CN111875569B - Method for catalytic conversion of salvianolic acid B by using natural eutectic solvent - Google Patents
Method for catalytic conversion of salvianolic acid B by using natural eutectic solvent Download PDFInfo
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Abstract
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a method for preparing other salvianolic acid compounds by using a natural eutectic solvent as a solvent and a catalyst to catalyze and convert salvianolic acid B. The method uses natural eutectic solvent (NaDES) as solvent and catalyst, and converts salvianolic acid B rich in Saviae Miltiorrhizae radix into active components with low content in natural Saviae Miltiorrhizae radix such as salvianolic acid A, lithospermic acid, salvianic acid A, protocatechuic aldehyde, etc. The method mainly comprises the following steps: (1) Pulverizing Saviae Miltiorrhizae radix rhizome, adding water, extracting with ultrasonic assistance, and separating and purifying salvianolic acid B with macroporous resin; (2) Adding salvianolic acid B with purity higher than 90% into NaDES water solution with different compositions, heating to catalyze salvianolic acid B as active ingredient mixture, and separating the mixture by column chromatography to obtain active ingredients such as salvianolic acid A, lithospermic acid, salvianic acid A, protocatechuic aldehyde, etc. The method has the advantages of simple operation, high conversion rate, environment friendliness and the like, and is expected to be used for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a method for preparing other salvianolic acid compounds by using natural eutectic solvent as a solvent and a catalyst to catalyze and convert salvianolic acid B.
Background
The red sage root (Salvia miltiorrhiza Bunge) is a widely used Chinese medicinal material, has certain curative effects on cerebrovascular diseases, metabolic disorders, hepatitis and cancers, and has been widely accepted in clinical curative effects. The main active ingredient of the red sage root is salvianolic acid compound, wherein the content of salvianolic acid B is highest. Other salvianolic acids such as salvianolic acid A, lithospermic acid, salvianic acid A, and protocatechuic aldehyde have very low content. Studies have shown that salvianolic acid A has excellent biological activities such as antioxidation, free radical scavenging, neuroprotection, prevention and treatment of cardiovascular diseases, and the like, and is superior to salvianolic acid B in some aspects. The salvianolic acid A can obviously improve the myocardial ischemia range of dogs of experimental animals, obviously inhibit serum lactate dehydrogenase LDH and creatine kinase CK from being increased caused by myocardial infarction no matter in vein or oral administration (Li Lei, ren Jianxun, lin Zhirong, shi Yue, ma Yanlei, liu Jianxun. The influence of different administration routes of the salvianolic acid A on the acute myocardial ischemia of dogs [ J ]. J. Chinese journal of traditional Chinese medicine, 2016,41 (05): 910-916.). Wang Haigang by using a model of platelet aggregation induced by adenosine diphosphate, arachidonic acid and thrombin, it has been found that salvianolic acid A has not only an overall mild inhibitory effect on platelet aggregation but also a remarkable protective effect on cerebral ischemia caused by thrombus as compared with aspirin (Wang Haigang, kong Linglei, wang Rui, chen Yanxia, yang Shilun, zhao Xiaoyue, zhou Qimeng, du Guanhua. Comparative study of antithrombotic effect of salvianolic acid A with aspirin [ J ]. Pharmaceutical journal, 2019,54 (02): 301-307.). Wang Shoubao and the like find that when the administration dose of salvianolic acid A is 5 and 10mg/kg, the administration dose is more effective than 10mg/kg of salvianolic acid B by using a rat myocardial ischemia model, and further find that when the administration dose of salvianolic acid A is 2.5mg/kg, the treatment effect is equivalent to 10mg/kg of salvianolic acid B. (Wang S B, tian S, yang F, et al, cardioguard effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rates. Eur J Pharm,2009, 615:125).
However, the research on the chemical components of the red sage root medicinal material shows that: the main component of the red sage root is salvianolic acid B, and other salvianolic acids such as salvianic acid A, protocatechuic aldehyde, lithospermic acid and salvianolic acid A have extremely low content and cannot be directly extracted to obtain the salvianolic acid compounds. There are some technical approaches to attempt to convert salvianolic acid B into salvianolic acid a by chemical reaction, for example: through high temperature and high pressure and adjusting the pH of the solvent, salvianolic acid B can be converted into other salvianolic acid compounds, such as salvianolic acid B generates a large amount of salvianolic acid A at pH value of 1, and generates a large amount of salvianic acid A at pH value of 12 (Xia H, sun L, lou H, rahman M.Convergence of salvianolic acid B into salvianolic acid A in tissues of Radix Salviae Miltiorrhizae using high temperature, high pressure and high sensitivity. Phytometricine, 2014,21,906-911). The Chinese patent with the application number of CN201310487751.6 discloses a preparation method of salvianolic acid A, which comprises the steps of adding an extractant into a medicinal material of red sage root, heating and extracting, and filtering and concentrating the extract to obtain the extract of the red sage root; regulating pH of Saviae Miltiorrhizae radix extract to 4-8, concentrating under reduced pressure, and heating the concentrated solution at 70-100deg.C for 5-40 hr to obtain salvianolic acid A crude product solution; the method can obtain a certain amount of pure salvianolic acid A, but has the obvious defects of long reaction time, need to repeatedly adjust the pH value and the like. Another preparation method of salvianolic acid a is disclosed in chinese patent application No. CN201610806533.8, wherein salvianolic acid B is prepared into 35-45mg/mL solution with NaOH or NaHCO3 water having pH of 3.5-4.5, and the solution is placed in a subcritical water reaction kettle, after the heating furnace reaches 170-190 ℃ and is stabilized, the reaction kettle is placed in the heating furnace, after 50-70 min, the reaction kettle is taken out and is placed in an ice water bath or a cold water bath for cooling, the liquid is taken out, and freeze-drying is performed to obtain a salvianolic acid a crude product, and then the salvianolic acid a crude product is separated and purified by utilizing high-efficiency countercurrent chromatography to obtain salvianolic acid a with purity of more than 98%, wherein the method has obvious disadvantages, such as the need of adjusting pH value, high pressure resistant equipment, and the higher temperature also increases the consumption of energy. In addition, the patent with the application number of CN201310192210.0 discloses the conversion of the red sage root extracting solution by using high boiling point organic solvents such as glycol, dimethyl sulfoxide and dimethylformamide, and the conversion of the salvianolic acid B under normal pressure is realized, but a large amount of organic solvents are used to increase the process components and have high toxicity.
Besides the problems, the reaction efficiency is low, the products are complex and the like in the salvianolic acid B conversion experiment, and a great deal of patents at present only make adjustment on the aspects of adjusting the pH value, changing the reaction temperature and changing the reaction solvent or additives, but no deep new method appears, and the Chinese patent application No. CN201210487598.2 discloses that ferric chloride, ruthenium trichloride, zinc chloride, palladium chloride and the like are used as catalysts for catalytic conversion of the salvianolic acid B, and the catalytic effects of the catalysts are not obviously different except that most of the catalysts are expensive. Although the method improves the efficiency of converting the salvianolic acid B into the salvianolic acid A, the conversion rate of the salvianolic acid B is only about 63 percent, and the yield of the salvianolic acid A is about 42 percent. The patent with the application number of CN201410200983.3 considers that in the process of converting the salvianolic acid A, air is isolated, so that the salvianolic acid B is prevented from being damaged to the greatest extent, and further, the salvianolic acid A is converted into the salvianolic acid A as much as possible, and the generated salvianolic acid A is prevented from being damaged by oxidation. Therefore, nitrogen or argon is used as a protective gas to react under the condition of air isolation, and the best experimental result is as follows: concentrating the extract to 400mL, placing in a high-pressure reaction kettle, reacting for 2h at 135 ℃ under the protection of nitrogen and 0.31M protocatechuic aldehyde, and stopping the reaction. The content of salvianolic acid B in the extract is measured to be 0.95%, the content of salvianolic acid A in the conversion solution is measured to be 0.47%, and the conversion rate is measured to be 71.9%. Although the above method improves the conversion rate to about 72%, the participation of nitrogen or argon not only greatly increases the cost, but also eliminates the complicated operation of air and requires expensive sealing equipment, which is disadvantageous for large-scale industrial production.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provides a method for selectively preparing other salvianolic acid compounds by taking salvianolic acid B as a raw material by using a natural eutectic solvent as a solvent and a catalyst in a green and efficient way.
In order to achieve the above object, the present invention provides the following technical solutions:
a method for catalytically converting salvianolic acid B by using natural eutectic solvent comprises the following steps of:
(1) Extracting salvianolic acid B: extracting Saviae Miltiorrhizae radix with water as solvent under heating and ultrasound, filtering and centrifuging the extractive solution, collecting supernatant, distilling under reduced pressure to obtain paste, and separating and purifying with macroporous resin to obtain salvianolic acid B;
(2) Synthetic natural eutectic solvents: mixing hydrogen bond donor HBD with hydrogen bond acceptor HBA and/or deionized water in a certain proportion, heating and stirring to obtain transparent clear solution, namely natural eutectic solvent;
(3) Catalytic conversion of salvianolic acid B: adding salvianolic acid B into the eutectic solvent, and heating and reacting for a certain time to obtain salvianolic acid B conversion solution;
(4) And (3) separating and purifying: and (3) carrying out column chromatography separation and purification on the salvianolic acid B conversion solution in the step (3) to obtain the salvianolic acid compound with the purification degree reaching 95%.
Preferably, the specific operation of extracting the salvianolic acid B in the step (1) is as follows: adding water into radix Salviae Miltiorrhizae powder, ultrasonic extracting at 50deg.C for 2 hr, filtering with gauze to obtain extractive solution, centrifuging at 7000G for 10min, collecting supernatant, adding water into residue, repeatedly performing ultrasonic treatment, extracting for 3 times, mixing the supernatants, concentrating at 50deg.C to obtain paste, separating and purifying the paste with AB-8 macroporous resin column chromatography, eluting with water and 75% ethanol, collecting 75% ethanol eluate, and spin-drying at 50deg.C to obtain salvianolic acid B.
Preferably, the hydrogen bond donor in the step (2) includes: glycerol (Gly), lactic acid (Lac), urea (Ur); the hydrogen bond acceptors include: choline chloride (ChCl), betaine (Bet), L-proline (L-Pro).
Preferably, the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor in the step (2) is 1:1-2.
Preferably, the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor to the deionized water in the step (2) is 1:1-2:1-5.
Preferably, the heating temperature in the step (2) is 80-100 ℃, and the stirring time is 0.5-2h; more preferably, the temperature is 80℃and the time is 1h.
Preferably, the volume fraction of the eutectic solvent in the step (3) is 75% -100%.
Preferably, the feeding amount of the salvianolic acid B in the step (3) is 2mg/mL of the eutectic solvent.
Preferably, the reaction temperature in the step (3) is 80-140 ℃ and the reaction time is 2-48h.
Preferably, the specific steps of separation and purification in the step (4) are as follows: extracting salvianolic acid B conversion liquid with ethyl acetate, steaming the organic phase, separating and purifying the product by column chromatography, wherein the eluent is petroleum ether, ethyl acetate and methanol.
Preferably, the salvianolic acid compound is salvianolic acid A, lithospermic acid, salvianic acid A and protocatechuic aldehyde, and the reaction conditions for converting salvianolic acid B into various substances are as follows:
a. reaction conditions for converting salvianolic acid B into salvianolic acid A: betaine (Bet) -lactic acid (Lac) -deionized water (molar ratio 1:1:1) with volume fraction of 75% is eutectic solvent, and the reaction is carried out for 6 hours at 120 ℃ to obtain the salvianolic acid B with the conversion rate of 89.8% and the salvianolic acid A with the generation rate of 72.4%;
b. reaction conditions for converting salvianolic acid B into lithospermic acid: betaine (Bet) -lactic acid (Lac) -deionized water (molar ratio 1:1:1) with volume fraction of 75% is eutectic solvent, and the reaction is carried out at 80deg.C for 36h to obtain salvianolic acid B with conversion rate of 67.6% and lithospermic acid generation rate of 31.9%;
c. reaction conditions for converting salvianolic acid B into salvianic acid A and protocatechuic aldehyde: betaine (Bet) -urea (Ur) -deionized water (molar ratio 1:1:2) with a volume fraction of 75% is used as a eutectic solvent, and the reaction is carried out for 2 hours at 140 ℃, the salvianolic acid B is completely converted, and the yields of salvianic acid A and protocatechuic aldehyde are respectively 0.77 and 0.56mol/mol SAB (based on the amount of the substances relative to the salvianolic acid B).
According to the method for catalytically converting salvianolic acid B by using the natural eutectic solvent, disclosed by the invention, the selectivity of the salvianolic acid B conversion can be realized by selecting different natural eutectic solvents:
(1) Taking 75% betaine (Bet) -lactic acid (Lac) as a eutectic solvent, reacting for 6 hours at 120 ℃, wherein the conversion rate of salvianolic acid B is 89.8%, and the generation rate of salvianolic acid A is 72.4%;
(2) Reacting 75% betaine (Bet) -lactic acid (Lac) as eutectic solvent at 80deg.C for 48 hr to obtain salvianolic acid B with conversion rate of 71.4%, and generating lithospermic acid (29.0% yield) and salvianolic acid A (31.9% yield);
(3) Taking 75% betaine (Bet) -urea (Ur) as a eutectic solvent, and reacting for 2 hours at 140 ℃ to fully convert salvianolic acid B to generate a large amount of salvianic acid A (0.77 mol/mol SAB) and protocatechuic aldehyde (0.56 mol/mol SAB).
Compared with the prior art, the invention has the beneficial effects that: the invention provides a method for efficiently, environmentally-friendly and simply converting salvianolic acid B into active ingredients with lower content in salvianolic acid A, lithospermic acid, tanshinol, protocatechuic aldehyde and other red sage root by using a eutectic solvent, wherein the method selectively prepares various salvianolic acid compounds with lower natural content by introducing a natural eutectic solvent (Natural Deep Eutectic Solvent, naDES) as a solvent and a catalyst, wherein the conversion rate of the salvianolic acid B reaches 89.8-100%, and the generation rate of the salvianolic acid A also reaches 72.44%. Compared with the prior reported method, the method can be carried out under normal pressure, does not need to repeatedly adjust the pH value, does not have the defect of inflammability and explosiveness of the organic solvent, has high conversion efficiency, is different along with different products of the natural eutectic solvent type, has the advantages of greenness, high efficiency, simple operation, safety and the like, and is very suitable for industrial production. The experiment introduces the natural eutectic solvent into the preparation of the traditional Chinese medicine components, and provides a new research and development idea for the reaction preparation of the traditional Chinese medicine components.
Drawings
FIG. 1 is a high performance liquid chromatogram of extracting purified salvianolic acid B;
FIG. 2 is a high performance liquid chromatogram of betaine-lactic acid catalytic conversion of salvianolic acid B to salvianolic acid A (4 mg salvianolic acid B/2mL 75% DES-1, 120deg.C, 2 h);
FIG. 3 is a high performance liquid chromatogram of betaine-lactic acid catalytic conversion of salvianolic acid B to lithospermic acid, salvianolic acid A (4 mg salvianolic acid B/2mL 75% DES-1, 80 ℃ C., 36 h);
FIG. 4 is a high performance liquid chromatogram of betaine-urea catalytic conversion of salvianolic acid B to salvianic acid A and protocatechuic aldehyde (4 mg salvianolic acid B/2mL 75% DES-2, 120deg.C, 2 h);
FIG. 5 is a control HPLC chromatogram of water-heated converted salvianolic acid B (120deg.C, 2 h).
Detailed Description
The following embodiments are provided to further illustrate the technical solution of the present invention by way of specific examples, and in conjunction with the accompanying drawings, so as to help those skilled in the art to understand the inventive concept, technical solution of the present invention more completely, accurately and deeply, but it should be noted that the scope of the present invention is not limited thereto.
EXAMPLE 1 catalytic conversion of salvianolic acid B to salvianolic acid A with betaine-lactic acid as solvent and catalyst
Pouring 250G of powder of radix Salviae Miltiorrhizae (Yunnan) into a 2L beaker, adding 1L of deionized water, ultrasonically extracting at 50deg.C for 2 hours, filtering with gauze to obtain extractive solution, centrifuging at 7000G for 10min, collecting supernatant, adding 1L of deionized water into the extractive residue, extracting for 3 times, mixing extractive solutions, and concentrating the supernatant at 50deg.C to obtain oily paste. A chromatographic column (3 cm. Times.30 cm) was prepared, the column (3 cm. Times.30 cm) was packed with AB-8 macroporous resin soaked in methanol, rinsed with a large amount of deionized water until no methanol smell and clear, and the concentrated paste was applied to the column until the whole AB-8 macroporous resin column was covered with oily paste (about 20 mL), overnight, and the elution procedure was as follows: the column was flushed with 2L deionized water until the eluate color was clear, eluting with 300mL 25% ethanol, 500mL 75% ethanol, 300mL 100% ethanol in that order. Collecting 75% ethanol eluent, spin-drying at 50deg.C, and separating by AB-8 macroporous resin column chromatography to obtain 4g total self-made salvianolic acid B with purity greater than 90%;
5.00g betaine, 3.84g lactic acid and 0.77g water were mixed in a molar ratio of 1:1:1, and heated and stirred at 80℃for 1 hour to form a clear and uniform eutectic solvent. 1.5mL of betaine-lactic acid natural eutectic solvent is mixed with 0.5mL of water to obtain 2mL of 75% betaine-lactic acid natural eutectic solvent, the solution is added into a 25mL round bottom flask, 4mg of salvianolic acid B (self-made) is accurately weighed, and the mixture is heated at 120 ℃ for 6 hours. Obtaining salvianolic acid A mixed solution converted by salvianolic acid B, fixing the volume of the mixed solution to 10mL by using water, taking a proper amount of sample, centrifuging for 10min at 16200 Xg, taking supernatant, detecting by High Performance Liquid Chromatography (HPLC), obtaining the types and the contents of compounds contained in the salvianolic acid B converted solution according to standard curves of the compounds (salvianolic acid B and salvianolic acid A), and calculating the salvianolic acid B conversion rate and the salvianolic acid A generation rate. The conversion rate of salvianolic acid B is 89.8%, and the generation rate of salvianolic acid A is 72.4%. After the reaction was completed, 15mL of deionized water was added to the system and mixed well, extracted 3 times with 15mL of ethyl acetate, and the ethyl acetate phases were combined and concentrated. Taking a proper amount of concentrated organic phase sample, purifying by conventional chromatographic means such as silica gel, sephadex LH-20 and the like to obtain powdery crystals, wherein the purity of the product salvianolic acid A is more than 95%.
EXAMPLE 2 catalytic conversion of Salvianolic acid B to lithospermic acid, salvianolic acid A with betaine-lactic acid as solvent and catalyst
The reaction temperature and reaction time after adding salvianolic acid B in example 1 were changed to 80℃for 48 hours, and the other parts were the same as in example 1, to obtain a salvianolic acid B conversion of 71.4%, a lithospermic acid production rate of 29.0%, and a salvianolic acid A production rate of 31.9%.
EXAMPLE 3 catalytic conversion of salvianolic acid B to salvianic acid A, protocatechuic aldehyde with betaine-Urea as solvent and catalyst
The natural eutectic solvent in example 1 was changed from betaine-lactic acid to 5g betaine, 2.56g urea, and 1.54g water in a molar ratio of 1:1:2, and the mixture was heated and stirred at 100℃for 2 hours to form a clear and uniform eutectic solvent. 1.5mL of betaine-urea natural eutectic solvent is mixed with 0.5mL of water to obtain 2mL of 75% betaine-urea natural eutectic solvent, the solution is added into a 25mL round bottom flask, 4mg of salvianolic acid B (self-made) is accurately weighed, and the solution is heated at 140 ℃ for 2 hours. Other operations are the same, the conversion rate of salvianolic acid B is more than 99%, and 0.77mg/mg SAB of salvianic acid A is obtained, and 0.56mg/mg SAB of protocatechuic aldehyde is obtained.
Example 4 Effect of eutectic solvent species on the catalytic conversion of salvianolic acid B
The procedure of example 1 was changed to the one described in Table 1, the composition of which was hydrogen bond acceptor, hydrogen bond donor and/or deionized water, 4mg of salvianolic acid B was added to 2mL of 75% eutectic solvent, the temperature and reaction time were 120℃and 2 hours, respectively, and the other procedures were the same as in example 1, and the conversion rate of salvianolic acid B, the production rate of salvianolic acid A and the yields of salvianic acid A and protocatechuic aldehyde in the obtained salvianolic acid B conversion solution were as shown in Table 1, and the results showed that the comprehensive catalytic conversion effects of DES-1 and DES-2 were optimal.
TABLE 1 investigation of the catalytic conversion relationship of the eutectic solvent species and salvianolic acid B
Example 5 Effect of volume concentration of eutectic solvent in aqueous solution of eutectic solvent on catalytic conversion Effect
The DES-1 volume concentration in the example 1 is changed to be shown in the table 2, the reaction temperature and the reaction time are changed to 120 ℃ for 2 hours, other operations are the same as those in the example 1, the conversion rate of the obtained salvianolic acid B and the generation rate of the salvianolic acid A are shown in the table 2, the result shows that the catalytic conversion effect of 100% DES-1 is the best, and the difference between the two is not great, and 75% DES-1 is preferred for saving the cost and reducing the operation difficulty.
TABLE 2 influence of eutectic solvent concentration on the catalytic conversion of salvianolic acid B
Example 6 influence of the reaction temperature in the aqueous solution of the eutectic solvent on the catalytic conversion effect
The reaction temperature in example 1 is changed to be shown in Table 2, the reaction time is changed to be 4 hours, and other operations are the same as those in example 1, the conversion rate of the obtained salvianolic acid B and the generation rate of the salvianolic acid A are shown in Table 2, and the result shows that the DES-1 catalytic conversion effect is optimal at 120 ℃.
TABLE 3 influence of temperature on the catalytic conversion of salvianolic acid B
Example 7 Effect of reaction time in aqueous eutectic solvent solution on catalytic conversion Effect
The reaction time in example 1 was changed to that shown in Table 2, and the other operations were the same as in example 1, and the obtained conversion rate of salvianolic acid B and the yield of salvianolic acid A were shown in Table 2, and the results showed that the yield of salvianolic acid A was highest at 120℃for 6 hours.
TABLE 4 influence of reaction time on the catalytic conversion of salvianolic acid B
Comparative example 1 conversion of salvianolic acid B with Water as solvent
The betaine-lactic acid in example 1 was changed to water as a reaction solvent, the reaction temperature and time were changed to 120℃for 2 hours, and the other operations were as in example 1. The conversion rate of salvianolic acid B is 17.51%, the generation rate of salvianolic acid A is less than 12%, and the high performance liquid chromatogram is shown in figure 5. From the comparison result, when the solvent is water, the conversion rate of the salvianolic acid B is extremely low under the same condition, and when the solvent is the eutectic solvent, the salvianolic acid B can be selectively converted into other salvianolic acid compounds with high conversion rate under the same condition.
The above-described embodiments are only preferred embodiments of the present invention, and are not intended to limit the invention in any way, but other variations and modifications are possible without exceeding the technical solutions described in the claims.
Claims (9)
1. A method for catalytic conversion of salvianolic acid B by using natural eutectic solvent is characterized in that the method takes the natural eutectic solvent as solvent and catalyst, and the salvianolic acid B is catalytically converted into other salvianolic acid compounds at normal pressure, and the specific method comprises the following steps:
(1) Extracting salvianolic acid B: extracting Saviae Miltiorrhizae radix with water as solvent under heating and ultrasound, and separating and purifying with macroporous resin to obtain salvianolic acid B;
(2) Preparing a natural eutectic solvent: mixing a hydrogen bond donor with a hydrogen bond acceptor and/or deionized water in a certain proportion, and heating and stirring to prepare a natural eutectic solvent;
(3) Catalytic conversion of salvianolic acid B: adding salvianolic acid B into natural eutectic solvent, and heating to react for a certain time to obtain salvianolic acid B conversion solution;
(4) And (3) separating and purifying: carrying out column chromatography separation and purification on the salvianolic acid B conversion solution obtained in the step (3) to obtain salvianolic acid compounds;
wherein: the hydrogen bond donor in the step (2) is as follows: glycerol, lactic acid, urea; the hydrogen bond acceptors are: choline chloride, betaine, L-proline;
the salvianolic acid compound is at least one of salvianolic acid A, lithospermic acid, salvianic acid A and protocatechuic aldehyde.
2. The method of claim 1, wherein the molar ratio of hydrogen bond donor to hydrogen bond acceptor in step (2) is 1:1-2.
3. The method of claim 1, wherein the molar ratio of hydrogen bond donor, hydrogen bond acceptor and deionized water in step (2) is 1:1-2:1-5.
4. The method for catalytic conversion of salvianolic acid B using natural eutectic solvent according to claim 1, wherein the heating temperature in the step (2) is 80-100 ℃ and the stirring time is 0.5-2h.
5. The method for catalytic conversion of salvianolic acid B using natural eutectic solvent according to claim 1, wherein the heating temperature in the step (2) is 80 ℃ and the stirring time is 1h.
6. The method of claim 1, wherein the volume fraction of the eutectic solvent in the step (3) is 75% -100%.
7. The method for catalytic conversion of salvianolic acid B using natural eutectic solvent according to claim 1, wherein the amount of salvianolic acid B fed in the step (3) is 2mg/mL of eutectic solvent.
8. The method for catalytic conversion of salvianolic acid B using natural eutectic solvent according to claim 1, wherein the reaction temperature in the step (3) is 80-140 ℃ and the reaction time is 2-48h.
9. The method for catalytic conversion of salvianolic acid B using natural eutectic solvent according to claim 1, wherein the salvianolic acid compound is salvianolic acid a, lithospermic acid, salvianic acid a, protocatechuic aldehyde, and the reaction conditions for converting salvianolic acid B into various substances are as follows:
a. reaction conditions for converting salvianolic acid B into salvianolic acid A: a betaine-lactic acid eutectic solvent containing 25 percent of water (volume fraction), and reacting for 6 hours at 120 ℃;
b. reaction conditions for converting salvianolic acid B into lithospermic acid: a betaine-lactic acid eutectic solvent containing 25 percent of water (volume fraction), and reacting for 36 hours at 80 ℃;
c. reaction conditions for converting salvianolic acid B into salvianic acid A and protocatechuic aldehyde: betaine-urea eutectic solvent containing 25% (volume fraction) of water is reacted for 2 hours at 140 ℃.
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| CN102212004A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Method for preparing salvianolic acid A by catalytically converting salvianolic acid B |
| CN110240580A (en) * | 2019-05-16 | 2019-09-17 | 浙江中医药大学 | A method of Salvia root P.E is prepared using eutectic solvent |
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| CN102212004A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Method for preparing salvianolic acid A by catalytically converting salvianolic acid B |
| CN110240580A (en) * | 2019-05-16 | 2019-09-17 | 浙江中医药大学 | A method of Salvia root P.E is prepared using eutectic solvent |
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| Improved stability of salvianolic acid B from Radix Salviae miltiorrhizae in deep eutectic solvents;Jue Chen等;《Anal. Methods》;20160217;第8卷;2502-2509 * |
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