CN110590800A - 7-p-benzoic acid azobergenin and preparation method and application thereof - Google Patents
7-p-benzoic acid azobergenin and preparation method and application thereof Download PDFInfo
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- 239000005711 Benzoic acid Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- XULPLJSODQQHPH-UHFFFAOYSA-N Bergenin Natural products OCC1OC2C(OC(=O)c3cc(O)c(CO)c(O)c23)C(O)C1O XULPLJSODQQHPH-UHFFFAOYSA-N 0.000 claims abstract description 52
- -1 azo bergenin Chemical compound 0.000 claims abstract description 32
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims abstract description 30
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 30
- YWJXCIXBAKGUKZ-HJJNZUOJSA-N Bergenin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]2C3=C(O)C(OC)=C(O)C=C3C(=O)O[C@@H]21 YWJXCIXBAKGUKZ-HJJNZUOJSA-N 0.000 claims abstract description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- AHSWGWIUVXBWEE-UHFFFAOYSA-N (diazonioamino)benzene Chemical class N#[N+]NC1=CC=CC=C1 AHSWGWIUVXBWEE-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960004050 aminobenzoic acid Drugs 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000007864 aqueous solution Substances 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000006193 diazotization reaction Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 9
- 238000004809 thin layer chromatography Methods 0.000 claims description 8
- 230000000954 anitussive effect Effects 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 229940124584 antitussives Drugs 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- 239000012954 diazonium Substances 0.000 claims description 3
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000005292 vacuum distillation Methods 0.000 claims description 3
- 150000001989 diazonium salts Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 claims 9
- 230000000694 effects Effects 0.000 abstract description 21
- 206010011224 Cough Diseases 0.000 abstract description 15
- 231100000419 toxicity Toxicity 0.000 abstract description 7
- 230000001988 toxicity Effects 0.000 abstract description 7
- 238000012360 testing method Methods 0.000 abstract description 5
- 206010062717 Increased upper airway secretion Diseases 0.000 description 7
- 208000026435 phlegm Diseases 0.000 description 7
- 230000003419 expectorant effect Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000471262 Ardisia japonica Species 0.000 description 1
- 241001092376 Astilbe Species 0.000 description 1
- 241000202903 Bergenia purpurascens Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses 7-p-benzoic acid azo bergenin and a preparation method and application thereof, and the preparation method of the 7-p-benzoic acid azo bergenin disclosed in claim 1 comprises the following steps: (1) firstly, taking p-aminobenzoic acid and sodium nitrite as raw materials, adding a sodium nitrite aqueous solution under the stirring condition of an ice salt bath when the p-aminobenzoic acid is dissolved in dilute hydrochloric acid, and carrying out diazotization reaction at the temperature of 0-5 ℃ to obtain aniline diazonium salt; (2) the aniline diazonium salt is coupled with bergenin compound to react, stirred under alkaline condition, and modulated to weak acidity after the bergenin is dissolved in sodium hydroxide and added with the aniline diazonium salt to react until the reaction is finished, thus preparing the 7-p-benzoic acid azo bergenin; the 7-p-benzoic acid azo bergenin obtained by the invention has better effect on relieving cough through cough activity test, and the compound has better water solubility, better activity, lower toxicity and increased bioavailability.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to 7-p-benzoic acid azo bergenin and a preparation method and application thereof.
Background
Bergenin (Bergenin) is an effective component extracted from 88 plants of 37 genus of 20 families, such as Bergenia purpurascens, astilbes chinensis and Japanese ardisia japonica, has a molecular formula of C14H16O9, belongs to a dihydroisocoumarin compound, is white loose needle crystal or crystalline powder, is dissolved in methanol, and is slightly soluble in water, acetone or ethanol. The bergenin has certain effect of relieving cough and eliminating phlegm, and the N atom is introduced into the bergenin mother nucleus by a chemical method to synthesize azo compounds so as to improve the activity of the bergenin compounds for relieving cough and eliminating phlegm.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide 7-p-benzoic acid azo bergenin with cough relieving and phlegm eliminating activities, a preparation method and application thereof.
Another object of the present invention is to provide 7-p-benzoic acid azo bergenin obtained by the above preparation method.
The invention also aims to provide application of the 7-p-benzoic acid azobergenin.
The invention provides the following technical scheme: the structural formula of the 7-p-benzoic acid azo bergenin is shown in a formula II:
the preparation method of 7-p-benzoic acid azo bergenin comprises the following steps: (1) firstly, taking p-aminobenzoic acid and sodium nitrite as raw materials, adding a sodium nitrite aqueous solution under the stirring condition of an ice salt bath when the p-aminobenzoic acid is dissolved in dilute hydrochloric acid, and carrying out diazotization reaction at the temperature of 0-5 ℃ to obtain aniline diazonium salt;
(2) the aniline diazonium salt is coupled with bergenin compound to react, stirred under alkaline condition, and modulated to weak acidity after the bergenin is dissolved in sodium hydroxide and added with the aniline diazonium salt to react until the reaction is finished, thus preparing the 7-p-benzoic acid azo bergenin;
the p-aminobenzoic acid: the mass ratio of the sodium nitrite aqueous solution is 2.32: 1.04, the ratio of p-aminobenzoic acid: the mass-volume ratio of the dilute hydrochloric acid is 25.5 mg: 3ml (2 mol/L).
Further, in step (1), the structural formula of the aniline diazonium salt is shown as formula I:
further, in the step (1), the benzoic acid is 2.32g, the diluted hydrochloric acid is 240ml (2mol/L), and the aqueous solution of sodium nitrite is 240ml (1.04 g); the ice salt bath temperature was 4 ℃.
Further, in the step (1), a step of purifying the diazonium salt of p-aniline is also included.
Further, in the step (1), dilute hydrochloric acid is used to adjust the pH to weak acidity.
Further, in the step (2), the bergenin is 4g, and the sodium hydroxide is 15ml (2 mol/L).
Further, in the step (2), the reaction temperature is 10 ℃, the reaction time is 20 minutes and 60 minutes, the pH is adjusted to weak acidity by using dilute hydrochloric acid after 20 minutes of reaction, and the end point of the coupling reaction is checked by using Thin Layer Chromatography (TLC) and iodine color development after 1 hour of reaction.
Further, in the step (2), after vacuum distillation and concentration, the mixture is separated by 300-400 mesh silica gel column chromatography, and is eluted by a mixed solution of ethyl acetate, ethanol and water, wherein the weight ratio of ethyl acetate: ethanol: the volume ratio of water is 7:3:1, and the compound 7-p-benzoic acid azo bergenin is obtained.
The invention relates to application of 7-p-benzoic acid azo bergenin in preparing antitussive medicines.
Has the advantages that: the 7-p-benzoic acid azo bergenin obtained by the invention has better effect on relieving cough through cough activity test, and the compound has better water solubility, better activity, lower toxicity and increased bioavailability. The results show that the cough frequency is obviously reduced within 3 minutes, and the effect is better than the effect of bergenin. Acute toxicity test shows that the toxicity is small, and the cough-relieving phlegm-eliminating medicament with small toxicity and strong activity is expected to be prepared.
Detailed Description
The invention is further illustrated by the following examples. It should be understood that these examples are illustrative and exemplary of the present invention, and are not intended to limit the scope of the present invention in any way.
Example 1
The structural formula of the 7-p-benzoic acid azo bergenin is shown in a formula II:
the preparation method of 7-p-benzoic acid azo bergenin comprises the following steps: (1) firstly, taking p-aminobenzoic acid and sodium nitrite as raw materials, adding a sodium nitrite aqueous solution under the stirring condition of an ice salt bath when the p-aminobenzoic acid is dissolved in dilute hydrochloric acid, and carrying out diazotization reaction at the temperature of 0-5 ℃ to obtain aniline diazonium salt;
the structural formula of the aniline diazonium salt is shown as a formula I:
the weight ratio of the benzoic acid to the dilute hydrochloric acid is 2.32g, the weight ratio of the dilute hydrochloric acid to the dilute hydrochloric acid is 240ml (2mol/L), and the weight ratio of the sodium nitrite aqueous solution to the dilute hydrochloric acid is 240ml (1.04 g); the ice salt bath temperature was 4 ℃. Also comprises a purification step of the para-aniline diazonium salt. Dilute hydrochloric acid is used to adjust the pH to weak acidity.
(2) The aniline diazonium salt is coupled with bergenin compound to react, stirred under alkaline condition, and modulated to weak acidity after the bergenin is dissolved in sodium hydroxide and added with the aniline diazonium salt to react until the reaction is finished, thus preparing the 7-p-benzoic acid azo bergenin;
the p-aminobenzoic acid: the mass ratio of the sodium nitrite aqueous solution is 2.32: 1.04, the ratio of p-aminobenzoic acid: the mass-volume ratio of the dilute hydrochloric acid is 25.5 mg: 3ml (2 mol/L).
The bergenin is 4g, and the sodium hydroxide is 15ml (2 mol/L). The reaction temperature is 10 ℃, the reaction time is 20 minutes and 60 minutes respectively, the pH is adjusted to weak acidity by dilute hydrochloric acid after 20 minutes of reaction, and the end point of the coupling reaction is checked by Thin Layer Chromatography (TLC) and iodine color development after 1 hour of reaction. Carrying out vacuum distillation and concentration, then carrying out 300-400-mesh silica gel column chromatography, and eluting with a mixed solution of ethyl acetate, ethanol and water, wherein the weight ratio of ethyl acetate: ethanol: the volume ratio of water is 7:3:1, and the compound 7-p-benzoic acid azo bergenin is obtained.
The invention relates to application of 7-p-benzoic acid azo bergenin in preparing antitussive medicines.
Example 2
Example 2 differs from example 1 in that: the invention provides a preparation method of 7-p-benzoic acid azo bergenin, which comprises the following steps: 25.4mg of p-aminobenzoic acid is ultrasonically dissolved in 3ml of dilute hydrochloric acid (2mol/L) and placed in a 50ml round-bottom flask ice salt bath, the temperature is kept between 0 and 5 ℃, the solution is slowly dripped into 3ml of aqueous solution containing 13mg of sodium nitrite under stirring, and the reaction progress is detected by a starch potassium iodide test paper. Taking another 50ml round-bottom flask, dissolving 50mg of bergenin in 4ml of sodium hydroxide (2mol/L) aqueous solution, dropwise adding the prepared diazo p-aminobenzoate solution under stirring, checking the coupling reaction end point by Thin Layer Chromatography (TLC) and iodine color development, separating by 300-mesh 400-mesh silica gel column chromatography after reduced pressure distillation and concentration, eluting by a mixed solution of ethyl acetate, ethanol and water, wherein the weight ratio of ethyl acetate: ethanol: the volume ratio of water is 7:3:1, and 7-p-benzoic acid azo bergenin is obtained.
Reaction formula of 7-p-benzoic acid azo bergenin
Compound KY406, a reddish brown powdered solid, readily soluble in water, 60% yield.
The identification result data of the prepared 7-p-benzoic acid azo bergenin are as follows:1H-NMR(500MHz，D2O)δ：7.86(2H，m，H-3′、5′)；7.62(2H，m，H-2′、6′)；4.71(1H，d，H-10b)；4.36(1H，m，H-4a)；4.16(1H，m，H-4)；3.70(1H，m，H-2)；3.88(1H，m，H-11)；3.45(1H，m，H-3)；13C-NMR(125MHz，D2O)δ：174.18(C-4′-COOH)，172.73(C-6)，157.51(C-1′)，156.70(C-10)，148.27(C-9)，143.33(C-8)，134.57(C-7)，133.37(C-4′)，130.53(C-3′)，119.57(C-2′)，129.12(C-10a)，113.58(C-6a)，80.24(C-4a)，77.98(C-2)，77.59(C-4)，71.40(C-3)，69.62(C-10b)，60.96(C-11)，60.49(9-OCH3)；ESI-MS(m/z):477.11[M+H]+.
test example 1
The 7-p-benzoic acid azo bergenin obtained by the invention has better effect on relieving cough through cough activity test, and the compound has better water solubility, better activity, lower toxicity and increased bioavailability. The results show that the cough frequency is obviously reduced within 3 minutes, and the effect is better than the effect of bergenin. Acute toxicity test shows that the toxicity is small, and the cough-relieving phlegm-eliminating medicament with small toxicity and strong activity is expected to be prepared.
The statistical results of cough-relieving and phlegm-eliminating experiments of bergenin and derivatives thereof show that the comparison of cough-relieving effects of bergenin and derivatives thereof (X ± S n ═ 8) is shown in table 1:
TABLE 1
Note: comparison with the model set: p < 0.05P < 0.01P <0.001
The antitussive effect of each derivative compared to bergenin (X ± S n ═ 8) is shown in table 2:
TABLE 2
Note: comparison with bergenin group: p < 0.05P <0.01
KY406 is arranged below the 7-p-benzoic acid azobergenin.
Comparison of antitussive Activity: KY406> KY607> KY442> bergenin > KY605, wherein KY406 has the strongest antitussive activity.
The statistical results of the phlegm-eliminating experiments of bergenin and derivatives thereof are shown in table 3:
TABLE 3
The comparison of expectorant effects of bergenin and its derivatives (X ± S n ═ 8) is shown in table 4,
TABLE 4
Note: comparison with saline group: the comparison of the expectorant effect of each derivative P < 0.05P < 0.01P <0.001 with bergenin (X ± S n ═ 8) is shown in table 5,
TABLE 5
Note: comparison with bergenin group: p < 0.05P < 0.01P <0.001
As shown in table 5, the expectorant activity was compared: KY406> KY605> KY607> KY442> bergenin, wherein KY406 has the strongest expectorant activity.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the foregoing description only for the purpose of illustrating the principles of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the invention as defined by the appended claims, specification, and equivalents thereof.
Claims (10)
1. 7-p-benzoic acid azo bergenin, which is characterized in that: the structural formula of the 7-p-benzoic acid azobergenin is shown as a formula II:
2. a process for the preparation of 7-azobergenin terephthalate according to claim 1, characterized by comprising the steps of: (1) firstly, taking p-aminobenzoic acid and sodium nitrite as raw materials, adding a sodium nitrite aqueous solution under the stirring condition of an ice salt bath when the p-aminobenzoic acid is dissolved in dilute hydrochloric acid, and carrying out diazotization reaction at the temperature of 0-5 ℃ to obtain aniline diazonium salt;
(2) the aniline diazonium salt is coupled with bergenin compound to react, stirred under alkaline condition, and modulated to weak acidity after the bergenin is dissolved in sodium hydroxide and added with the aniline diazonium salt to react until the reaction is finished, thus preparing the 7-p-benzoic acid azo bergenin;
the p-aminobenzoic acid: the mass ratio of the sodium nitrite aqueous solution is 2.32: 1.04, the ratio of p-aminobenzoic acid: the mass-volume ratio of the dilute hydrochloric acid is 25.5 mg: 3ml (2 mol/L).
3. The method for preparing 7-azobergenine terephthalate according to claim 1, wherein: in the step (1), the structural formula of the aniline diazonium salt is shown as the formula I:
4. the method for preparing 7-azobergenine terephthalate according to claim 1, wherein: in the step (1), the benzoic acid is 2.32g, the diluted hydrochloric acid is 240ml (2mol/L), and the sodium nitrite aqueous solution is 240ml (1.04 g); the ice salt bath temperature was 4 ℃.
5. The process for the preparation of 7-azobergenine terephthalate according to claim 4, characterized in that: in the step (1), a purification step of the diazonium salt of p-aniline is also included.
6. The process for the preparation of 7-azobergenine terephthalate according to claim 5, characterized in that: in step (1), dilute hydrochloric acid is used to adjust the pH to weak acidity.
7. The method for preparing 7-azobergenine terephthalate according to claim 1, wherein: in the step (2), the bergenin is 4g, and the sodium hydroxide is 15ml (2 mol/L).
8. The process for the preparation of 7-azobergenine terephthalate according to claim 7, wherein: in the step (2), the reaction temperature is 10 ℃, the reaction time is 20 minutes and 60 minutes respectively, the pH is adjusted to weak acidity by using dilute hydrochloric acid after the reaction is carried out for 20 minutes, and the end point of the coupling reaction is checked by using Thin Layer Chromatography (TLC) and iodine color development after the reaction is carried out for 1 hour.
9. The method for preparing 7-azobergenine terephthalate according to claim 1, wherein: in the step (2), after vacuum distillation and concentration, the mixture is separated by a 300-400-mesh silica gel column chromatography, and is eluted by a mixed solution of ethyl acetate, ethanol and water, wherein the weight ratio of ethyl acetate: ethanol: the volume ratio of water is 7:3:1, and the compound 7-p-benzoic acid azo bergenin is obtained.
10. Use of 7-azobergenin terephthalate according to any one of claims 1 to 9 for the preparation of an antitussive medicament.
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| CN105037382A (en) * | 2015-07-07 | 2015-11-11 | 中国药科大学 | Bergenin derivatives, and preparation method and application thereof |
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|---|---|---|---|---|
| CN101812068A (en) * | 2010-03-22 | 2010-08-25 | 云南大学 | Bergenin derivative and preparation method thereof |
| WO2014188440A1 (en) * | 2013-05-24 | 2014-11-27 | Council Of Scientific & Industrial Research | Tetrahydro-2h-pyrano[3,2-c]isochromene-6-ones and analogs for the treatment of inflammatory disorders |
| CN104725393A (en) * | 2015-02-02 | 2015-06-24 | 新乡医学院 | Bergenin derivative as well as preparation method and application thereof |
| CN105037382A (en) * | 2015-07-07 | 2015-11-11 | 中国药科大学 | Bergenin derivatives, and preparation method and application 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 |
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