CN114249794B - Synthesis method of oxidized glutathione - Google Patents
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Abstract
The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing oxidized glutathione. The invention synthesizes oxidized glutathione by adopting the micro-channel continuous flow reactor, and finally effectively improves the reaction yield and the product purity, eliminates the potential safety hazard, greatly shortens the reaction time, reduces the use of solvents or does not use solvents and reduces three wastes by reasonably controlling the flow rate, the reactant ratio and the reaction time of the reduced glutathione and the oxidant pumped into the integrated micro-channel continuous flow reactor.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing oxidized glutathione.
Background
Glutathione (GSH) is a tripeptide compound that is condensed from L-cysteine, gamma-L-glutamic acid, and glycine. Glutathione has two forms of reduced form (GSH) and oxidized form (GSSH), and the reduced glutathione is taken as the main material, and accounts for more than 98% of the total glutathione. Glutathione is widely distributed in animal, plant and microbial cells, is a natural antioxidant and free radical scavenger, can effectively remove metabolites such as peroxidized lipid in human body, inhibit peroxidized damage of cell lipid, and has physiological effects of delaying aging, resisting oxidation, resisting allergy, etc. Glutathione is mainly applied to the fields of foods, medicines, health products, cosmetics and the like at present, and has wide application prospect in the fields of agricultural fertilizers and feed additives. Glutathione is easily oxidized in the air to generate byproducts, and oxidized glutathione is relatively stable and can be metabolized into glutathione in organisms, so that the glutathione is convenient for long-term storage.
At present, oxidized glutathione is prepared by mainly taking glutathione as a raw material, and diethyl bromomalonate, potassium ferricyanide, hydrogen peroxide and oxygen as oxidizing agents. In industrial production, the factors such as production cost, purification method, safety risk and the like are integrated, and oxygen and hydrogen peroxide are commonly used as oxidizing agents to directly oxidize glutathione.
However, batch production processes based on tank reactors are currently commonly used for the production of oxidized glutathione: the reaction process has low mass transfer and heat transfer efficiency, long feeding time and difficult accurate regulation and control of the reaction process. The following problems are mainly present: 1. when the traditional kettle type reactor takes hydrogen peroxide as an oxidant, the hydrogen peroxide concentration is high in the initial reaction stage, the reaction is rapid, and a large amount of heat is released, so that if the heat exchange is not timely carried out, the system is heated, side reactions and peroxidation are easy to occur, the subsequent purification is influenced, and the product quality is finally influenced; 2. the heat transfer capacity of the kettle type reactor is greatly influenced by the form of equipment, and obvious amplification effect exists, so that the follow-up process optimization and amplification test are required; 3. the traditional kettle type reactor takes the reaction type of oxidizing glutathione by oxygen or compressed air as gas-liquid reaction, namely, oxygen is introduced into the glutathione solution, the reaction time is long, the reaction efficiency is low, the yield of the product is low, and the productivity is limited.
Disclosure of Invention
In view of the above, the invention provides a method for synthesizing oxidized glutathione, which aims at the defects of unstable product quality, long reaction time, low production efficiency, large consumption of oxidant, more side reactions, poor safety, amplification effect and the like in the prior art.
In order to achieve the above object, the present invention provides the following technical solutions:
a method for synthesizing oxidized glutathione comprises the following steps:
50-150 g/L reduced glutathione solution is mixed for 10-80mL min -1 The flow rate of the oxidant is 20-400 mL min -1 Respectively pumping the flow rates into a reaction temperature zone of the integrated micro-channel continuous flow reactor, and carrying out reaction residence for 15-60 s;
and collecting and purifying the reaction liquid to obtain oxidized glutathione.
Preferably, the oxidant is H with the mass fraction of 2-5% 2 O 2 A solution; the flow rate of the oxidant is 20-40 mLmin -1 。
Preferably, the oxidant is oxygen or compressed air; the flow rate of the oxidant is 100-40 mLmin -1 。
Preferably, the purity of the oxygen is 60-90%.
Preferably, the pressure of the compressed air is 0.1-8.0Mpa.
Preferably, the mass-volume ratio of the reducing glutathione to the oxidant is 1:0.5-1:40 in g/ml.
Preferably, the reaction temperature zone comprises a first temperature zone and a second temperature zone; temperature T of the first temperature zone 1 At 25-60 deg.C for a residence time t 1 5 to 30 seconds; temperature T of the second temperature zone 2 At a temperature of 25-60 ℃ and a residence time t 2 Is 5 to 30 seconds.
Preferably, the reaction temperature zone includes:
first temperature zone: a gas-liquid mixing unit;
second temperature zone: an oxidation reaction unit;
third temperature zone: a gas-liquid separation unit;
wherein the temperature T of the first temperature zone 1 At a temperature of 25-60 ℃ and a residence time t 1 5 to 30 seconds;
temperature T of the second temperature zone 2 Is between 25 and 60 ℃,residence time t 3 5 to 30 seconds;
temperature T of the third temperature zone 3 At a temperature of 25-60 ℃ and a residence time t 3 Is 5 to 30 seconds.
Preferably, the purification is: collecting reaction liquid, cooling, slowly dripping absolute ethyl alcohol, preserving heat, stirring, crystallizing and filtering; the filter cake is washed by ethanol, and the filter cake is collected and dried in vacuum.
Preferably, the cooling temperature is 10-25 ℃; the time of heat preservation and stirring is 0.5h-6.0h; the concentration of the ethanol is 70-90%; the temperature of the vacuum drying is 45-60 ℃ and the time is 2-6 h.
The invention synthesizes oxidized glutathione by adopting the micro-channel continuous flow reactor, reasonably controls the flow rate of the reduced glutathione and the oxidant pumped into the integrated micro-channel continuous flow reactor, the reactant ratio and the reaction time, finally effectively improves the reaction yield and the product purity, eliminates the potential safety hazard, greatly shortens the reaction time, reduces the use of solvents or does not use solvents, and reduces three wastes. Compared with the prior art, the method has the following advantages:
(1) The mass and heat transfer efficiency is obviously improved by adopting a micro-channel continuous flow technology, and the amplification is easy;
(2) The reaction time is short, the reaction rate is high, and the conversion rate can be 99% within 30-60 s;
(3) The substrate conversion rate is high and can reach 99% at most, so that the purification and separation are convenient;
(4) The reaction condition is mild, when hydrogen peroxide is used as an oxidant, the reaction can be completed only by using 2% hydrogen peroxide by mass fraction at 30 ℃;
(5) Compressed air can be used as an oxidant, so that the energy consumption is low and no pollution is caused;
(6) In the reaction process, the reaction is carried out under the water solution, no other solvents are needed, and three wastes are less.
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FIG. 1 shows a schematic of a continuous flow microchannel reactor comprising two temperature zones;
figure 2 shows a schematic of the structure of a continuous flow microchannel reactor containing three temperature zones.
Detailed Description
The invention provides a method for synthesizing oxidized glutathione. Those skilled in the art can, with the benefit of this disclosure, suitably modify the process parameters to achieve this. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included in the present invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the relevant art that the invention can be practiced and practiced with modification and alteration and combination of the methods and applications herein without departing from the spirit and scope of the invention.
The invention provides a method for synthesizing oxidized glutathione, which comprises the following steps:
50-150 g/L reduced glutathione solution is mixed for 10-80mL min -1 The flow rate of the oxidant is 20-400 mL min -1 Respectively pumping the flow rates into a reaction temperature zone of the integrated micro-channel continuous flow reactor, and carrying out reaction residence for 15-60 s;
and collecting and purifying the reaction liquid to obtain oxidized glutathione.
According to the invention, the reducing glutathione solution and the oxidant (hydrogen peroxide solution, oxygen or compressed air) are continuously added into the feed inlet of the integrated micro-channel continuous flow reactor, and oxidized glutathione is continuously obtained from the discharge outlet of the integrated continuous flow reactor, wherein the reaction time is equal to or less than 60s. The method is a rapid, safe, efficient, highly universal and easy-to-mass-production continuous flow synthesis process of oxidized glutathione. The integrated continuous flow micro-channel reactor comprises three units: the device comprises a gas-liquid mixing unit, an oxidation reaction unit and a gas-liquid separation unit. Every three units (a gas-liquid mixing unit, an oxidation reaction unit and a gas-liquid separation unit) are provided with at least one heat exchange module, the heat exchange modules are connected with a heat exchanger, raw material reduced glutathione and oxygen or compressed air continuously enter the three units in the microchannel continuous flow reactor for reaction, then a reaction liquid is collected at an outlet of the reactor, and a target product, namely oxidized glutathione, is obtained after purification.
In the preparation method provided by the invention, the reduced glutathione solution
The reduced glutathione solution is treated for 10-80mL min -1 The flow rate of the oxidant is 20-400 mL min -1 Respectively pumped into the reaction temperature zone of the integrated micro-channel continuous flow reactor. Wherein, the mass volume ratio of the reducing glutathione to the oxidant is preferably 1:0.5-1:40 in g/ml, and can be specifically: 1:0.5, 1:5, 1:10, 1:20, or 1:40; the concentration of the reduced glutathione solution can be specifically 100g/L, 50g/L or 150g/L; the flow rate of the reduced glutathione solution is preferably 20-40 mL min -1 Specifically, the concentration of the solution is 20mL min -1 Or 40mL min -1 . Wherein the oxidant is H 2 O 2 When in solution; the H is 2 O 2 The mass fraction of the solution is 2% -5%, and can be specifically 2% or 5%; the H is 2 O 2 The flow rate of the solution is preferably 20-40 mL min -1 . When the oxidant is oxygen, the purity of the oxygen is preferably 60-90%, and can be 60, 70%, 80 or 90%; the flow rate of oxygen is preferably 100-400 mL min -1 Specifically, the concentration of the solution is 100mL min -1 、200mL min -1 、300mL min -1 Or 400mL min -1 The method comprises the steps of carrying out a first treatment on the surface of the When the oxidant is compressed air, the pressure of the compressed air is preferably 0.1-8.0Mpa, specifically 0.1Mpa, 0.2Mpa, 1Mpa, 2Mpa, 5Mpa, 8Mpa; the flow rate of the compressed air is preferably 100-400 mL min -1 Specifically, the concentration of the solution is 100mL min -1 、200mL min -1 、300mL min -1 Or 400mL min -1 . In the invention, the reaction temperature zone of the integrated micro-channel continuous flow reactor comprises two temperature zones (see figure 1), namely a first temperature zone and a second temperature zone; temperature T of the first temperature zone 1 Preferably 25-60 ℃, and in particular can be 25 ℃,30, 40, 50 or 60 ℃; residence time t 1 5 to 30s, specifically 5s, 10s, 15s, 20s or 30s; temperature T of the second temperature zone 2 25-60 ℃, specifically 25 ℃,30, 40, 50 or 60 ℃; residence time t 2 Is 5 to 30s, and can be specifically 5s, 10s, 15s, 20s or 30s.
In the present invention, the reaction temperature zone of the integrated microchannel continuous flow reactor comprises three temperature zones (see fig. 2):
first temperature zone: a gas-liquid mixing unit;
second temperature zone: an oxidation reaction unit;
third temperature zone: a gas-liquid separation unit;
wherein the temperature T of the first temperature zone 1 25-60 ℃, specifically 25 ℃,30, 40, 50 or 60 ℃; specifically, the time interval can be 5s, 10s, 15s, 20s or 30s; residence time t 1 5 to 30s, specifically 5s, 10s, 15s, 20s or 30s;
temperature T of the second temperature zone 2 25-60 ℃, specifically 25 ℃,30, 40, 50 or 60 ℃; specifically, the time interval can be 5s, 10s, 15s, 20s or 30s; residence time t 2 5 to 30s, specifically 5s, 10s, 15s, 20s or 30s;
temperature T of the third temperature zone 3 25-60 ℃, specifically 25 ℃,30, 40, 50 or 60 ℃; residence time t 3 5 to 30 seconds; in particular 5s, 10s, 15s, 20s or 30s.
In the invention, after the reaction is carried out in a reaction temperature zone of a micro-channel continuous flow reactor to obtain a reaction liquid, the reaction liquid is collected and purified to obtain oxidized glutathione. Preferably, the purification is: collecting reaction liquid, cooling, slowly dripping absolute ethyl alcohol, preserving heat, stirring, crystallizing and filtering; the filter cake was washed with 90% ethanol and the filter cake was collected and dried in vacuo. Wherein the cooling temperature is preferably 10-25 ℃, and can be 25 ℃, 20 ℃ or 10 ℃; the time of heat preservation and stirring is preferably 0.5h-6.0h, and can be specifically 0.5h or 6h; the concentration of the ethanol is preferably 70-100%, and can be 70%, 80%, 90% or 100%; the temperature of the vacuum drying is preferably 45-60 ℃, and can be 45 ℃, 50 ℃, 55 ℃ or 60 ℃ in particular; the time of the vacuum drying is preferably 2 to 6 hours, and specifically may be 2 hours, 4 hours or 6 hours.
The continuous flow microreactor can control the chemical reaction field within the scale of hundreds of micrometers, obviously improve the specific surface area in the reaction space, strengthen the heat convection rate, shorten the molecular diffusion time and realize high-efficiency heat and mass transfer. The microchannel continuous flow reactor is made of special glass or special ceramic materials, has excellent corrosion resistance, high temperature resistance and high pressure resistance, and is suitable for various chemical reactions. The unique multilayer structure of the reactor is integrally designed, so that the total heat exchange efficiency and the mass transfer performance of fluid mixing are 100 times higher than those of the traditional stirred tank reactor. The following advantages are provided in a variety of chemical synthesis applications: the method has the advantages of improving the reaction yield and the product purity, eliminating potential safety hazards, greatly shortening the reaction time, reducing the use of solvents or no solvents, and reducing the generation of three wastes.
The invention synthesizes oxidized glutathione by adopting a micro-channel continuous flow reactor, and reasonably controls the concentration of reduced glutathione (10-80 mL min) -1 ) The flow rate, the reactant ratio and the reaction time of the integrated micro-channel continuous flow reactor pumped with the oxidant are finally and effectively improved, the reaction yield and the product purity are finally and effectively improved, the potential safety hazard is eliminated, the reaction time is greatly shortened, the use of solvents is reduced or the solvents are not used, and the three wastes are reduced. Compared with the prior art, the method has the following advantages:
(1) The mass and heat transfer efficiency is obviously improved by adopting a micro-channel continuous flow technology, and the amplification is easy;
(2) The reaction time is short, the reaction rate is high, and the conversion rate can be 99% within 30-60 s;
(3) The substrate conversion rate is high and can reach 99% at most, so that the purification and separation are convenient;
(4) The reaction condition is mild, when hydrogen peroxide is used as an oxidant, the reaction can be completed only by using 2% hydrogen peroxide by mass fraction at 30 ℃;
(5) Compressed air can be used as an oxidant, so that the energy consumption is low and no pollution is caused;
(6) In the reaction process, the reaction is carried out under the water solution, no other solvents are needed, and three wastes are less.
Unless otherwise specified, the test materials adopted in the invention are all common commercial products and can be purchased in the market.
The invention is further illustrated by the following examples:
example 1: preparation of oxidized glutathione by using hydrogen peroxide as oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 100mL H 2 O 2 (mass fraction 2%) at 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 81%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 98.0%.
Example 2 preparation of oxidized glutathione Using Hydrogen peroxide as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 50mL H 2 O 2 (mass fraction 2%) at 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. Filtering with Buchner funnel after crystallization, washing the filter cake with 90% ethanol, and collecting filter cake 45Vacuum drying at the temperature of 4 hours to obtain white solid, and the yield of the product is 75%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 95.5%, and the content of the oxidized glutathione in the product is 93.0%.
Example 3 preparation of oxidized glutathione Using Hydrogen peroxide as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 50mL H 2 O 2 (mass fraction 5%) at 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 78%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.0%, and the content of the oxidized glutathione in the product is 97.0%.
Example 4 preparation of oxidized glutathione Using Hydrogen peroxide as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 20mL min -1 Flow rate of (2) and 100mL H 2 O 2 (mass fraction 2%) at 20mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectivelyT 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 76%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.0%, and the content of the oxidized glutathione in the product is 98.0%.
Example 5 preparation of oxidized glutathione Using Hydrogen peroxide as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 20mL min -1 Flow rate of (2) and 50mL H 2 O 2 (mass fraction 5%) at 20mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 75%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.0%, and the content of the oxidized glutathione in the product is 97.0%.
Example 6: preparation of oxidized glutathione by using hydrogen peroxide as oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 100mL H 2 O 2 (mass fraction 2)In%) to 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝40℃，T 2 =40℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 73%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 95.0%.
Example 7: preparation of oxidized glutathione by using hydrogen peroxide as oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 50mL H 2 O 2 (mass fraction 5%) at 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝15s、t 2 =15 s, residence time in continuous flow reactor for 30s total. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝40℃，T 2 =40℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 74%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 96.0%.
Example 8: preparation of oxidized glutathione by using hydrogen peroxide as oxidant
Will be reduced toGlutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate of (2) and 100mL H 2 O 2 (mass fraction 2%) at 40mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution flows through two temperature areas, and the residence time is t respectively 1 ＝30s、t 2 =30 s, residence time in continuous flow reactor total 60s. The reaction temperature areas are respectively connected with the heat exchanger, and the temperatures of the two temperature areas are respectively T 1 ＝30℃，T 2 =30℃. 200mL of the reaction effluent was added to a three-necked round bottom flask and cooled to 25℃and absolute ethanol (400 mL) was slowly added dropwise thereto, followed by stirring for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 80%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 98.0%.
Example 9 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 The flow rate and oxygen (purity 90%) were measured at 200mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-neck round bottom flask, cooled to 25 ℃, absolute ethanol (400 mL) is slowly added dropwise, and the mixture is stirred for 6 hours for crystallization under heat preservation. Filtering with Buchner funnel after crystallization, washing filter cake with 90% ethanol, collecting filter cake, and vacuum drying at 45deg.CDrying for 4h gave 8.1g of a white solid with a product yield of 81%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 99.0%.
Example 10: preparation of oxidized glutathione by taking air as oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mLmin -1 Is used at a flow rate of 200mLmin with compressed air (pressure 0.2 MPa) -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,1 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 81%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 98.5%.
Example 11: preparation of oxidized glutathione by taking air as oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated with 20mLmin -1 Is used at a flow rate of 200mLmin with compressed air (pressure 1.0 MPa) -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchangerThe temperature of the three units is T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,2 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 75%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.0%, and the content of the oxidized glutathione in the product is 98.5%.
Example 12 preparation of oxidized glutathione Using air as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated with 60mLmin -1 Is used at a flow rate of 100mLmin and compressed air (pressure 2.0 MPa) -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝40℃，T 2 ＝40℃，T 3 =40℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,1 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 80%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 98.6%.
EXAMPLE 13 preparation of oxidized glutathione Using air as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask and stirred at room temperature for 10 minutes, then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). Will beThe reduced glutathione solution was used for 40mL min -1 Is used at a flow rate of 300mLmin and compressed air (pressure 5.0 MPa) -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,1 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 82%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 98.7%.
EXAMPLE 14 preparation of oxidized glutathione Using air as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 60mL min -1 Is used at a flow rate of 200mLmin with compressed air (pressure 8.0 MPa) -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,1 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 78%. The conversion rate of the reduced glutathione is 99.9 by liquid chromatography detectionThe content of oxidized glutathione in the product is 98.5 percent.
EXAMPLE 15 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 The flow rate and oxygen (purity 90%) were measured at 200mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (400 mL,1 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 81%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.9%, and the content of the oxidized glutathione in the product is 99.0%.
EXAMPLE 16 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 20mL min -1 Flow rate and oxygen (80% purity) at 200mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. Reacting a continuous flow100mL of the reactor reaction effluent liquid was added to a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (600 mL,2 h) was slowly added dropwise thereto, and the mixture was stirred for 6 hours under heat preservation to crystallize. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 75%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.0%, and the content of the oxidized glutathione in the product is 98.5%.
EXAMPLE 17 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate and oxygen (80% purity) at 200mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝30s，t 3 =10 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝25℃，T 2 ＝25℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-neck round bottom flask, cooled to 25 ℃, absolute ethyl alcohol (200 mL,3 h) is slowly added dropwise into the flask, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 77%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.5%, and the content of the oxidized glutathione in the product is 98%.
Example 18 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate and oxygen (80% purity) at 200mL min -1 Is pumped into the micro-scaleIn a channel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝30s，t 3 =10 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝40℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-neck round bottom flask, cooled to 25 ℃, and absolute ethanol (1000 mL,6 h) is slowly added dropwise into the mixture, and the mixture is stirred for 6h for crystallization under heat preservation. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 78%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.0%, and the content of the oxidized glutathione in the product is 98%.
EXAMPLE 19 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 60mL min -1 Flow rate and oxygen (purity 90%) at 300mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝10s、t 2 ＝10s，t 3 Retention time in continuous flow reactor for 30s total =10 s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask and cooled to 25 ℃, absolute ethyl alcohol (400 mL,4 h) is slowly added dropwise, and the mixture is stirred for 6 hours for crystallization under heat preservation. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the yield of the product is 72%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.0%, and the content of the oxidized glutathione in the product is 98.1%.
EXAMPLE 20 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate and oxygen (purity 60%) at 300mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝10s、t 2 ＝10s，t 3 =20 s, residence time in continuous flow reactor total 40s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝30℃，T 2 ＝30℃，T 3 =30℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask and cooled to 25 ℃, absolute ethyl alcohol (400 mL,5 h) is slowly added dropwise, and the mixture is stirred for 6 hours for crystallization under heat preservation. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 70%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 97.0%, and the content of the oxidized glutathione in the product is 98.2%.
EXAMPLE 21 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated at 40mL min -1 Flow rate and oxygen (purity 70%) were measured at 200mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝10s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 50s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝50℃，T 2 ＝40℃，T 3 =50℃. 100mL of reaction effluent liquid of the continuous flow reactor is added into a three-mouth round bottom flask, cooled to 25 ℃, absolute ethyl alcohol (200 mL,0.5 h) is slowly added dropwise into the flask, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 76%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.5%, and the content of the oxidized glutathione in the product is 98.2%.
EXAMPLE 22 preparation of oxidized glutathione Using air as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated with 80mL min -1 Flow rate and oxygen (purity 90%) at 400mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝20s、t 2 ＝20s，t 3 =20 s, residence time in continuous flow reactor total 60s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝60℃，T 2 ＝40℃，T 3 =40℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask and cooled to 25 ℃, absolute ethanol (400 mL,2 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 74%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.8%, and the content of the oxidized glutathione in the product is 98.6%.
EXAMPLE 23 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution was treated for 10mL min -1 Flow rate and oxygen (purity 90%) at 100mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝5s、t 2 ＝5s，t 3 =5 s, residence time in continuous flow reactor total 15s. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝60℃，T 2 ＝50℃，T 3 =50℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask, cooled to 25 ℃, and absolute ethanol (400 mL,3 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 83%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 99.5%, and the content of the oxidized glutathione in the product is 98.8%.
EXAMPLE 24 preparation of oxidized glutathione Using oxygen as an oxidant
Reduced glutathione (10 g,32.5 mmol) and deionized water (100 mL) were added to a three-necked round bottom flask, stirred at room temperature for 10 minutes, and then the pH of the solution was slowly adjusted to 8.0 using NaOH (2M). The reduced glutathione solution is treated for 50mL min -1 Flow rate and oxygen (purity 90%) at 300mL min -1 Is pumped into the microchannel continuous flow reactor. The reaction solution sequentially passes through three units, and the residence time is t respectively 1 ＝15s、t 2 ＝15s，t 3 =15 s, the residence time in the continuous flow reactor was 45s total. Three units are respectively connected with the heat exchanger, and the temperatures of the three units are respectively T 1 ＝50℃，T 2 ＝50℃，T 3 =50℃. 100mL of the reaction effluent liquid of the continuous flow reactor is added into a three-necked round bottom flask and cooled to 25 ℃, absolute ethanol (400 mL,2 h) is slowly added dropwise thereto, and the mixture is stirred for 6 hours under heat preservation for crystallization. After crystallization, the mixture is filtered by using a Buchner funnel, a filter cake is washed by using 90% ethanol, and the filter cake is collected and dried for 4 hours at 45 ℃ in vacuum to obtain white solid, and the product yield is 85%. The liquid chromatography detection shows that the conversion rate of the reduced glutathione is 98.5%, and the content of the oxidized glutathione in the product is 98.2%.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. The method for synthesizing oxidized glutathione is characterized by comprising the following steps:
50-150 g/L reduced glutathione solution is mixed for 10-80mL min -1 The flow rate of the oxidant is 20-400 mL min -1 Respectively pumping the flow rates into a reaction temperature zone of the integrated micro-channel continuous flow reactor, and carrying out reaction residence for 15-60 s;
and collecting and purifying the reaction liquid to obtain oxidized glutathione.
2. The synthesis method according to claim 1, wherein the oxidant is 2-5% by mass of H 2 O 2 A solution; the flow rate of the oxidant is 20-40 mL min -1 。
3. The synthetic method of claim 1 wherein the oxidant is oxygen or compressed air; the flow rate of the oxidant is 100-400 mL min -1 。
4. A synthetic method according to claim 3, characterized in that the purity of the oxygen is 60-90%.
5. A synthesis method according to claim 3, wherein the pressure of the compressed air is 0.1-8.0Mpa.
6. The synthetic method according to claim 1, wherein the mass to volume ratio of reduced glutathione to oxidant is 1:0.5-1:40 in g/ml.
7. The synthetic method of claim 1 wherein the reaction temperature zone comprises a first temperature zone and a second temperature zone; temperature T of the first temperature zone 1 At 25-60 deg.C for a residence time t 1 5 to 30 seconds; temperature of the second temperature zoneT 2 At a temperature of 25-60 ℃ and a residence time t 2 Is 5 to 30 seconds.
8. The method of synthesis according to claim 1, wherein the reaction temperature zone comprises:
first temperature zone: a gas-liquid mixing unit;
second temperature zone: an oxidation reaction unit;
third temperature zone: a gas-liquid separation unit;
wherein the temperature T of the first temperature zone 1 At a temperature of 25-60 ℃ and a residence time t 1 5 to 30 seconds;
temperature T of the second temperature zone 2 At a temperature of 25-60 ℃ and a residence time t 2 5 to 30 seconds;
temperature T of the third temperature zone 3 At a temperature of 25-60 ℃ and a residence time t 3 Is 5 to 30 seconds.
9. The synthetic method of claim 1 wherein the purifying is: collecting reaction liquid, cooling, slowly dripping absolute ethyl alcohol, preserving heat, stirring, crystallizing and filtering; the filter cake is washed by ethanol, and the filter cake is collected and dried in vacuum.
10. The synthetic method of claim 9 wherein the cooled temperature is 10-25 ℃; the time of heat preservation and stirring is 0.5h-6.0h; the concentration of the ethanol is 70-100%; the temperature of the vacuum drying is 45-60 ℃ and the time is 2-6 h.
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