CN100390192C - Method for preparing monomer of ginsenoside and aglycon in low polarity through alkaline hydrolysis of natural ginsenoside - Google Patents
Method for preparing monomer of ginsenoside and aglycon in low polarity through alkaline hydrolysis of natural ginsenoside Download PDFInfo
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- CN100390192C CN100390192C CNB031340903A CN03134090A CN100390192C CN 100390192 C CN100390192 C CN 100390192C CN B031340903 A CNB031340903 A CN B031340903A CN 03134090 A CN03134090 A CN 03134090A CN 100390192 C CN100390192 C CN 100390192C
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- ginsenoside
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- alkaline hydrolysis
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Abstract
The present invention relates to a method for preparing low polar monomeric ginsenosides 20(S)-Rg3, 20(S)-Rh2, 20(S)-Rh1, 20(S)-protopanoxadiol or 20(S)-protopanaxatriol from natural ginsenosides. The present invention utilizes inert gas protection and free radical inductive agents to provide favorable condition for the alkaline hydrolysis of natural ginsenosides, and thereby, the present invention reduces reaction temperature, increases reactive selectivity, quickens reaction speed, and solves the problem of the directional preparation of low polar ginsenosides; the method has the advantages of simplicity, convenience and low cost; by the control of raw materials and reaction condition, the present invention can realize batch preparation of target low polar ginsenoside monomers and satisfy the requirement of medicine source.
Description
Technical field:
The present invention relates to method, particularly relate to alkaline hydrolysis and prepare the low polarity ginsenoside 20 (S) of monomer-Rg by low polarity ginsenoside of natural ginseng saponin(e preparation and aglycon thereof
3, 20 (S)-Rh
2, 20 (S)-Rh
1, 20 (S)-protopanoxadiols or 20 (S)-Protopanaxatriols method.
Background technology:
Studies show that low polarity ginsenoside have antitumor and immunoregulation effect, microcirculation improvement effect, regulate digestive function, calm the nerves, multiple biological activitys such as anti-ageing, anti-anxiety, prevention of digestive tract ulcers, raising quality of life, memory and learning capacity.But the low content of polarity ginsenoside in genseng is very little.Therefore, the production method of low polarity genseng soap receives much attention always.
The method of low polarity ginsenoside of preparation at present and aglycon thereof has biotransformation method (CN1229086A, CN01133410.X, CN02132403.4), High Temperature High Pressure alkali hydrolysis method (CN1225366A), high temperature alkaline solution solution (CN1293198A), acid-hydrolysis method (CN1243128A), acid catalysis pyrolysis method (CN02144780.2) and synthesis method (JP8-208688, KR NO.95-7250).
Be subjected to the restriction of enzyme selectivity and compound dissolution degree, biotransformation method is only applicable to the low polarity saponin of batch preparations 3-OH free such as C-K, C-Y, Mc and Mx.
Acid hydrolyzation intermediate product complexity, end product are the panoxadiol of side chain cyclisation and the compound of C-20 deshydroxy, rather than true aglycon, and product does not have the branch of major-minor, product separation and purification difficulty.As ginsenoside Rb
1, Rb
2, Rb
3, Rc and Rd → 20 (S)-Rg
3, 20 (R)-Rg
3, Rk
1, Rg
5→ 20 (S)-Rh
2, 20 (R)-Rh
2, Rk
2, Rh
3→ panoxadiol, 20-alkene-protopanoxadiol.
In the basic hydrolysis, the conversion route of saponin(e is: 20C-O desugar → 3C-O substep desugar, and as ginsenoside Rb
1, Rb
2, Rb
3, Rc and Rd → 20 (S)-Rg
3→ 20 (S)-Rh
2→ protopanoxadiol; The product retention of configuration is constant, and product is simple relatively.But it is very slow to be reflected at reaction below 100 ℃, generally temperature of reaction is increased to more than 200 ℃ with fast reaction speed.The temperature of reaction height brings many difficulties to actual production, and reaction is difficult to rest on a certain intermediate product, and the product dereliction branch that takes second place is unfavorable for Rg
3Or Rh
2Orientation preparation.When selecting for use the high boiling point Fatty Alcohol(C12-C14 and C12-C18) to be solvent in addition,, cause environmental pollution and cost to rise because of solvent can not reclaim.
The technology contents of invention:
The purpose of this invention is to provide a kind of can directly the degraded by the natural ginseng saponin(e simply, conveniently, low-costly and in high volume and prepare the low polarity ginsenoside 20 (S) of monomer-Rg
3, 20 (S)-Rh
2, 20 (S)-Rh
1, 20 (S)-protopanoxadiols or 20 (S)-Protopanaxatriols method, comprise alkaline hydrolysis and collect step that it is characterized in that: the degraded of natural ginseng saponin(e is under protection of inert gas, contains in the alkali organic solvent of radical inducer and carry out.Wherein:
The natural ginseng saponin(e refers to diol type ginsenoside Rb
1, Rb
2, Rb
3, Rc, Rd and triol type ginsenoside Re, Rf, Rg
1, Rg
2The concentration of natural ginseng saponin(e is 0.005～0.1mol/L, is good with 0.03～0.05mol/L; The product of diol type ginsenoside is 20 (S)-Rg
3, 20 (S)-Rh
2Or 20 (S)-protopanoxadiols, the product of triol type ginsenoside is 20 (S)-Rh
1, 20 (S)-Protopanaxatriols.
The protectiveness rare gas element is nitrogen, carbonic acid gas, helium, argon gas, neon etc.
The radical inducer is alkyl peroxide, acyl peroxide, azo-compound, alkyl peroxide, percarboxylate etc., as ditertiary butyl peroxide, benzoyl peroxide, Diisopropyl azodicarboxylate, tertbutyl peroxide etc.; Be good with tertbutyl peroxide or benzoyl peroxide wherein, consumption is 0.01～0.2mol/L.
Alkali is basic metal, alkalimetal oxide, alkali metal hydroxide or low-carbon (LC) sodium alkoxide, as sodium Metal 99.5, potassium metal, sodium oxide, potassium oxide, sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate etc., consumption is 0.02～2mol/L, is good with 1～2mol/L.
Organic solvent is the high boiling point Fatty Alcohol(C12-C14 and C12-C18), and as the low molecular poly that propyl carbinol, ethylene glycol, propylene glycol, butyleneglycol, glycerol, normal temperature are in a liquid state, the wherein recyclable utilization of propyl carbinol is carried out but be reflected in the autoclave.
Degradation temperature is 160～180 ℃, degradation time 1～5 hour.
The present invention is directly degraded by the natural ginseng saponin(e and prepares in the method for low polarity ginsenoside of monomer and aglycon thereof, and final collection process is: the reaction solution after the degraded is collecting precipitation after big water gaging dilution; Or directly remove water miscible solvent and water-soluble degraded product obtains target product through macroporous adsorbent resin; Or,, and after water miscible solvent and water-soluble degraded product are removed in washing, obtain the low polarity saponin of target with the low polarity saponin of ethyl acetate, propyl carbinol or chloroform extraction through the acid neutralization.When being solvent with the propyl carbinol, but capable more above-mentioned processing behind the reclaim under reduced pressure propyl carbinol.
The present invention is directly degraded by the natural ginseng saponin(e and prepares in the method for low polarity ginsenoside of monomer and aglycon thereof, by the control of raw material and reaction conditions, can make reaction pair hang down polarity ginsenoside 20 (S)-Rg
3, 20 (S)-Rh
2, 20 (S)-Rh
1, 20 (S)-protopanoxadiols or 20 (S)-Protopanaxatriols have high selectivity, help realizing the preparation of the low polarity ginsenoside monomer of target.
The invention provides a kind of can be simply, convenient, prepare the low polarity ginsenoside 20 (S) of monomer-Rg by the direct alkaline hydrolysis of natural ginseng saponin(e low-costly and in high volume
3, 20 (S)-Rh
2, 20 (S)-Rh
1, 20 (S)-protopanoxadiols or 20 (S)-Protopanaxatriols method, significantly reduced alkali hydrolysis method to temperature of reaction, improved reaction selectivity, accelerated speed of response, solved the difficult problem of the directed degraded of ginsenoside.This technology is simple and convenient, cost is low, the rate of recovery high (aglycon yield 〉=90%), quality good (content 〉=80%).
Embodiment:
Embodiment 1
5g panoxadiol type saponin(e is dissolved in the 100ml alkalescence propyl carbinol (containing NaOH5g, benzoyl peroxide 0.1g), under 160 ℃ of temperature (about 0.14MPa), nitrogen protection condition, stirs degraded 3h; Reaction solution obtains resistates 3.34g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly ginsenoside 20 (S)-Rg through check
3(content 〉=80%) and a small amount of ginsenoside 20 (S)-Rh
2With 20 (S)-protopanoxadiols.
Embodiment 2
5g panoxadiol type saponin(e is dissolved in the 100ml alkalescence propyl carbinol (containing metal sodium 8g, benzoyl peroxide 1g), under 180 ℃ of temperature (about 0.15MPa), nitrogen protection condition, stirs degraded 5h; Reaction solution obtains resistates 2.4g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly 20 (S)-protopanoxadiols (content 〉=80%) and a small amount of ginsenoside 20 (S)-Rg through check
3With 20 (S)-Rh
2
Embodiment 3
5g panoxadiol type saponin(e is dissolved in the 100ml alkalescence propyl carbinol (containing sodium methylate 5g, benzoyl peroxide 0.5g), under 170 ℃ of temperature (about 0.145MPa), nitrogen protection condition, stirs degraded 4h; Reaction solution obtains resistates 2.9g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly ginsenoside 20 (S)-Rh through check
2(content 〉=80%) and a small amount of ginsenoside 20 (S)-Rg
3With 20 (S)-protopanoxadiols.
Embodiment 4
5g panoxadiol type saponin(e is dissolved in the 100ml alkalescence glycerol (containing NaOH 5g, benzoyl peroxide 0.1g), under 160 ℃ of temperature, nitrogen protection condition, stirs degraded 3h; Reaction solution is collecting precipitation after neutralization (2mol/L HCl), water dilution (1000mL); Precipitation obtains resistates 3.12g through washing and drying.Be mainly ginsenoside 20 (S)-Rh through check
2(content 〉=80%) and a small amount of ginsenoside 20 (S)-Rg
3With 20 (S)-protopanoxadiols.
Embodiment 5
The 5g ginsenoside Re is dissolved in the 100ml alkalescence propyl carbinol (containing NaOH 5g, benzoyl peroxide 0.5g), under 160 ℃ of temperature (about 0.14MPa), nitrogen protection condition, stirs degraded 3h; Reaction solution obtains resistates 3.5g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly ginsenoside 20 (S)-Rg through check
2(content 〉=80%) and a small amount of ginsenoside 20 (S)-Rh
1With 20 (S)-Protopanaxatriols.
Embodiment 6
The 5g ginsenoside Rg
1, be dissolved in the 100ml alkalescence propyl carbinol (containing NaOH 5g and tertbutyl peroxide 0.5g), under 160 ℃ of temperature (about 0.14MPa), nitrogen protection condition, stir degraded 3h; Reaction solution obtains resistates 3.5g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly ginsenoside 20 (S)-Rh through check
1(content 〉=80%) and a small amount of 20 (S)-Protopanaxatriols.
Embodiment 7
5g panoxatriol type saponin(e is dissolved in the 100ml alkalescence propyl carbinol (containing metal sodium 0.5g and tertbutyl peroxide 0.5g), under 170 ℃ of temperature (about 0.15MPa), nitrogen protection condition, stirs degraded 5h; Reaction solution obtains resistates 3.4g after neutralization (2mol/L HCl), washing (100mL * 5), anhydrous sodium sulfate drying, decompression steam propyl carbinol.Be mainly 20 (S)-protopanoxadiols (content 〉=80%) and a small amount of ginsenoside 20 (S)-Rg through check
2With 20 (S)-Rh
1
Embodiment 8
5g panoxadiol type saponin(e is dissolved in the 100ml alkalescence glycerol (containing NaOH 8g and tertbutyl peroxide 0.5g), under 160 ℃ of temperature, nitrogen protection condition, stirs degraded 3h; Reaction solution is collecting precipitation after neutralization (2mol/L HCl), water dilution (1000mL); Precipitation obtains resistates 3.22g through washing and drying.Be mainly ginsenoside 20 (S)-Rh through check
2(content 〉=80%) and a small amount of ginsenoside 20 (S)-Rg
2With 20 (S)-Protopanaxatriols.
Embodiment 9
5g ginsenoside Rb
1, be dissolved in the 100ml glycerol and (contain NaOH 8g and tertbutyl peroxide 0.5g), under 170 ℃ of temperature, nitrogen protection condition, stir degraded 5h; Reaction solution thin up (1000mL) back collecting precipitation; Precipitation obtains resistates 2.58g through washing and drying.Be mainly 20 (S)-protopanoxadiols (content 〉=80%) through check.
Embodiment 10
The 5g ginsenoside Re is dissolved in the 100ml glycerol and (contains NaOH 8g and tertbutyl peroxide 0.5g), under 170 ℃ of temperature, nitrogen protection condition, stirs degraded 4h; Reaction solution thin up (1000mL) back collecting precipitation; Precipitation obtains resistates 2.79g through washing and drying.Be mainly 20 (S)-Protopanaxatriols (content 〉=80%) through check.
Claims (10)
1. an alkaline hydrolysis natural ginseng saponin(e prepares the method that monomer hangs down polarity ginsenoside and aglycon thereof, and described natural ginseng saponin(e refers to diol type ginsenoside Rb
1, Rb
2, Rb
3, Rc, Rd, triol type ginsenoside Re, Rf, Rg
1, or Rg
2, low polarity ginsenoside of described monomer and aglycon thereof refer to 20 (S)-Rg
3, 20 (S)-Rh
2, 20 (S)-protopanoxadiols, 20 (S)-Rh
1, or 20 (S)-Protopanaxatriols, comprise degraded and collect step that it is characterized in that: the degraded of natural ginseng saponin(e is under protection of inert gas, contains in the alkali organic solvent of radical inducer and carry out; Described radical inducer is alkyl peroxide, acyl peroxide, azo-compound, alkyl peroxide or percarboxylate, and consumption is 0.01～0.2mol/L; Described protectiveness rare gas element is nitrogen, carbonic acid gas, helium, argon gas, neon.
2. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to the described alkaline hydrolysis natural ginseng of claim 1 saponin(e, it is characterized in that: described radical inducer is benzoyl peroxide or tertbutyl peroxide.
3. the method for preparing low polarity ginsenoside of monomer and aglycon thereof according to claim 1 or 2 described alkaline hydrolysis natural ginseng saponin(es, it is characterized in that: described alkali is basic metal, alkalimetal oxide, alkali metal hydroxide or low-carbon (LC) sodium alkoxide, and consumption is 0.02～2mol/L.
4. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to the described alkaline hydrolysis natural ginseng of claim 3 saponin(e, it is characterized in that: the consumption of described alkali is 1～2mol/L.
5. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to claim 1 or 2 described alkaline hydrolysis natural ginseng saponin(es, it is characterized in that: the low molecular poly that described organic solvent propyl carbinol, ethylene glycol, propylene glycol, butyleneglycol, glycerol or normal temperature are in a liquid state.
6. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to claim 1 or 2 described alkaline hydrolysis natural ginseng saponin(es, it is characterized in that: the concentration of described natural ginseng saponin(e is 0.005～0.1mol/L.
7. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to the described alkaline hydrolysis natural ginseng of claim 6 saponin(e, it is characterized in that: the concentration of described natural ginseng saponin(e is 0.03～0.05mol/L.
8. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to claim 1 or 2 described alkaline hydrolysis natural ginseng saponin(es, it is characterized in that: described degradation temperature is 160～180 ℃, degradation time 1～5 hour.
9. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to claim 1 or 2 described alkaline hydrolysis natural ginseng saponin(es, it is characterized in that described collection process is: the reaction solution after the degraded is collecting precipitation after big water gaging dilution; Or directly remove water miscible solvent and water-soluble degraded product through macroporous adsorbent resin; Or,, and after water miscible solvent and water-soluble degraded product are removed in washing, obtain low polarity ginsenoside of monomer and aglycon thereof with ethyl acetate, propyl carbinol or chloroform extraction through the acid neutralization.
10. prepare the method for low polarity ginsenoside of monomer and aglycon thereof according to the described alkaline hydrolysis natural ginseng of claim 9 saponin(e, it is characterized in that: when with the propyl carbinol being the degraded solvent, behind the reclaim under reduced pressure propyl carbinol, regather.
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| CN100390192C true CN100390192C (en) | 2008-05-28 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101671384B (en) * | 2009-10-12 | 2012-05-02 | 玉溪市维和生物技术有限责任公司 | Method for preparing ginsenoside Rh1 |
| CN106957351A (en) * | 2016-01-08 | 2017-07-18 | 杨丽娟 | The preparation method of 20 (S)-protopanoxadiols |
| CN107200768B (en) * | 2017-06-15 | 2018-05-01 | 吉林大学 | A kind of method for preparing phoenix celestial being terpene tetrol aglycon |
| CN109824750A (en) * | 2019-03-19 | 2019-05-31 | 云南三七科技有限公司 | A kind of preparation method of the rare saponin(e of ginseng |
| CN113637044B (en) * | 2021-05-08 | 2023-11-03 | 中国人民解放军海军军医大学 | Method for preparing protopanoxadiol and protopanaxatriol |
| CN114702541B (en) * | 2022-01-23 | 2022-12-02 | 吉林农业大学 | Large-scale preparation method of compound 20 (S) -protopanaxatriol PPT |
| CN114702540A (en) * | 2022-01-23 | 2022-07-05 | 吉林农业大学 | Novel preparation method and application of compound 20(S) -protopanaxadiol PPD |
| CN115260269B (en) * | 2022-06-28 | 2024-04-05 | 成都大学 | Composition containing ginseng secondary glycoside and aglycone thereof, preparation method and application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1225366A (en) * | 1998-02-05 | 1999-08-11 | 大连天马制药有限公司 | Method for preparing 20(S)-ginsenoside-RH2, medicinal compositions therewith and use thereof |
| CN1243128A (en) * | 1998-07-28 | 2000-02-02 | 白求恩医科大学基础医学院科技开发公司 | Semisynthesizing method for 20(S)-ginsenoside Rg3, and use in medicine |
| CN1293198A (en) * | 2000-10-10 | 2001-05-02 | 白求恩医科大学基础医学院科技开发公司 | Process for preparing rare-sinsenoside |
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2003
- 2003-09-28 CN CNB031340903A patent/CN100390192C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1225366A (en) * | 1998-02-05 | 1999-08-11 | 大连天马制药有限公司 | Method for preparing 20(S)-ginsenoside-RH2, medicinal compositions therewith and use thereof |
| CN1243128A (en) * | 1998-07-28 | 2000-02-02 | 白求恩医科大学基础医学院科技开发公司 | Semisynthesizing method for 20(S)-ginsenoside Rg3, and use in medicine |
| CN1293198A (en) * | 2000-10-10 | 2001-05-02 | 白求恩医科大学基础医学院科技开发公司 | Process for preparing rare-sinsenoside |
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