CN108997379B - Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof - Google Patents
Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof Download PDFInfo
- Publication number
- CN108997379B CN108997379B CN201810649370.6A CN201810649370A CN108997379B CN 108997379 B CN108997379 B CN 108997379B CN 201810649370 A CN201810649370 A CN 201810649370A CN 108997379 B CN108997379 B CN 108997379B
- Authority
- CN
- China
- Prior art keywords
- bergenin
- derivative
- sulfur
- reaction
- antioxidant activity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/12—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing sulfur and oxygen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
A sulfur-containing bergenin derivative with antioxidative activity and its synthesis method are disclosed, which comprises reacting bergenin and thiodipropionic acid in organic solvent under the action of dehydrating agent, and after the reaction, purifying the crude product by macroporous resin adsorption to obtain refined product of sulfur-containing bergenin derivative. The reaction conditions are mild, the reaction steps are few, the pollution in the reaction process is small, and the method is suitable for industrial production. The antioxidant experiment result shows that the compound has excellent antioxidant activity and can be used as a novel antioxidant to be deeply developed and applied in the fields of food, medicine and health care products.
Description
Technical Field
The invention relates to the field of medical chemistry, in particular to a sulfur-containing bergenin derivative with antioxidant activity and a synthesis method thereof.
Background
Bergenin, also known as bidens, was originally recorded in the famous plant chessman examination. Is lactone formed by methyl gallic acid C-glucoside, generally white loose needle crystal or crystalline powder, and its plant source is mainly distributed in Yunnan, Sichuan and Tibet provinces. A large number of clinical tests also prove that the bergenin has the functions of diminishing inflammation, easing pain, relieving cough and relieving asthma, is usually used as an effective component of cough-relieving and anti-inflammatory drugs for treating cough, acute and chronic tracheitis, duodenal ulcer and other diseases clinically, and the bergenin tablets are used as a patent drug for treating chronic bronchitis at present. A plurality of recent pharmacological experiments show that the bergenin also has the capabilities of protecting liver, resisting ulcer, improving immunity and resisting lipid oxidation and free radical removal, and experiments show that the bergenin can effectively inhibit lipid peroxidation stress reaction generated in brain tissues after ischemia by inhibiting the increase of the content of lipid peroxidation products in the brain tissues of mice caused by ischemia/reperfusion injury. Meanwhile, the active compound also has an obvious scavenging effect on superoxide anion free radicals generated by a xanthine-xanthine oxidase system, and Maduka and the like believe that bergenin has an anti-lipid oxidation effect through research, so that the active compound can be used as a novel food additive for production of vegetable oil, and the effect of prolonging the shelf life of the vegetable oil is achieved.
Thiodiacetic acid (cas number: 123-93-3) is a common antioxidant and is industrially used for producing thioester antioxidants. More and more studies show that anti-oxidation is an important step in preventing aging because free radicals or oxidants break down cells and tissues, affecting metabolic functions, thereby causing various health problems. If the excess oxidative free radicals can be eliminated, many diseases caused by free radicals and related to aging can be prevented. Therefore, a writer carries out structural modification on bergenin by utilizing thiodiacetic acid to obtain a sulfur-containing bergenin derivative, and verifies the antioxidant activity of the compound by explaining the synthetic method of the compound and combining a preliminary antioxidant experiment on the compound, so as to provide a novel antioxidant additive applied to the fields of foods, medicines and health care products.
Disclosure of Invention
The invention aims to provide a sulfur-containing bergenin derivative with antioxidant activity and a synthesis method thereof, and the sulfur-containing bergenin derivative is mild in reaction conditions, less in reaction steps, less in pollution in the reaction process and suitable for industrial production. The antioxidant experiment result shows that the compound has excellent antioxidant activity and can be used as a novel antioxidant to be deeply developed and applied in the fields of food, medicine and health care products.
The structural formula of the compound is shown as the formula I:
another object of the present invention is to provide a process for preparing the above sulfur-containing bergenin derivative having antioxidant activity.
The technical scheme of the invention is that bergenin and thiodipropionic acid are used as raw materials to react in an organic solvent, nitrogen is adopted for protection in the reaction process, and a crude product obtained by the reaction is absorbed and purified by macroporous resin, so that the sulfur-containing bergenin derivative can be obtained.
The synthetic route of the compound provided by the invention is as follows:
in order to realize the synthetic route, the synthetic steps of the invention are as follows:
(1) dissolving a proper amount of bergenin and thiodipropionic acid by using an organic solvent, placing the solution in a reactor, introducing nitrogen for protection, adding a certain amount of dehydrating agent into the reaction system under magnetic stirring, heating the solution to 50-60 ℃, and reacting the solution for 15-17 hours.
(2) The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative.
(3) And (3) adsorbing and purifying the lower layer grease obtained in the step (2) by adopting macroporous resin, eluting and enriching by adopting an organic solvent as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating under reduced pressure to obtain the refined product of the sulfur-containing bergenin derivative.
The organic solvent in the step (1) is preferably acetonitrile or tetrahydrofuran, and more preferably acetonitrile.
The molar ratio of bergenin to thiodipropionic acid in the above step (1) is preferably 2.1: 1.
The dehydrating agent in the step (1) is preferably DCC, concentrated sulfuric acid, EDC, or the like, and more preferably EDC.
The reaction temperature in the above step (1) is preferably 60 ℃.
The reaction time in the above step (1) is preferably 16 hours.
The macroporous resin in the step (3) is preferably polar macroporous resin, and is preferably AB-8 type macroporous adsorption resin.
The eluent in the above step (3) is preferably methanol.
The invention has the beneficial effects that:
the reaction conditions are mild, the reaction steps are few, the pollution in the reaction process is small, and the method is suitable for industrial production. The antioxidant experiment result shows that the compound has excellent antioxidant activity and can be used as a novel antioxidant to be deeply developed and applied in the fields of food, medicine and health care products.
Drawings
FIG. 1 shows the result of DPPH radical scavenging experiment.
Detailed Description
The invention will be further illustrated with reference to specific examples. These examples are for illustrative purposes only and do not limit the scope and spirit of the present invention.
Example 1
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 233mg (0.71mmol) of bergenin and 60mg (0.34mmol) of thiodipropionic acid are dissolved in 40mL of acetonitrile according to a feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And further adsorbing and purifying the crude product by using macroporous resin AB-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain a refined bergenin thiodipropionate derivative product 144mg with the total yield of 52.9%.
1H-NMR(400MHz,DMSO-d6)δ(ppm):9.37(2H,s),9.24(2H,s),6.89(2H,s),5.47(2H,d),5.01(2H,m),4.41-4.23(6H,m),4.10-3.95(6H,m),3.57(6H,s),3.34(2H,m),2.48(4H,t),2.35(4H,t)；13C-NMR(75MHz,DMSO-d6)δ(ppm):165.1,160.5,143.2,140.4,139.5,119.8,111.7,103.2,75.2,73.5,69.9,68.7,65.9,57.1,53.8,27.5,22.6；MS(ESI)for(M+H)+:799.7.
Example 2
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 338mg (1.03mmol) of bergenin and 87mg (0.49mmol) of thiodipropionic acid are dissolved in 40mL of acetonitrile according to the charge ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of DCC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And further adsorbing and purifying the crude product by using macroporous resin AB-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain a refined bergenin thiodipropionate derivative product of 137.8mg, wherein the total yield is 35.2%.
Example 3
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
Dissolving bergenin 233mg (0.71mmol) and thiodipropionic acid 60mg (0.34mmol) in acetonitrile 40mL at a feed ratio in a 100mL three-neck flask, introducing nitrogen for protection, adding a certain amount of dehydrating agent concentrated H under magnetic stirring2SO4The reaction system is heated to 60 ℃ and reacted for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And (3) further adsorbing and purifying the crude product by using macroporous resin ADS-2, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain 107.3mg of the refined bergenin thiodipropionate derivative product with the total yield of 39.5%.
Example 4
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 338mg (1.03mmol) of bergenin and 87mg (0.49mmol) of thiodipropionic acid are dissolved in 40mL of tetrahydrofuran according to the feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And further adsorbing and purifying the crude product by using macroporous resin AB-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain the refined bergenin thiodipropionate derivative product 152.4mg with the total yield of 38.9%.
Example 5
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 233mg (0.71mmol) of bergenin and 60mg (0.34mmol) of thiodipropionic acid are dissolved in 40mL of tetrahydrofuran according to the charge ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of DCC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And (3) further adsorbing and purifying the crude product by using macroporous resin S-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain refined bergenin thiodipropionate derivative 51.9mg with the total yield of 19.1%.
Example 6
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 338mg (1.03mmol) of bergenin and 87mg (0.49mmol) of thiodipropionic acid are dissolved in 40mL of tetrahydrofuran according to the feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent concentrated H2SO4 is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And further adsorbing and purifying the crude product by using macroporous resin AB-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain refined bergenin thiodipropionate derivative product 114.1mg with the total yield of 29.1%.
Example 7
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 233mg (0.71mmol) of bergenin and 60mg (0.34mmol) of thiodipropionic acid are dissolved in 40mL of acetonitrile according to a feeding ratio (bergenin: thiodipropionic acid (2.1:1)), and under the protection of nitrogen gas, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And further adsorbing and purifying the crude product by using macroporous resin AB-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain 104.1mg of the refined bergenin thiodipropionate derivative with the total yield of 38.3%.
Example 8
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 338mg (1.03mmol) of bergenin and 87mg (0.49mmol) of thiodipropionic acid are dissolved in 40mL of acetonitrile according to the feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And (3) further adsorbing and purifying the crude product by using macroporous resin ADS-2, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain the refined bergenin thiodipropionate derivative product of 103.1mg, wherein the total yield is 26.3%.
Example 9
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 233mg (0.71mmol) of bergenin and 60mg (0.34mmol) of thiodipropionic acid are dissolved in 40mL of tetrahydrofuran according to the feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And (3) further adsorbing and purifying the crude product by using macroporous resin S-8, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain 116.3mg of the refined bergenin thiodipropionate derivative with the total yield of 42.8%.
Example 10
Preparation of bis ((3,4,8,10-tetrahydroxy-9-methoxy-6-oxo-2,3,4,4a,6,10b-hexahydropyrano [3,2-c ] isochromen-2-yl) methyl)3,3' -thiodipropionate
In a 100mL three-neck flask, 338mg (1.03mmol) of bergenin and 87mg (0.49mmol) of thiodipropionic acid are dissolved in 40mL of tetrahydrofuran according to the feeding ratio (bergenin: thiodipropionic acid (2.1:1)), nitrogen is introduced for protection, a certain amount of dehydrating agent EDC is added into the reaction system under magnetic stirring, and the reaction system is heated to 60 ℃ for about 16 hours. The thin layer chromatography was followed until the reaction was complete, heating was stopped, and the protection device was removed. And (3) concentrating the reaction mixed system under reduced pressure, standing the concentrated solution for layering, and taking the lower oil phase to obtain a crude product of the bergenin thiodipropionate derivative. And (3) further adsorbing and purifying the crude product by using macroporous resin ADS-2, repeatedly eluting and enriching the eluent by using methanol as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating the oil layer under reduced pressure to obtain the refined product 172mg of the bergenin thiodipropionate derivative, wherein the total yield is 43.9%.
Example 11
DPPH free radical scavenging experiment
The experimental principle is as follows:
in DPPH molecule, multiple electron-withdrawing-NO molecules exist2And a large pi bond of a benzene ring, so that a nitrogen radical can exist stably. The ethanol solution is purple, and has a maximum absorption peak at 517 nm. After the antioxidant is added, DPPH captures an electron to be paired with a free electron, the purple fades and becomes a yellow substance, the absorption at 517nm disappears, and the fading degree is accepted by the DPPHThe number of electrons in (a) is in a quantitative relationship. According to the principle, a spectrophotometer is used for detecting the change of the light absorption value after the DPPH free radical reacts with the sample liquid, so that the oxidation resistance of the sample for providing hydrogen atoms and removing free radicals can be detected.
The experimental method comprises the following steps:
(a) preparation of a DPPH test solution: accurately weighing a certain amount of 1, 1-diphenyl-2-picrylhydrazine free radical, and dissolving with methanol to obtain 2 x 10-4And (3) storing the DPPH solution in mol/L in a dark place.
(b) Preparing a solution to be detected: vc (positive control), bergenin thiodipropionate derivative (sample), bergenin (control), thiodipropionic acid (control), and a mixed solution of bergenin and thiodipropionic acid (control), wherein acetonitrile is used for carrying out gradient dilution on a sample solution, and 4 groups of controls are respectively dissolved in a test tube by adopting a certain amount of methanol to prepare a concentration gradient which is the same as that of the sample. Corresponding 4 sets of control solutions were obtained (gradient setup see table 1).
TABLE 1 dilution gradient of test solution
(c) The operation method comprises the following steps:
and (3) measuring the absorbance of the sample solution: 2mL of sample solution (Table 1B) was added at 2X 10-42mL of a DPPH solution in mol/L, uniformly mixing, reacting for 30min in the dark at room temperature, adjusting to zero with methanol, measuring the absorbance Ai at 517nm, and simultaneously measuring the absorbance Aj after 2mL of methanol is mixed with 2mL of a sample solution and the absorbance Ao after 2mL of the DPPH solution is mixed with 2mL of acetonitrile (the experimental results are shown in Table 2).
And (3) measuring the absorbance of the reference substance: 2mL of the control solution (Table 1C, D, E) from step (b) was added at 2X 10 concentration-42mL of DPPH solution in mol/L, uniformly mixing, reacting for 30min in a dark place at room temperature, adjusting to zero by methanol, measuring the absorbance Ai at 517nm, and simultaneously measuring 2mL of methanol and 2mL of methanolThe absorbance Aj of the control solution after mixing and the absorbance Ao of the 2mL DPPH solution after mixing with 2mL methanol (see Table 2 for experimental results).
TABLE 2 Absorbance test results of solutions to be tested
(d) Calculation of clearance rate: the clearance (%) [1- (Ai-Aj)/Ao ]. 100%
TABLE 3DPPH Rate of removal test results
As can be seen from the results of the experiments in table 1-table 3 and fig. 1, the compound bergenin thiodipropionate derivative (B) exhibited a significant effect of removing DPPH in a concentration-dependent manner. The clearance rate of the compound to DPPH is from 28.01% (0.04mg/mL) to 96.22% (33.12mg/mL), compared with single bergenin (C), thiodipropionic acid (D) and a mixed solution (2:1) (E) of bergenin and thiodipropionic acid, the bergenin thiodipropionate derivative (B) has obviously better capacity to DPPH under the same concentration, and the clearance effect of B to DPPH is close to the clearance capacity of Vc when the concentration reaches above 24.84mg/mL, reaching 96.22.
Claims (10)
1. A sulfur-containing bergenin derivative with antioxidant activity is characterized in that the structural formula is shown as formula I:
2. a method for synthesizing sulfur-containing bergenin derivative with antioxidant activity is characterized in that bergenin and thiodipropionic acid are used as raw materials to react in an organic solvent under the action of a dehydrating agent, nitrogen is adopted for protection in the reaction process, and after the reaction is finished, a crude product is adsorbed and purified by macroporous resin to obtain the sulfur-containing bergenin derivative, wherein the synthetic route is as follows:
3. the method for synthesizing sulfur-containing bergenin derivative with antioxidant activity as claimed in claim 2, wherein the synthesizing steps are as follows:
(1) dissolving a proper amount of bergenin and thiodipropionic acid by using an organic solvent, placing the solution in a reactor, introducing nitrogen for protection, adding a certain amount of dehydrating agent into the reaction system under magnetic stirring, heating the solution to 50-60 ℃, and reacting the solution for 15-17 hours;
(2) tracking the reaction to be complete by a thin layer chromatography method, stopping heating, removing a protection device, decompressing and concentrating a reaction mixed system, standing and layering a concentrated solution, and taking a lower layer oil phase to obtain a crude product of the bergenin thiodipropionate derivative;
(3) and (3) adsorbing and purifying the lower layer grease obtained in the step (2) by adopting macroporous resin, eluting and enriching by adopting an organic solvent as an eluent, adding anhydrous sodium sulfate into the eluent for drying, and concentrating under reduced pressure to obtain the refined product of the sulfur-containing bergenin derivative.
4. The method for synthesizing sulfur-containing bergenin derivative with antioxidant activity as claimed in claim 3, wherein the organic solvent in step (1) is acetonitrile or tetrahydrofuran.
5. The method for synthesizing sulfur-containing bergenin derivative with antioxidant activity as claimed in claim 3, wherein the molar ratio of bergenin to thiodipropionic acid in step (1) is 2: 1-2.2: 1.
6. The method for synthesizing sulfur-containing bergenin derivative with antioxidant activity according to claim 3, wherein the dehydrating agent in step (1) is DCC, concentrated sulfuric acid or EDC.
7. The method for synthesizing sulfur-containing bergenin derivative with antioxidant activity as claimed in claim 3, wherein the reaction temperature in step (1) is 60 ℃ and the reaction time is 16 hours.
8. The method for synthesizing sulfur-containing bergenin derivative with antioxidant activity as claimed in claim 3, wherein the macroporous resin in step (3) is a polar macroporous resin type AB-8, S-8 or ADS-2.
9. The method as claimed in claim 3, wherein the eluent used in step (3) is methanol.
10. The use of the sulfur-containing bergenin derivative of claim 1 as an antioxidant additive in the preparation of food, pharmaceuticals, and health products.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810649370.6A CN108997379B (en) | 2018-06-22 | 2018-06-22 | Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810649370.6A CN108997379B (en) | 2018-06-22 | 2018-06-22 | Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108997379A CN108997379A (en) | 2018-12-14 |
| CN108997379B true CN108997379B (en) | 2021-02-12 |
Family
ID=64601071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810649370.6A Active CN108997379B (en) | 2018-06-22 | 2018-06-22 | Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108997379B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10487094B1 (en) * | 2018-09-03 | 2019-11-26 | Shaanxi University Of Science And Technology | Bergenin thiodipropionic acid ester with antioxidant activity and a method of improving the antioxidant property of ganoderma lucidum spore oil using the same |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997010233A1 (en) * | 1995-09-11 | 1997-03-20 | Enzymed, Inc. | Biocatalytic methods for synthesizing and identifying biologically active compounds |
| CN1733766A (en) * | 2005-07-21 | 2006-02-15 | 四川滇虹医药开发有限公司 | Cough and phlegm removing purple bergenia element analog and its pharmaceutical composition |
| JP2008169174A (en) * | 2007-01-15 | 2008-07-24 | Yoshihiro Futamura | Bergenin derivative having inflammatory cytokine production-inhibiting action, food preparation, cosmetic, antiinflammatory agent comprising the same |
| CN101812068A (en) * | 2010-03-22 | 2010-08-25 | 云南大学 | Bergenin derivative and preparation method thereof |
| CN106432259A (en) * | 2016-07-28 | 2017-02-22 | 广州科技职业技术学院 | Bergenin derivative and synthetic method and application thereof |
| CN106632379A (en) * | 2016-12-31 | 2017-05-10 | 陕西科技大学 | Bergenin azacinnamate compound with anti-tumor activity and synthetic method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101384634B1 (en) * | 2012-01-16 | 2014-04-11 | 이화여자대학교 산학협력단 | A pharmaceutical composition for treating narcotics addiction comprising bergenin or bergenin derivatives |
-
2018
- 2018-06-22 CN CN201810649370.6A patent/CN108997379B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997010233A1 (en) * | 1995-09-11 | 1997-03-20 | Enzymed, Inc. | Biocatalytic methods for synthesizing and identifying biologically active compounds |
| CN1733766A (en) * | 2005-07-21 | 2006-02-15 | 四川滇虹医药开发有限公司 | Cough and phlegm removing purple bergenia element analog and its pharmaceutical composition |
| JP2008169174A (en) * | 2007-01-15 | 2008-07-24 | Yoshihiro Futamura | Bergenin derivative having inflammatory cytokine production-inhibiting action, food preparation, cosmetic, antiinflammatory agent comprising the same |
| CN101812068A (en) * | 2010-03-22 | 2010-08-25 | 云南大学 | Bergenin derivative and preparation method thereof |
| CN106432259A (en) * | 2016-07-28 | 2017-02-22 | 广州科技职业技术学院 | Bergenin derivative and synthetic method and application thereof |
| CN106632379A (en) * | 2016-12-31 | 2017-05-10 | 陕西科技大学 | Bergenin azacinnamate compound with anti-tumor activity and synthetic method thereof |
Non-Patent Citations (3)
| Title |
|---|
| "A carbon–carbon-coupled dimeric bergenin derivative biotransformed by Pleurotus ostreatus";Dong Wang et al.;《Bioorganic & Medicinal Chemistry Letters》;20050701;第15卷;第4073-4075页 * |
| "Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids";Chengyuan Liang et al.;《European Journal of Medicinal Chemistry》;20170403;第133卷;第319-328页 * |
| "岩白菜素及其衍生物抗炎活性的相关研究进展";邓丽华 等;《药学研究》;20161231;第35卷(第7期);第408-411页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108997379A (en) | 2018-12-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Domínguez-Álvarez et al. | Synthesis and antiproliferative activity of novel selenoester derivatives | |
| Coxon et al. | The Structure of 2, 3, 4, 6-Tetra-O-acetyl-β-D-galactopyranosyl Cyanide and Some Derivatives Therefrom. Synthesis of 1-Deoxy-D-galacto-heptulose | |
| CN108997379B (en) | Sulfur-containing bergenin derivative with antioxidant activity and synthesis method thereof | |
| CN115304609B (en) | Pyrazolopyrimidine ester compound crystal form and preparation method thereof | |
| CN110078695B (en) | Quercetin derivative and preparation method thereof | |
| CN112094191B (en) | Hydroxytyrosol dihydrocaffeic acid ester with antioxidant activity and synthetic method thereof | |
| CN111103375B (en) | Application of chlorogenic acid derivative in medicine quality control | |
| JP6741315B2 (en) | Esculin lipoic acid ester having antioxidant activity and method for producing the same | |
| CN116459288A (en) | New use of Cinnamomum camphora leaf sesquiterpene extract | |
| CN109970608B (en) | Hydroxytyrosol thiodipropionate with antioxidant activity and synthesis method thereof | |
| JP6934264B2 (en) | Hydroxytyrosol p-phenylenedicarboxylate having antioxidant activity and its preparation method | |
| US10487094B1 (en) | Bergenin thiodipropionic acid ester with antioxidant activity and a method of improving the antioxidant property of ganoderma lucidum spore oil using the same | |
| CN103159702B (en) | Synthesis of 1-substituent-5-isopropyl-3, 8-dimethyl azulenyl sulfonyl piperazine and anti-gastric ulcer activity research | |
| CN113511967B (en) | Method for extracting quinic acid from ginkgo leaf extract chromatographic wastewater | |
| CN114426538A (en) | Berberine canagliflozin derivative and preparation method and application thereof | |
| CN114262337A (en) | Procaine penicillin, preparation method thereof, impurities and impurity control method | |
| CN111592484A (en) | Preparation method of 5-aminolevulinic acid hydrochloride intermediate | |
| CN111454310A (en) | Preparation method of rutin metal complex | |
| CN111675740A (en) | Potholin glucoside, application of pinosylin glucoside and preparation method of pinosylin glucoside | |
| JP6940201B1 (en) | Hydroxytyrosol ursodeoxycholic acid ester having antioxidant activity and its preparation method | |
| CN117164742B (en) | Carboxymethyl inulin derivative containing bipyridyl Schiff base, and preparation method and application thereof | |
| CN108586564A (en) | A kind of C5 replaces diosgenin derivative and its preparation and application | |
| WO2022241749A1 (en) | Method for chemical synthesis of prodelphinidin b9 gallate | |
| JPH0350758B2 (en) | ||
| CN109180759B (en) | Method for separating and purifying formononetin from liquorice waste residue |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221116 Address after: 710075 room a-117-11, I chuangtu Zhongchuang Park, No. 14, Gaoxin Second Road, high tech Zone, Xi'an, Shaanxi Province Patentee after: Xi'an kangyuansheng Biomedical Technology Co.,Ltd. Address before: 710021 Shaanxi province Xi'an Weiyang university campus of Shaanxi University of Science and Technology Patentee before: SHAANXI University OF SCIENCE & TECHNOLOGY |