of catalyst added is 0.043 g / mL based on the volume of the reaction medium within the maximum capacity of the reaction channel;

[0017] Further, the number of injectors in the microfluidic channel reactor used in the present application can be one or more, depending on the specific reaction requirements. The present application uses two kinds of reaction raw materials, preferably two injectors. Specifically, the injectors are a first injector and a second injector, the first connecting pipeline is a Y-shaped or T-shaped pipeline, the first injector and the second injector are connected to two interfaces of the Y-shaped or T-shaped pipeline respectively and are connected in series with the reaction channel through the Y-shaped or T-shaped pipeline, the contact and collision probability of reactant molecules through the microchannel is increased, so that the two streams of reaction liquid are mixed and reacted in the common reaction channel. That is, the microfluidic channel reactor of the method of the present application comprises a first injector, a second injector, a reaction channel and a product collector; the first injector and the second injector are connected to the inlet of the reaction channel through a Y-shaped or T-shaped pipeline, and the product collector is connected to the outlet of the reaction channel through a pipeline.

[0018] Further, vitamin B6 of formula (I) and fatty acid vinyl ester of formula (II) are dissolved in methanol respectively to obtain vitamin B6 solution and fatty acid vinyl ester solution, which are introduced into the reaction channel through the first and second syringes respectively. The concentration of vitamin B6 of formula (I) in the vitamin B6 solution is 0.2 mmol / mL to 0.8 mmol / mL (preferably 0.5 mmol / mL), and the concentration of fatty acid vinyl ester of formula (II) in the fatty acid vinyl ester solution is 0.5 mmol / mL to 2.5 mmol / mL (preferably 2 mmol / mL).

[0019] Further, the present application provides a method for synthesizing vitamin B6 ester online, which uses a microfluidic channel reactor, the microfluidic channel reactor comprises syringes, a reaction channel and a product collector connected in sequence, the syringes are installed in a syringe pump, the syringes are connected with the inlet of the reaction channel through a first connecting pipeline, the product collector is connected with the outlet of the reaction channel through a second connecting pipeline, the inner diameter of the reaction channel is 1.6 mm to 2.2 mm (preferably 2.0 mm), and the length of the reaction channel is 0.8 m to 1.2 m (preferably 1.0 m); the syringes are a first syringe and a second syringe, the first connecting pipeline is a Y-shaped or T-shaped pipeline, the first syringe and the second syringe are connected with two interfaces of the Y-shaped or T-shaped pipeline respectively and are connected with the reaction channel in series through the Y-shaped or T-shaped pipeline;

[0020] The method is as follows: vitamin B6 of formula (I) and fatty acid vinyl ester of formula (II) are respectively dissolved in methanol to obtain a vitamin B6 solution of formula (I) with a concentration of 0.2-0.8 mmol / mL (preferably 0.5 mmol / mL) and a fatty acid vinyl ester solution of formula (II) with a concentration of 0.5-2.5 mmol / mL (preferably 2 mmol / mL); the vitamin B6 solution of formula (I) and the fatty acid vinyl ester solution of formula (II) are respectively loaded into the first and second syringes, and the first and second syringes are loaded into the same injection pump; after the lipase Lipozyme RM IM is uniformly filled in the reaction channel of the microfluidic channel reactor, the vitamin B6 solution of formula (I) and the fatty acid vinyl ester solution of formula (II) are continuously and synchronously fed into the reaction channel under the synchronous pushing of the injection pump to perform a Michael addition reaction, the reaction temperature is controlled to be 30-55°C (preferably 40°C), the reaction liquid continuously flows in the reaction channel for 10-60 min (preferably 40 min), the reaction liquid flowing out of the reaction channel is collected on line by a product collector, and the reaction liquid is subjected to post-treatment to obtain vitamin B6 ester of formula (III); the concentration ratio of the vitamin B6 solution of formula (I) to the fatty acid vinyl ester solution of formula (II) is 1:1-5 (particularly preferably 1:4); the amount of the catalyst added is 0.03-0.06 g / mL (preferably 0.043 g / mL) of the volume of the reaction solvent within the maximum capacity of the reaction channel for accommodating the filled catalyst.

[0021] Further, the post-treatment is as follows: the solvent in the reaction liquid is removed by evaporation under reduced pressure, a mixed solution of methanol and dichloromethane with a volume ratio of 1:10 is used as an eluent for silica gel column chromatography, the eluate containing the target compound is collected, and the solvent is evaporated and dried to obtain vitamin B6 ester of formula (III).

[0022] Specifically, the post-treatment method is as follows: the solvent in the reaction liquid is removed by evaporation under reduced pressure, silica gel is wet-packed into a column with a mesh size of 200-300, a mixed solution of methanol and dichloromethane with a volume ratio of 1:10 is used as an eluent, the elution process is tracked by TLC, the eluate containing the target compound is collected, the solvent is evaporated and dried, and the product vitamin B6 ester (III) is obtained.

[0023] The method of the application uses a microfluidic channel reactor, which comprises a first syringe, a second syringe, a reaction channel and a product collector; the first and second syringes are connected to the inlet of the reaction channel through a Y-shaped or T-shaped pipeline, and the product collector is connected to the outlet of the reaction channel through a pipeline.

[0024] The inner diameter of the reaction channel is 2.0 mm, and the length of the reaction channel is 1.0 m; the material of the reaction channel is not limited, and green and environmentally friendly materials such as silica gel tubes are recommended; the shape of the reaction channel is preferably curved, which can ensure that the reaction liquid passes through stably and uniformly;

[0025] The microfluidic channel reactor can also comprise a thermostat, and the reaction channel is placed in the thermostat, so that the reaction temperature can be effectively controlled; the thermostat can be selected according to the requirement of the reaction temperature, such as a water bath thermostat.

[0026] Compared with the prior art, the beneficial effects of the present application are:

[0027] The vitamin B6 ester is synthesized in the microfluidic channel reactor, which greatly shortens the reaction time and has a high conversion rate; the product obtained after post-treatment has a purity of more than 99%, which can be regarded as a pure product. At the same time, the esterification reaction of the vitamin and the fatty acid vinyl ester is catalyzed by the economical lipase Lipozyme RM IM for the first time, which reduces the reaction cost and has the advantages of economy and efficiency. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 The structure diagram of the microfluidic channel reactor used in the embodiment of the present application.

[0029] In the figure, 1 is a first syringe, 2 is a second syringe, 3 is a reaction channel, 4 is a product collector, and 5 is a water bath thermostat. DETAILED DESCRIPTION

[0030] The present application will be further described below with specific examples, but the protection scope of the present application is not limited thereto:

[0031] The structure of the microfluidic channel reactor used in the embodiment of the present application is shown in Figure 1 , which comprises an injection pump (not shown), two syringes 1 and 2, a reaction channel 3, a water bath thermostat (5, only a plan view is shown), and a product collector 4; the two syringes 1 and 2 are installed in the injection pump and connected with the inlet of the reaction channel 3 through a Y-shaped interface, the reaction channel 3 is placed in the water bath thermostat 5, and the reaction temperature is controlled by the water bath thermostat 5; the inner diameter of the reaction channel 3 is 2.0 mm, and the length of the tube is 1.0 m; the outlet of the reaction channel 3 is connected with the product collector 4 through an interface.

[0032] Example 1: Synthesis of vitamin B6 acetate

[0033]

[0034] Apparatus Figure 1: Vitamin B6 (5.0 mmol, 0.846 g) was dissolved in 10 mL MeOH, vinyl acetate (20.0 mmol, 1.720 g) was dissolved in 10 mL MeOH, then loaded into 10 mL syringes respectively. 0.87 g lipase Lipozyme RM IM was evenly filled in the reaction channel, under the push of PHD 2000 syringe pump, two-way reaction liquid was respectively entered into the reaction channel at a flow rate of 15.7 μL·min -1 The reaction was carried out by controlling the reactor temperature at 30℃ through a water bath constant temperature box, and the reaction liquid was continuously flowed in the reaction channel for 20 min. The reaction results were tracked and detected by thin layer chromatography (TLC).

[0035] The reaction liquid was collected online by the product collector, the solvent was removed by reduced pressure distillation, and the wet column was filled with 200-300 mesh silica gel. The elution reagent was methanol: dichloromethane (volume ratio = 1:10), the column height was 35 cm, the column diameter was 4.5 cm, and the sample was dissolved in a small amount of elution reagent and then wet-loaded onto the column. The eluent was collected at a flow rate of 2 mL·min -1 , and the elution process was tracked by TLC. The obtained eluent containing a single product was combined and evaporated to obtain a white solid. 0.940 g of vitamin B6 acetate was obtained with a separation yield of 89%.

[0036] The nuclear magnetic characterization results are as follows:

[0037] white powder,yield 89%. 1 H NMR (500 MHz, DMSO-d6) δ 9.05 (s, 1H), 7.97 (s, 1H), 5.16 (s, 2H), 4.52 (d, J = 5.9 Hz, 2H), 3.40 (t, J = 5.9 Hz, 1H), 2.50 (s, 3H), 2.03 (s, 3H). . 13 CNMR (126 MHz, DMSO) δ 170.37, 149.60, 146.52, 139.35, 134.71, 127.66, 58.71, 56.91, 20.60, 19.75.

[0038] Example 2-5

[0039] The solvent in the microfluidic microchannel reactor was changed, the temperature was controlled at 30℃, and the others were the same as in Example 1. The results are shown in Table 1:

[0040] Table 1 Effect of solvent on reaction

[0041] Example Solvent Conversion [%] Yield [g] 1 Methanol (10 ml) 89 0.940 2 Acetonitrile (10 ml) <5 0.052 3 Chloroform (10 ml) n.d. 0 4 DMSO (10 ml) 15 0.157 5 Pyridine (10 ml) n.d. 0

[0042] The results of Table 1 show that when the flow rate is 30.4 μL·min -1 , the reaction time is 20 min, the reaction temperature is 30℃, and the reactor uses MeOH as the organic solvent, the conversion rate of the reaction is optimal, so the optimal solvent in the microfluidic microchannel reactor in the present application is methanol.

[0043] Examples 6-10

[0044] The temperature of the microfluidic channel reactor is changed, and the other conditions are the same as in Example 1, and the reaction results are shown in Table 2:

[0045] Table 2: Effect of temperature on the reaction

[0046] Example Temperature [°C] Conversion [%] Yield [g] 6 25 62 0.644 1 30 89 0.940 7 35 82 0.866 8 40 76 0.799 9 45 61 0.644 10 50 49 0.516

[0047] The results of Table 2 show that when the flow rate is 30.4 μL·min -1 , the reaction time is 20 min, the reactor uses MeOH as the organic solvent, the molar ratio of vitamin B6 to vinyl acetate is 1:4, and the reaction temperature is 30℃, the conversion rate of the reaction is optimal, and too high or too low temperature will affect the activity of the enzyme. Therefore, the optimal temperature in the microfluidic microchannel reactor in the present application is 30℃.

[0048] Examples 11-15

[0049] The amount of vitamin B6 is used as a reference, the molar ratio of vitamin B6 to vinyl acetate in the microfluidic microchannel reactor is changed, the temperature is controlled at 30℃, and the other conditions are the same as in Example 1, and the results are shown in Table 3:

[0050] Table 3: Effect of the molar ratio of the substrate on the reaction

[0051] Example Vitamin B6 and vinyl acetate Conversion [%] Yield [g] 11 1 : 0.5 (5.0 mmol : 2.5 mmol, 0.846 g : 0.215 g) 35 0.369 12 1 : 1 (5.0 mmol : 5.0 mmol, 0.846 g : 0.430 g) 59 0.623 13 1 : 2 (5.0 mmol : 10.0 mmol, 0.846 g : 0.860 g) 67 0.708 14 1 : 3 (5.0 mmol : 15.0 mmol, 0.846 g : 1.290 g) 76 0.802 1 1 : 4 (5.0 mmol : 20.0 mmol, 0.846 g : 1.720 g) 89 0.940 15 1 : 5 (5.0 mmol : 25.0 mmol, 0.846 g : 2.150 g) 82 0.864

[0052] The results of Table 3 show that when the flow rate is 30.4 μL·min -1 , the reaction time is 20 min, the reaction temperature is 30℃, the reactor uses MeOH as the organic solvent, and as the amount of the reactant vinyl acetate increases, the conversion rate of the reaction also increases, and when the molar ratio of the substrate vitamin B6 to vinyl acetate is 1:4, the conversion rate of the reaction is optimal, so the optimal molar ratio of the substrate in the microfluidic microchannel reactor in the present application is 1:4.

[0053] Examples 16-20

[0054] The reaction time of the microfluidic channel reactor is changed, and the other conditions are the same as in Example 8, and the reaction results are shown in Table 4:

[0055] Table 4: Effect of reaction time on the reaction

[0056] Example Time [min] Conversion [%] Yield [g] 16 10 65 0.686 1 20 89 0.940 17 30 85 0.898 18 40 75 0.792 19 50 65 0.686 20 60 52 0.549

[0057] The results of Table 4 show that when the reactor uses MeOH as the organic solvent, the molar ratio of the reactants vitamin B6 and vinyl acetate is 1:4, the reaction temperature is 30°C, and the reaction time is 20 min, the conversion rate is 89%. Therefore, the optimal reaction time in the microfluidic microchannel reactor of the present application is 20 min.

[0058] Comparative Examples 1-3

[0059] The type of fatty acid vinyl ester in the microfluidic channel reactor was changed to divinyl adipate, vinyl laurate, and vinyl palmitate, and the other conditions were the same as in Example 1. The results are shown in Table 5.

[0060] Table 6: Effect of different acrylate esters on the conversion rate

[0061] Comparative Example Fatty acid vinyl ester Conversion [%] Yield [g] 1 Adipic acid divinyl ester (20.0 mmol, 3.960 g) 52 0.846 2 Vinyl laurate (20.0 mmol, 4.520 g) 32 0.561 3 Vinyl palmitate (20.0 mmol, 5.640 g) 13 0.255 Example 1 Vinyl acetate (20.0 mmol, 1.720 g) 89 0.940

[0062] The results show that the structure of the different fatty acid vinyl esters has a significant effect on the conversion rate of vitamin B6 ester. In vinyl palmitate, the conversion rate of vitamin B6 is only 13%, while in vinyl acetate, the conversion rate of vitamin B6 is 89%.

[0063] Comparative Examples 4-7

[0064] The catalyst in the microfluidic microchannel reactor was changed to porcine pancreatic lipase PPL, lipase Novozym 435, Bacillus subtilis alkaline protease, and lipase TM IM, respectively, and the other conditions were the same as in Example 1. The results are shown in Table 6.

[0065] Table 6: Effect of different enzymes on the conversion rate and selectivity

[0066]

[0067]

[0068] The results show that different catalysts have a very significant effect on the reaction. Using lipase TM IM to catalyze the reaction, the conversion rate of vitamin B6 is 27%. Using Bacillus subtilis alkaline protease to catalyze the reaction, the conversion rate of vitamin B6 is less than 5%. Therefore, the optimal enzyme source in the microfluidic microchannel reactor of the present application is lipase RM IM.

Claims

1. A method for the online synthesis of vitamin B6 esters, characterized in that: The method adopts a microfluidic channel reactor, the microfluidic channel reactor comprises a syringe, a reaction channel and a product collector connected in sequence, the syringe is installed in a syringe pump, the syringe is connected with the inlet of the reaction channel through a first connecting pipeline, the product collector is connected with the outlet of the reaction channel through a second connecting pipeline, the inner diameter of the reaction channel is 1.6-2.2 mm, and the length of the reaction channel is 0.8-1.2 m; The method comprises: The reaction system is constructed by taking methanol as a reaction solvent, vitamin B6 represented by formula (I) and fatty acid vinyl ester represented by formula (II) as raw materials and lipase Lipozyme RM IM as a catalyst; the raw materials and the reaction solvent are placed in a syringe, the lipase Lipozyme RM IM is uniformly filled in the reaction channel of the microfluidic channel reactor, the raw materials and the reaction solvent are continuously introduced into the reaction channel for a Michael addition reaction under the synchronous pushing of the syringe pump, the reaction temperature is controlled to be 30 DEG C, the reaction liquid continuously flows in the reaction channel for 10-60 min, the reaction liquid flowing out of the reaction channel is collected on line through a product collector, and the reaction liquid is subjected to post-treatment to obtain vitamin B6 ester represented by formula (III). (I) (II) (III) In formulae (II) and (III), R is CH3. The molar ratio of vitamin B6 represented by formula (I) to fatty acid vinyl ester represented by formula (II) is 1:4; the catalyst is added in an amount of 0.030 g / mL-0.060 g / mL based on the volume of the reaction solvent within the maximum limit of the reaction channel; and the concentration of vitamin B6 represented by formula (I) in the reaction system is 0.1 mmol / mL-0.4 mmol / mL.

2. The process for the online synthesis of vitamin B6 esters according to claim 1, characterized in that: The catalyst is added in an amount of 0.043 g / mL based on the volume of the reaction solvent.

3. The process for the online synthesis of vitamin B6 esters according to claim 1, characterized in that: The concentration of vitamin B6 represented by formula (I) in the reaction system is 0.25 mmol / mL.

4. The process for the online synthesis of vitamin B6 esters according to claim 1, characterized in that: The number of the syringes is two.

5. The process for the online synthesis of vitamin B6 esters according to claim 4, characterized in that: The syringes are a first syringe and a second syringe, the first connecting pipeline is a Y-shaped or T-shaped pipeline, and the first syringe and the second syringe are connected to two interfaces of the Y-shaped or T-shaped pipeline and are connected with the reaction channel in series through the Y-shaped or T-shaped pipeline.

6. The process for the online synthesis of vitamin B6 esters according to claim 5, characterized in that: Vitamin B6 represented by formula (I) and fatty acid vinyl ester represented by formula (II) are respectively dissolved in methanol to obtain a vitamin B6 solution and a fatty acid vinyl ester solution, and then the solutions are respectively introduced into the reaction channel through the first syringe and the second syringe, the concentration of vitamin B6 represented by formula (I) in the vitamin B6 solution is 0.2 mmol / mL-0.8 mmol / mL, and the concentration of fatty acid vinyl ester represented by formula (II) in the fatty acid vinyl ester solution is 0.5-2.5 mmol / mL.

7. The method according to claim 4, wherein The method adopts a microfluidic channel reactor, the microfluidic channel reactor comprises a syringe, a reaction channel and a product collector connected in sequence, the syringe is installed in a syringe pump, the syringe is connected with the inlet of the reaction channel through a first connecting pipeline, the product collector is connected with the outlet of the reaction channel through a second connecting pipeline, the inner diameter of the reaction channel is 1.6-2.2 mm, and the length of the reaction channel is 0.8-1.2 m; the syringe is a first syringe and a second syringe, the first connecting pipeline is a Y-shaped or T-shaped pipeline, and the first syringe and the second syringe are connected with two interfaces of the Y-shaped or T-shaped pipeline respectively and are connected with the reaction channel in series through the Y-shaped or T-shaped pipeline; The method is as follows: vitamin B6 shown in formula (I) and fatty acid vinyl ester shown in formula (II) are respectively dissolved in methanol to obtain a vitamin B6 solution shown in formula (I) with a concentration of 0.2 mmol / mL-0.8 mmol / mL and a fatty acid vinyl ester solution shown in formula (II) with a concentration of 0.5-2.5 mmol / mL; the vitamin B6 solution shown in formula (I) and the fatty acid vinyl ester solution shown in formula (II) are respectively filled in the first syringe and the second syringe, and the first syringe and the second syringe are installed in the same syringe pump; after lipase Lipozyme RM IM is uniformly filled in the reaction channel of the microfluidic channel reactor, the vitamin B6 solution shown in formula (I) and the fatty acid vinyl ester solution shown in formula (II) are continuously and synchronously fed into the reaction channel for Michael addition reaction under the synchronous pushing of the syringe pump, the reaction temperature is controlled to be 30-55 DEG C, the reaction time of the reaction solution continuously flowing in the reaction channel is 10-60 min, the reaction solution flowing out of the reaction channel is collected on line through the product collector, and the reaction solution is subjected to post-treatment to obtain vitamin B6 ester shown in formula (III); the concentration ratio of the vitamin B6 solution shown in formula (I) to the fatty acid vinyl ester solution shown in formula (II) is 1:1-5; the addition amount of the catalyst is 0.03 g / mL-0.06 g / mL based on the volume of the reaction solvent within the maximum capacity of the reaction channel for accommodating the filled catalyst.

8. The process for the online synthesis of vitamin B6 esters according to any one of claims 1 to 7, characterized in that: The post-treatment is as follows: the solvent in the reaction solution is removed by evaporation under reduced pressure, a mixed solution of methanol and dichloromethane with a volume ratio of 1:10 is used as an eluent for silica gel column chromatography, the eluent containing the target compound is collected, and vitamin B6 ester shown in formula (III) is obtained by evaporation.

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