CN101838303A - Preparation method of glycyrrhetinic acid - Google Patents
Preparation method of glycyrrhetinic acid Download PDFInfo
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- CN101838303A CN101838303A CN201010192841.9A CN201010192841A CN101838303A CN 101838303 A CN101838303 A CN 101838303A CN 201010192841 A CN201010192841 A CN 201010192841A CN 101838303 A CN101838303 A CN 101838303A
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- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 title claims abstract description 126
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 229960003720 enoxolone Drugs 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 46
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 43
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims abstract description 25
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960004949 glycyrrhizic acid Drugs 0.000 claims abstract description 25
- 235000019410 glycyrrhizin Nutrition 0.000 claims abstract description 25
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- 239000001685 glycyrrhizic acid Substances 0.000 claims abstract description 24
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- 239000012043 crude product Substances 0.000 claims abstract description 16
- 239000000047 product Substances 0.000 claims abstract description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 12
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- ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 description 2
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Abstract
The invention relates to a preparation method of glycyrrhetinic acid, which comprises the steps of: hydrolyzing glycyrrhizic acid crude products as raw materials by adding dilute sulphuric acid to generate glycyrrhetinic acid, wherein microwave radiation is adopted for heating in the hydrolyzation process which is carried out in a closed container; eluting hydrolyzed products by using chloroform, and rotationally evaporating the chloroform to obtain the glycyrrhetinic acid crude products. Reaction is carried out under different conditions, and the conversion rate can reach 60-90 percent. The invention has the advantages of simple operation, time saving, high conversion rate and low requirements on purity of the glycyrrhizic acid crude products as the raw materials. The preparation method can be applied to preparing the glycyrrhetinic acid.
Description
Technical field
The present invention relates to a kind of preparation method of glycyrrhetinic acid, belong to the applied chemistry field.
Background technology
Radix Glycyrrhizae acids medicine in human body through the hydrochloric acid in gastric juice hydrolysis or in liver GRD beta-glucuronidase be decomposed into glycyrrhetinic acid, again in liver sausage circulation in intestines the bacterium agency part generate 3-table-glycyrrhetinic acid and a small amount of 3-dehydrogenation glycyrrhetinic acid and pharmaceutical activity take place.So the effect of Radix Glycyrrhizae acids medicine comes down to the effectiveness of glycyrrhetinic acid performance.Utilize glycyrrhetinic acid that the BEL-7402 human liver cancer cell is experimentized, measure its restraining effect cancer cell multiplication.The result shows that glycyrrhetinic acid and Potenlini all have the effect that suppresses human liver cancer cell propagation and induce differentiation, and under the condition of equivalence, glycyrrhetinic acid is lower 40 times than Potenlini desired concn.Glycyrrhetinic acid is present in the Radix Glycyrrhizae, can be produced by the Potenlini hydrolysis, and its molecular formula is C
30H
46O
4, relative molecular mass 470.67 belongs to pentacyclic triterpenoid, and white crystal, has different optical isomers: 18 α-glycyrrhetinic acid and 18 β-glycyrrhetinic acid by fusing point 289-291 ℃.Modern study shows that glycyrrhetinic acid has many-sided effects such as anti-inflammatory, antiulcer agent, antiviral (hepatitis virus, virus of AIDS etc.), reducing blood-fat, anti-curing oncoma, promotion absorption of insulin.Glycyrrhetinic acid and all medicines mutually combine, and make the derivative of glycyrrhetinic acid, reach to keep or to improve the purpose that original drug effect can be eliminated original drug side effect again.In future, glycyrrhetinic acid is expected to the medicine of synthetic new antitumor and anti-AIDS.In addition, glycyrrhetinic acid and derivative thereof can be used for natural antiseptic agent, natural toner and natural thickener, in food, makeup, household chemicals field application are arranged also, and along with the carrying out of studying, these application will have more wide prospect.The research and development of glycyrrhetinic acid and derivative thereof are one of focuses of various countries scientist research in recent decades, present unprecedented research boom.
Extracting Potenlini from Radix Glycyrrhizae, to prepare glycyrrhetinic acid be a successive process.At first, Radix Glycyrrhizae mainly is decomposed into the macromole Potenlini, has the small portion glycyrrhetinic acid to produce simultaneously by dissolving; Under the effect of soda acid cracking and catalyzing or enzymatic, Potenlini is decomposed into glycyrrhetinic acid then.No matter be by acid-base catalysis or enzymatic reaction, the extraction Potenlini prepares glycyrrhetinic acid from Radix Glycyrrhizae all needs to separate step through the glucoside bond cleavage of Potenlini, thereby prepares glycyrrhetinic acid.
At present, the preparation method of glycyrrhetinic acid has three kinds: acidifying cracking, alkalization cracking and enzymatic reaction.The acidifying cracking promptly makes its hydrolysis obtain the glycyrrhetinic acid crude product by add acid in Potenlini or glycyrrhizin (glycyrrhetate), add then that chloroform is molten to be carried, again through alumina column chromatography or dissolve with ethanol, after add elutriation behind the activated carbon decolorizing and go out crystallization and be prepared into the glycyrrhetinic acid product.Theoretically, Potenlini is hydrolyzed under acidic conditions can obtain glycyrrhetinic acid, but its hydrolytic process is difficult to finish under the actual normal temperature and pressure, must be in Potenlini hydrolysis smoothly under the suitable heating and pressurizing condition.The hydrolysis of Potenlini, long reaction time violent under the heating and pressurizing situation, glycyrrhetinic acid because of condition occur easily dehydration, ring and, variation such as two key transfers, just can obtain glycyrrhetinic acid to such an extent as to have only under the certain conditions it is hydrolyzed.Ceng Qihua (Ceng Qihua, Zun Yi college of education journal, 2006,8 (1), 62-64) once adopted acidization with an amount of Potenlini and 5%H
2SO
4Solution places the pressure-resistant seal sleeve pipe, places 16 hours down at 1200 ℃, gets the glycyrrhetinic acid crude product with chloroform extraction behind the naturally cooling, gets the glycyrrhetinic acid crystal with the Glacial acetic acid recrystallization then, yield (considering with Radix Glycyrrhizae) about 4%.Wang Peixi (Wang Peixi, the chemical goods scientific and technological information, 1993,12-16) grade adds 5%H with monoammonium glycyrrhizinate
2SO
4In the solution, be heated with stirring to nearly boiling, back hydrolysis 15 hours, filter wash the glycyrrhetinic acid crude product.Through recrystallization decolour content at the glycyrrhetinic acid more than 92%.Total recovery is about 0.5% (in Radix Glycyrrhizae).Zhao Jianyu (Zhao Jianyu, General Armament Department's medical journal, 1999,1 (1): 24-25) with 4g monoammonium glycyrrhizinate and 5mL75% ethanolic soln and 35mL15%H
2SO
4The heating of solution asbestos process furnace, stirring and refluxing 6 hours is separated out white precipitate, and suction filtration is washed to the neutral glycyrrhetinic acid crude product that gets.Get the glycyrrhetinic acid crystal after purified, productive rate is 85.7%.So, when adopting the acidified water solution to extract glycyrrhetinic acid, though technological process is simple relatively, its processing parameter harshness, the process cycle is long, and productive rate is low, and the purity of glycyrrhetinic acid is not high yet.Potenlini is extracted in the alkalization cracking from Radix Glycyrrhizae to prepare the principle of glycyrrhetinic acid and flow process and acidifying cracking roughly the same.Under alkaline condition, further acidifying ability purification glycyrrhetinic acid, increased the complexity of technology.Zymin and bionic extraction method can be extracted glycyrrhetinic acid under comparatively gentle condition, its processing parameter is so harsh unlike the soda acid cracking, therefore, a lot of scholars begin to explore zymin or bionical method based on enzymatic reaction and extract Potenlini from Radix Glycyrrhizae and prepare glycyrrhetinic acid.But its main defective is complex technical process, and flow process and cycle are longer, complicated operation.And, increased the difficulty of extraction effect index evaluation owing to will consider pharmacology group effect and Chinese medicine pharmacokinetics.
Microwave technology is designed first by Randall and Booth when World War II and is used for military radar, the every field that then progressively enters human society.In recent ten years, microwave-assisted extracts the extraction of be widely used natural compounds and bioactive ingredients.Microwave technology has high-recovery, highly selective, rapid heating, be easy to temperature control and low solvent consumption, equipment size is less, the utilization of pollution-free energy source, reduce the pollution of refuse and product, but to the heat-sensitive substance rapid extraction, reduce its thermolysis effect, reduce the generation of by product, leaching process is capable of fast starting, therefore series of advantages such as process is simple can consider to be used for microwave technology is applied to the preparation of glycyrrhetinic acid.
Summary of the invention
The objective of the invention is to the deficiency that exists among the present glycyrrhetinic acid preparation method, propose a kind of novel method for preparing glycyrrhetinic acid.This method is raw material with the glycyrrhizic acid inclusion compound, under acidic conditions, by microwave heating, makes the Potenlini hydrolysis generate glycyrrhetinic acid in sealed vessel.Have experimental implementation easy, save time, advantage that transformation efficiency is high, and not high to the purity requirement of glycyrrhizic acid inclusion compound.
Technical scheme of the present invention is, with glycyrrhizic acid inclusion compound with put into encloses container after dilute sulphuric acid mixes, adopt the heating means of microwave radiation to prepare glycyrrhetinic acid.Heat in encloses container, can avoid the volatilization of acid, the acidity in the guarantee system has been saved stirring simultaneously.Carry out microwave radiation heating is a kind of inner heat-processed, and it is different from common external heating mode heat is delivered to inside by the material outside, but directly acts on medium molecule simultaneously, and whole material is heated simultaneously, promptly so-called " volume heating ".Adopt the present invention to prepare glycyrrhetinic acid, through high effective liquid chromatography for measuring content, transformation efficiency reaches 60～90% and does not wait under different condition.
The preparation method of glycyrrhetinic acid of the present invention may further comprise the steps:
(1) glycyrrhizic acid inclusion compound and concentration are to put into sealing micro-wave digestion jar after 1～10% dilute sulphuric acid mixes, and micro-wave digestion obtains clearing up product;
(2) will clear up product and carry with chloroform is molten, rotary evaporation falls chloroform, obtains the glycyrrhetinic acid crude product.
Above-mentioned Potenlini is cleared up the type of heating that uses and is microwave heating, and the digestion condition scope is 130～170 ℃, and the micro-wave digestion heating schedule is to be warming up to assigned temperature in 15 minutes, and the back kept 2～10 minutes.
In the said step (1), glycyrrhizic acid inclusion compound and dilute sulphuric acid blended liquid-solid ratio (mL/g) scope are 5: 1～30: 1; In the said step (2), chloroform is an analytical pure.
Compare with prior art, the present invention has the following advantages or positively effect:
1, the raw material glycyrrhizic acid inclusion compound that is used to prepare glycyrrhetinic acid does not need to make with extra care, and the crude product that glycyrrhizic acid content is lower also can reach very high transformation efficiency.
2, adopt carry out microwave radiation heating, the heating efficiency height, the reaction times is short, just can react fully in 30 minutes and carry out.
3, adopt airtight micro-wave digestion jar as reaction vessel, do not need reflux and whipping appts, simple to operate.
This glycyrrhetinic acid preparation method can be applied to the preparation of glycyrrhetinic acid.
Description of drawings
Fig. 1 is a glycyrrhizic acid inclusion compound liquid chromatography for measuring collection of illustrative plates, and Fig. 2 is a glycyrrhetinic acid sample liquid chromatography for measuring collection of illustrative plates.
Embodiment
Also the invention will be further described in conjunction with the accompanying drawings below by embodiment.
Embodiment 1
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 1% dilute sulphuric acid, liquid-solid ratio (mL/g) is 25: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 150 ℃ in 15 minutes, the back kept temperature 6 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency 73.78%.
Embodiment 2:
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 10% dilute sulphuric acid, liquid-solid ratio (mL/g) is 25: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 130 ℃ in 15 minutes, the back kept temperature 4 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency is 79.44%.
Embodiment 3:
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 5% dilute sulphuric acid, liquid-solid ratio (mL/g) is 30: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 150 ℃ in 15 minutes, the back kept temperature 10 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency 80.06%.
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 5% dilute sulphuric acid, liquid-solid ratio (mL/g) is 25: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 150 ℃ in 15 minutes, the back kept temperature 2 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency 91.38%.
Embodiment 5
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 5% dilute sulphuric acid, liquid-solid ratio (mL/g) is 20: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 170 ℃ in 15 minutes, the back kept temperature 10 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency 72.09%.
1, get 2g glycyrrhizic acid inclusion compound (glycyrrhizic acid content is about 18%) and mix with 4% dilute sulphuric acid, liquid-solid ratio (mL/g) is 5: 1, puts into sealing micro-wave digestion jar, micro-wave digestion.Heating schedule is: be warming up to 150 ℃ in 15 minutes, the back kept temperature 8 minutes.
2, will clear up product and carry with chloroform is molten, rotary evaporation promptly gets the glycyrrhetinic acid crude product after falling chloroform.Carry out assay, transformation efficiency 60.53%.
Claims (5)
1. the preparation method of a glycyrrhetinic acid is characterized in that may further comprise the steps:
(1) be to put into sealing micro-wave digestion jar after 1～10% dilute sulphuric acid mixes with glycyrrhizic acid inclusion compound and concentration, micro-wave digestion obtains clearing up product;
(2) will clear up product and carry with chloroform is molten, rotary evaporation falls chloroform, obtains the glycyrrhetinic acid crude product.
2. according to the preparation method of claim 1, it is characterized in that: Potenlini is cleared up the type of heating that uses and is microwave heating, and the digestion condition scope is 130～170 ℃, and the micro-wave digestion heating schedule is to be warming up to assigned temperature in 15 minutes, and the back kept 2～10 minutes.
3. according to the preparation method of claim 1 and 2, it is characterized in that: in the said step (1), glycyrrhizic acid inclusion compound and dilute sulphuric acid blended liquid-solid ratio (mL/g) scope are 5: 1～30: 1.
4. according to the preparation method of claim 1 and 2, it is characterized in that: in the said step (2), chloroform is an analytical pure.
5. according to the preparation method of claim 3, it is characterized in that: in the said step (2), chloroform is an analytical pure.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102786574A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal A substance, its preparation method, and its applications in medicines and healthcare products |
| CN102786573A (en) * | 2011-05-17 | 2012-11-21 | 中国医学科学院药物研究所 | Glycyrrhetinic acid crystal B substance, its preparation method, and its applications in medicines and healthcare products |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0739627A1 (en) * | 1994-06-21 | 1996-10-30 | Albrecht, Uwe, Dipl.-Dok. | Use of glycyrrhizinic acid and its metabolite (glycyrrhetinic acid) as active ingredient in the manufacture of a medicament for the treatment of malignant diseases (cancer) |
| CN1563073A (en) * | 2004-04-06 | 2005-01-12 | 南开大学 | Method for preparing enoxolone |
-
2010
- 2010-06-07 CN CN201010192841.9A patent/CN101838303A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0739627A1 (en) * | 1994-06-21 | 1996-10-30 | Albrecht, Uwe, Dipl.-Dok. | Use of glycyrrhizinic acid and its metabolite (glycyrrhetinic acid) as active ingredient in the manufacture of a medicament for the treatment of malignant diseases (cancer) |
| CN1563073A (en) * | 2004-04-06 | 2005-01-12 | 南开大学 | Method for preparing enoxolone |
Non-Patent Citations (2)
| Title |
|---|
| 《江西农业学报》 20080815 余方等 从甘草中提取甘草酸制备甘草次酸的研究进展 91～94 1-5 , 第08期 2 * |
| 《遵义师范学院学报》 20060228 曾启华 从甘草中提取甘草酸和甘草次酸的工艺研究 63-64页2.4和3.1节 1-5 第8卷, 第1期 2 * |
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