CN113968894A - Method for preparing cycloastragenol by degrading astragaloside - Google Patents
Method for preparing cycloastragenol by degrading astragaloside Download PDFInfo
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- astragaloside
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- WENNXORDXYGDTP-UOUCMYEWSA-N cycloastragenol Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O)C4(C)C)[C@H]4[C@@H](O)C[C@H]3[C@]2(C)C[C@@H]1O WENNXORDXYGDTP-UOUCMYEWSA-N 0.000 title claims abstract description 48
- WENNXORDXYGDTP-UHFFFAOYSA-N cyclosiversigenin Natural products O1C(C(C)(O)C)CCC1(C)C1C2(C)CCC34CC4(CCC(O)C4(C)C)C4C(O)CC3C2(C)CC1O WENNXORDXYGDTP-UHFFFAOYSA-N 0.000 title claims abstract description 48
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 title claims abstract description 42
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 31
- 230000000593 degrading effect Effects 0.000 title claims abstract description 15
- 238000006731 degradation reaction Methods 0.000 claims abstract description 34
- 230000015556 catabolic process Effects 0.000 claims abstract description 30
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 239000011973 solid acid Substances 0.000 claims abstract description 14
- 150000002191 fatty alcohols Chemical class 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 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 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000005526 G1 to G0 transition Effects 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 229910000342 sodium bisulfate Inorganic materials 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical group [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical group [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims description 3
- 229910000343 potassium bisulfate Inorganic materials 0.000 claims description 3
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- KNESISUQBYQIIU-UHFFFAOYSA-N 6-Angeloyl-1,6-Dihydroxyfuranoeremophilan-9-one Natural products O1C(C(C)(O)C)CCC1(C)C1C2(C)CC=C3C4(C)CCC(O)C(C)(C)C4C(O)CC3C2(C)CC1O KNESISUQBYQIIU-UHFFFAOYSA-N 0.000 abstract description 2
- KZGXEJKMJNLRSF-UHFFFAOYSA-N Astragenol Natural products CC(C)(O)C1CCC(C)(O1)C2C(O)CC3(C)C4CC(O)C5(C)C(C)(C)C(O)CCC5(C)C4=CCC23C KZGXEJKMJNLRSF-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- 239000012429 reaction media Substances 0.000 abstract 1
- 230000035484 reaction time Effects 0.000 abstract 1
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 abstract 1
- QMNWISYXSJWHRY-YLNUDOOFSA-N astragaloside IV Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)[C@H]4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C[C@H]3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-YLNUDOOFSA-N 0.000 description 8
- QMNWISYXSJWHRY-BCBPIKMJSA-N astragaloside IV Natural products CC(C)(O)[C@@H]1CC[C@@](C)(O1)[C@H]2[C@@H](O)C[C@@]3(C)[C@@H]4C[C@H](O[C@@H]5O[C@H](CO)[C@H](O)[C@@H](O)[C@H]5O)[C@H]6C(C)(C)[C@H](CC[C@@]67C[C@@]47CC[C@]23C)O[C@@H]8OC[C@@H](O)[C@H](O)[C@H]8O QMNWISYXSJWHRY-BCBPIKMJSA-N 0.000 description 8
- PFKIBRPYVNVMRU-UHFFFAOYSA-N cyclosieversioside F Natural products CC(C)(O)C1COC(C)(C1)C2C(O)CC3(C)C4CC(OC5OC(CO)C(O)C(O)C5O)C6C(C)(C)C(CCC67CC47CCC23C)OC8OCC(O)C(O)C8O PFKIBRPYVNVMRU-UHFFFAOYSA-N 0.000 description 8
- 238000002390 rotary evaporation Methods 0.000 description 7
- 239000012071 phase Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000006136 alcoholysis reaction Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241001061264 Astragalus Species 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 239000009636 Huang Qi Substances 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- BIGPRXCJEDHCLP-UHFFFAOYSA-N ammonium bisulfate Chemical compound [NH4+].OS([O-])(=O)=O BIGPRXCJEDHCLP-UHFFFAOYSA-N 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000006533 astragalus Nutrition 0.000 description 1
- 229940107666 astragalus root Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
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- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
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- 238000001228 spectrum Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 210000004233 talus Anatomy 0.000 description 1
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- 102000055501 telomere Human genes 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
- C07J53/004—3 membered carbocyclic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention discloses a method for preparing cycloastragenol by degrading astragaloside, which is a method for preparing cycloastragenol by degrading astragaloside in a mixed medium formed by fatty alcohol-organic solvent by using solid acid which is slightly soluble in a reaction medium as a catalyst. In particular, the method takes astragaloside as a raw material, takes fatty alcohol as a degradation reagent in a medium formed by fatty alcohol-organic solvent, and degrades the glycosidic bond of the astragaloside under the catalysis of solid acid to remove xylosyl and glucosyl to obtain the cycloastragaloside. The degradation reaction condition is mild, the defect that the generated cycloastragenol is further converted into the astragenol or other byproducts is avoided, and the yield of the cycloastragenol can generally reach more than 50 percent. The method has the advantages of simple operation steps, short degradation reaction time, high product purity and low preparation cost, and is suitable for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a method for preparing cycloastragenol by degrading astragaloside.
Background
Astragalus root has been used as a traditional important Chinese medicine, and the medicine has been used for more than two thousand years so far. It has effects of strengthening body resistance, consolidating constitution, invigorating middle warmer, and invigorating qi. Astragaloside IV is the most main saponin substance in radix astragali, and has effects of enhancing organism immunity, improving organism disease resistance, resisting fatigue, protecting liver, eliminating in vivo free radical and inhibiting osteoclast. The content of astragaloside is an important index for judging the quality of the traditional Chinese medicinal materials of astragalus at present.
The astragaloside IV can be degraded into cycloastragaloside easily absorbed and utilized by intestinal flora in vivo, and the molecular mass and steric hindrance of the cycloastragaloside IV are smaller than those of astragaloside IV, and the cycloastragaloside IV has relatively good lipid solubility, and is easily absorbed by organism through cell membrane. Related researches report that cycloastragenol can be used as a telomerase activator, delay telomere shortening, increase the division frequency of cells and effectively inhibit the senescence of the cells. Therefore, the cycloastragenol has good application prospect in the aspect of anti-aging.
The currently reported methods for preparing cycloastragenol from astragaloside IV are mainly three conditions, namely an enzymolysis method, a Smith degradation method, an acid hydrolysis method and the like. 1) The Chinese invention discloses the patent: CN 105566434A; CN 105734109A; CN 106011213A; CN 107058445A; CN 111849959A; the document CN111893158A and the like mainly utilizes enzyme catalysis to prepare the cycloastragenol. Although the enzymatic hydrolysis method has high conversion rate, the requirements on reaction conditions are harsh, the steps are complicated, the preparation period is long, and the large-scale preparation is not facilitated. 2) The Chinese invention discloses the patent: CN 13880910B; documents such as CN106083979A disclose that cycloastragenol is prepared by Smith degradation by oxidation-reduction method, but the preparation process requires oxidation-reduction reaction using oxidant and reductant, and the number of preparation steps is too many, and the practicability is not high. 3) The Chinese invention discloses the patent: CN 102030799A; CN 104817610A; CN1099942663A et al disclose the use of hydrochloric acid and sulfuric acid to perform acid hydrolysis on astragaloside IV to prepare cycloastragenol. The acid hydrolysis method is simple to operate and low in cost, and is the main method for preparing the cycloastragenol at present. However, cycloastragenol is very easy to be converted into byproduct astragenol under severe acidic conditions, the reaction conditions are difficult to control, and the yield is often low.
Disclosure of Invention
The invention aims to provide a method for preparing cycloastragenol by degrading astragaloside, which has the advantages of mild reaction conditions, higher yield and less byproducts.
The invention provides a method for preparing cycloastragenol by degrading astragaloside under the catalysis of solid acid, which takes the astragaloside as a raw material, takes hydrosulfate which is slightly soluble in a degradation medium as a solid acid catalyst, takes fatty alcohol such as methanol, absolute ethyl alcohol, n-propyl alcohol, n-butyl alcohol, ethylene glycol and the like as a degradation reagent, and degrades the astragaloside in a medium formed by the fatty alcohol and organic solvents such as tetrahydrofuran, dioxane, ethyl acetate, methyl tert-butyl ether and the like to obtain the cycloastragenol.
The invention selects the fatty alcohol-organic solvent mixed solvent as the degradation medium for preparing the cycloastragenol from the astragaloside, the solubility of the astragaloside in the fatty alcohol is relatively high, the selected organic solvent also has certain solubility to the astragaloside, and the solubility of the astragaloside in the degradation medium is increased. Meanwhile, because the bisulfate is slightly soluble in fatty alcohol, the solubility of the solid acid in the degradation medium can be controlled by adjusting the composition or the proportion of the degradation medium, the hydrogen ion concentration and the catalytic capability of the degradation reaction are changed, and the degradation of the astragaloside IV is favorably converted into the cycloastragaloside IV. The degradation medium contains a large amount of fatty alcohol, the degradation is mainly realized by alcoholysis, the reaction is mild, and the excessive hydrolysis of the astragaloside in the water medium is avoided.
The reaction formula is as follows:
the method comprises the following specific operation steps:
1) selecting fatty alcohol and organic solvent to form an astragaloside degradation medium, adding astragaloside and solid acid into the degradation medium, stirring and reacting in a water bath at 50-90 ℃, tracking the reaction by using a high performance liquid chromatography, and stopping the reaction after the astragaloside raw material is completely disappeared to obtain a degradation liquid;
2) cooling and filtering the obtained degradation liquid, neutralizing the filtrate with a dilute alkali solution, removing the organic solvent, extracting the residue with an extractant, drying, removing the solvent to obtain a crude product of cycloastragenol, and purifying by column chromatography to obtain high-purity cycloastragenol;
the solid acid is bisulfate.
The mass-volume ratio of the astragaloside to the solid acid and the degradation medium is 1g:10-100g: 100-500 mL, preferably 1g:20-30g:250-500 mL.
The content of fatty alcohol in the degradation medium is more than 10%.
The aliphatic alcohol is methanol, absolute ethyl alcohol, n-propyl alcohol, n-butyl alcohol or ethylene glycol; methanol or absolute ethanol is preferred, and the content is preferably 30-50%.
The organic solvent is tetrahydrofuran, dioxane, ethyl acetate or methyl tert-butyl ether, etc.
The solid acid is hydrogen sulfate such as KHSO4、NaHSO4、(NH4)HSO4Etc., preferably sodium bisulfate, and function as a catalyst.
The extractant used in the step (2) is ethyl acetate or dichloromethane.
The column chromatography purification in the step (2) adopts 100-200-mesh silica gel as a stationary phase and dichloromethane-methanol mixed solution as a mobile phase for purification; the volume ratio of the dichloromethane to the methanol is 19: 1.
Compared with the prior art, the invention has the beneficial effects that:
in the existing literature reports, the preparation of the cycloastragenol is realized by hydrolyzing the glycosidic bond of the astragaloside, and the method for preparing the cycloastragenol by alcoholysis of the glycosidic bond of the astragaloside is not reported.
Aiming at the defects of the common method for preparing the cycloastragenol, the invention establishes the method for preparing the cycloastragenol by degrading the astragaloside in a fatty alcohol-organic solvent mixed medium by using the solid acid as the catalyst, realizes the degradation reaction under the mild condition by changing the solubility of the catalyst in the medium, avoids the over reaction of the cycloastragenol under the violent condition, improves the stability of the cycloastragenol in the medium, and ensures that the yield is more than 50 percent and the purity is more than 95 percent. The preparation method has simple steps and low cost, and is suitable for industrial production.
Drawings
FIG. 1 shows high performance liquid chromatogram (HPLC-ELSD) of degraded astragaloside IV solution, purified cycloastragaloside IV and cycloastragaloside IV standard
FIG. 2 of cycloastragenol1H NMR (DMSO-d6) spectrum
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The technical scheme of the invention is further explained in detail through specific embodiments. These examples are not intended to limit the scope of the present invention.
Example 1
Adding 1g of astragaloside with the purity of 98% and 25g of sodium hydrogen sulfate into a mixed medium of 150mL of methanol and 150mL of tetrahydrofuran, stirring and reacting for 20 hours in a water bath at 60 ℃, cooling and filtering to obtain a filtrate, neutralizing the filtrate by using a dilute alkali solution, removing an organic solvent by rotary evaporation, adding water to 100mL, extracting for three times by using equal volume of ethyl acetate, combining the ethyl acetate, and drying by using anhydrous sodium sulfate. And removing ethyl acetate by rotary evaporation to obtain a crude product of the cycloastragenol. Then 100-mesh 200-mesh silica gel is used as a stationary phase, and a 19:1 dichloromethane-methanol mixed solution is used as a mobile phase for column chromatography purification, so that 0.33g of cycloastragenol is obtained, the yield is 52.7 percent, and the purity is 97.5 percent.
Example 2
In a mixed medium of 50mL of ethylene glycol and 200mL of ethyl acetate, 1g of astragaloside IV with the purity of 85% and 20g of potassium hydrogen sulfate are added, and the mixture is stirred and reacted for 12 hours in a water bath at the temperature of 90 ℃, cooled and filtered. The resulting filtrate was neutralized with a dilute alkali solution, and then 50mL of distilled water was added, separated with a separatory funnel, the aqueous phase was extracted three times with 100mL of ethyl acetate, and the ethyl acetate was combined and dried over anhydrous sodium sulfate. And removing ethyl acetate by rotary evaporation to obtain a crude product of the cycloastragenol. Then 100-mesh 200-mesh silica gel is used as a stationary phase, and a 19:1 dichloromethane-methanol mixed solution is used as a mobile phase for column chromatography purification, so that 0.28g of cycloastragenol is obtained, the yield is 50.5%, and the purity is 95.6%.
Example 3
Adding 1g of astragaloside with the purity of 98% and 20g of ammonium bisulfate into a mixed medium of 150mL of anhydrous ethanol and 150mL of dioxane, stirring and reacting in a water bath at 80 ℃ for 16 hours, cooling, filtering to obtain filtrate, neutralizing the filtrate with a dilute alkali solution, removing an organic solvent by rotary evaporation, adding water to 150mL, extracting with equal volume of ethyl acetate for three times, combining the ethyl acetate, and drying with anhydrous sodium sulfate. And removing ethyl acetate by rotary evaporation to obtain a crude product of the cycloastragenol. Then 100-mesh 200-mesh silica gel is used as a stationary phase, and a 19:1 dichloromethane-methanol mixed solution is used as a mobile phase for column chromatography purification, so that 0.34g of cycloastragenol is obtained, the yield is 54.9 percent, and the purity is 98.5 percent.
Example 4
Adding 1g of astragaloside with the purity of 98% and 30g of sodium hydrogen sulfate into a mixed medium of 400mL of methanol and 100mL of methyl tert-butyl ether, stirring and reacting for 24 hours in a water bath at 60 ℃, cooling and filtering to obtain a filtrate, neutralizing the filtrate by using a dilute alkali solution, removing an organic solvent by rotary evaporation, adding water to 150mL, extracting for three times by using equal volume of ethyl acetate, combining the ethyl acetate, and drying by using anhydrous sodium sulfate. And removing ethyl acetate by rotary evaporation to obtain a crude product of the cycloastragenol. Then 100-mesh 200-mesh silica gel is used as a stationary phase, and a 19:1 dichloromethane-methanol mixed solution is used as a mobile phase for column chromatography purification, so that 0.31g of cycloastragenol is obtained, the yield is 50.2%, and the purity is 98.8%.
Claims (10)
1. A method for preparing cycloastragenol by degrading astragaloside is characterized by comprising the following steps:
1) selecting fatty alcohol and organic solvent to form an astragaloside degradation medium, adding astragaloside and solid acid into the degradation medium, stirring and reacting in a water bath at 50-90 ℃, tracking the reaction by using a high performance liquid chromatography, and stopping the reaction after the astragaloside raw material is completely disappeared to obtain a degradation liquid;
2) cooling and filtering the obtained degradation liquid, neutralizing the filtrate with a dilute alkali solution, removing the organic solvent, extracting the residue with an extractant, drying, removing the solvent to obtain a crude product of cycloastragenol, and purifying by column chromatography to obtain high-purity cycloastragenol;
the solid acid is bisulfate.
2. The method for preparing cycloastragenol by degrading astragaloside as claimed in claim 1, wherein the mass-volume ratio of the astragaloside, the solid acid and the degradation medium is 1g:10-100g: 100-.
3. The method for preparing cycloastragenol by degrading astragaloside as claimed in claim 2, wherein the mass-volume ratio of the astragaloside, the solid acid and the degradation medium is 1g:20-30g:250-500 mL.
4. A process for the preparation of cycloastragenol by degradation with astragaloside according to claim 1, 2 or 3, wherein in the degradation medium: the fatty alcohol is methanol, anhydrous ethanol, n-propanol, n-butanol or ethylene glycol; the organic solvent is tetrahydrofuran, dioxane, ethyl acetate or methyl tert-butyl ether; the content of fatty alcohol in the degradation medium is more than 10%.
5. The method for preparing cycloastragenol by degrading astragaloside according to claim 4, wherein the aliphatic alcohol is methanol or absolute ethanol, and the content of the aliphatic alcohol in the degradation medium is 30-50%.
6. The method for preparing cycloastragenol by degradation of astragaloside according to claim 1, 2 or 3, wherein the hydrogen sulfate salt is KHSO4、NaHSO4Or (NH)4)HSO4。
7. The method for preparing cycloastragenol by degrading astragaloside according to claim 6, wherein the bisulfate salt is NaHSO4。
8. The method for preparing cycloastragenol by degradation of astragaloside according to claim 1, 2 or 3, wherein the extractant used in step (2) is ethyl acetate or dichloromethane.
9. The method for preparing cycloastragenol by degrading astragaloside according to claim 1, 2 or 3, wherein the column chromatography purification in step (2) is performed by using 100-200 mesh silica gel as a stationary phase and using a dichloromethane-methanol mixed solution as a mobile phase.
10. The method for preparing cycloastragenol by degrading astragaloside according to claim 9, wherein the volume ratio of dichloromethane to methanol is 19: 1.
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