CN102731603A - Preparation method of panaxadiol and 20(R)-protopanaxadiol - Google Patents
Preparation method of panaxadiol and 20(R)-protopanaxadiol Download PDFInfo
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- CN102731603A CN102731603A CN2011100814735A CN201110081473A CN102731603A CN 102731603 A CN102731603 A CN 102731603A CN 2011100814735 A CN2011100814735 A CN 2011100814735A CN 201110081473 A CN201110081473 A CN 201110081473A CN 102731603 A CN102731603 A CN 102731603A
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Abstract
The invention relates to a preparation method of panaxadiol and 20(R)-protopanaxadiol, comprising the following steps of: using a Panax plant or its stem leaf's total saponin extract product or a total saponin extract product of a gynostemma pentaphylla plant as a raw material, performing acidic hydrolysis in a solvent, and carrying out separation and purification by column chromatography to obtain high-purity panaxadiol and 20(R)-protopanaxadiol. The method has the following advantages: the raw materials are easily available; reaction condition is mild; the cost is low; the product is easy to separate and purify; and the yield is high. In addition, the method is suitable for industrial production and is used to meet requirements of antineoplastic, anti-inflammatory and antidepressant medicinal resources.
Description
Technical field
The present invention relates to the preparation method of a kind of panoxadiol and 20 (R)-protopanoxadiol.
Background technology
Ginsenoside is the main bioactive ingredients in the panax species; Belonging to tetracyclic triterpenoid. the difference by chemical structure can be divided into protopanoxadiol type, Protopanaxatriol's type and oleanolic acid type 3 big classes with ginsenoside; In the panax species body, these ginsenosides are 20 (S) structure.Protopanoxadiol is the aglycon part of protopanoxadiol type saponin(e; Research shows: protopanoxadiol and verivate thereof have antitumor, anti-inflammatory; Multiple biological activitys such as antidepressant, immunomodulatory, microcirculation improvement, enhancing body immunizing power, memory; The while protopanoxadiol can be used for preparation and has multiple bioactive rare ginsenoside, and 20 (R)-protopanoxadiol activity are better than 20 (S)-protopanoxadiols, are necessary to prepare monomer whose and are used for furtheing investigate further.Panoxadiol is the product of protopanoxadiol side chain cyclisation, also can be used for preparation and has multiple bioactive rare ginsenoside.The total saponin extracts of first-selected panax species of the present invention or cauline leaf is a raw material, and existing research simultaneously shows that gynostemma plant contains more than 50 kind of genseng saponin constituent, and its total saponin extracts also can be used as raw material of the present invention and uses.
The method that bibliographical information prepares protopanoxadiol has acid-hydrolysis method, alkaline hydrolysis method and enzyme liberating method.The alkaline hydrolysis method can prepare 20 (S)-protopanoxadiols, but often needs HTHP, and reaction system usually needs specific gas shield, complicated operation, and cost is higher.The enzyme liberating method requires raw material diol type saponin content higher, and yield is low, long reaction time, and aftertreatment is complicated.It is high to ingredient requirement to add protectant acid-hydrolysis method, and its yield is low, cost is high, and product is the mixture of 20 (S)-protopanoxadiols and 20 (R)-protopanoxadiols, is difficult to purifying.Not seeing has bibliographical information to prepare the method for panoxadiol and 20 (R)-protopanoxadiol simultaneously.
Summary of the invention
For this reason, the invention provides a kind of can be simply, convenient, low-cost, be the method for feedstock production panoxadiol and 20 (R)-protopanoxadiol with the total saponin extracts of panax species or cauline leaf or the total saponin extracts of gynostemma plant in large quantities.Method of the present invention can be represented with following reaction formula:
Embodiment
Below, can further understand the present invention, but can not limit content of the present invention through specific embodiment.
Embodiment 1
Notoginseng haulm 10kg (available from Yunnan) is ground into Powdered (100-200 order), with 20kg 95% alcohol immersion 50 hours, filters; Filtrating concentrate the notoginseng haulm ethanol extraction, ethanol reclaims to reuse and soaks filter residue 5 times, final accumulative total pseudo-ginseng ethanol extraction 3.5kg; It is soluble in water, and with petroleum ether extraction twice, water intaking is used n-butanol extraction 5 times mutually; N-butanol layer concentrates, and gets notoginseng stem and leaf total saponin extract 1.5kg.
Embodiment 2
Get notoginseng stem and leaf total saponin extract 10g and be dissolved in the 100ml concentrated hydrochloric acid, sealing, room temperature stirred 80 hours, and reaction finishes.Filter, water concentrates the back and merges with filter residue with ethyl acetate extraction 2 times, and filter residue is suspended in the saturated sodium bicarbonate solution, stirring reaction 30 hours, reaction end.Filter, filter residue is through silica gel column chromatography, and petroleum ether-ethyl acetate solution gradient drip washing purifying gets panoxadiol 1.2g, and it is 95.6% that HPLC measures purity; 20 (R)-protopanoxadiol 350mg, it is 96.89% that HPLC measures purity.
Embodiment 3
Get notoginseng stem and leaf total saponin extract 10g and be dissolved in 100ml 50% sulfuric acid, room temperature stirred 24 hours, and reaction finishes.Filter, water concentrates the back and merges with filter residue with ethyl acetate extraction 2 times, and filter residue is suspended in the saturated sodium bicarbonate solution, stirring reaction 30 hours, reaction end.Filter, filter residue is through silica gel column chromatography, and petroleum ether-ethyl acetate solution gradient drip washing purifying gets panoxadiol 1.26g, and it is 95.2% that HPLC measures purity; 20 (R) protopanoxadiol 370mg, it is 97.23% that HPLC measures purity.
Embodiment 4
Get notoginseng stem and leaf total saponin extract 10g and be dissolved in 200ml 80% trifluoracetic acid, sealing, room temperature stirred 60 hours, and reaction finishes.Concentrating under reduced pressure is removed most of trifluoracetic acid, adds entry 100ml, filters, and water concentrates the back and merges with filter residue with ethyl acetate extraction 2 times, and filter residue is suspended in the saturated sodium bicarbonate solution, stirring reaction 30 hours, reaction end.Filter, filter residue is through silica gel column chromatography, and petroleum ether-ethyl acetate solution gradient drip washing purifying gets panoxadiol 1.1g, and it is 96.32% that HPLC measures purity; 20 (R) protopanoxadiol 780mg, it is 97.66% that HPLC measures purity.
Embodiment 5
Get red ginseng (total saponin content 2.36%; Available from Anhui) extract 10g is dissolved in the 100ml concentrated hydrochloric acid, sealing, room temperature stirred 80 hours, the reaction end.Filter, water concentrates the back and merges with filter residue with ethyl acetate extraction 2 times, and filter residue is suspended in the saturated sodium bicarbonate solution, stirring reaction 30 hours, reaction end.Filter, filter residue is through silica gel column chromatography, and petroleum ether-ethyl acetate solution gradient drip washing purifying gets panoxadiol 220g, and it is 96.2% that HPLC measures purity; 20 (R) protopanoxadiol 108mg, it is 97.8% that HPLC measures purity).
Embodiment 6
Herb Gynostemmae Pentaphylli (wherein the diol type ginsenoside accounts for 60%, available from Hubei) extract 10g is dissolved in the 100ml concentrated hydrochloric acid, sealing, and room temperature stirred 80 hours, and reaction finishes.Filter, water concentrates the back and merges with filter residue with ethyl acetate extraction 2 times, and filter residue is suspended in the saturated sodium bicarbonate solution, stirring reaction 30 hours, reaction end.Filter, filter residue is through silica gel column chromatography, and petroleum ether-ethyl acetate solution gradient drip washing purifying gets panoxadiol 2.62g, and it is 94.22% that HPLC measures purity; 20 (R) protopanoxadiol 1.25g, it is 96.38% that HPLC measures purity).
Claims (6)
1. the preparation method of a panoxadiol and 20 (R)-protopanoxadiols; It is characterized in that with the total saponin extracts of panax species or cauline leaf or the total saponin extracts of gynostemma plant be raw material; In solvent, carry out acid hydrolytic reaction; Through column chromatographic isolation and purification, obtain panoxadiol and 20 (R)-protopanoxadiol.
2. preparation method as claimed in claim 1, the usage ratio that it is characterized in that total saponin extracts and solvent is 10-100g/L.
3. preparation method as claimed in claim 1; It is characterized in that acid that acid hydrolytic reaction uses is one or more the nitration mixture in hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetate, trifluoroacetic acid, the oxalic acid; Preferably a kind of, concentration range is 0.2-15mol/L, stirs; Temperature of reaction is 10-120 ℃, and the reaction times is 2-80 hour.
4. preparation method as claimed in claim 1, the solvent that it is characterized in that using is saturated monohydroxy alcohol, terepthaloyl moietie, Ucar 35, the 1,3 butylene glycol, 1 of water, methyl alcohol, C2-C10,4-butyleneglycol, the mixture of one or more in the USP Kosher.
5. preparation method as claimed in claim 1 is characterized in that the used weighting agent of column chromatography is a silica gel.
6. preparation method as claimed in claim 1 is characterized in that the used eluent of column chromatography purification is two or more a mixture in methyl alcohol, chloroform, sherwood oil, acetone, ETHYLE ACETATE, methylene dichloride or the hexanaphthene.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100814735A CN102731603A (en) | 2011-03-31 | 2011-03-31 | Preparation method of panaxadiol and 20(R)-protopanaxadiol |
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| CN2011100814735A CN102731603A (en) | 2011-03-31 | 2011-03-31 | Preparation method of panaxadiol and 20(R)-protopanaxadiol |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965281A (en) * | 2013-01-31 | 2014-08-06 | 上海中药创新研究中心 | Protopanaxadiol derivative, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557830A (en) * | 2004-02-13 | 2004-12-29 | 云南白药集团天然药物研究院 | Process for preparing 20(R)-ginsenoside Rh2 |
| CN101671384A (en) * | 2009-10-12 | 2010-03-17 | 玉溪市维和生物技术有限责任公司 | Method for preparing ginsenoside Rh1 |
| US7973014B2 (en) * | 2005-07-14 | 2011-07-05 | National Institute Of Pharmaceutical R&D Co., Ltd. | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
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2011
- 2011-03-31 CN CN2011100814735A patent/CN102731603A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557830A (en) * | 2004-02-13 | 2004-12-29 | 云南白药集团天然药物研究院 | Process for preparing 20(R)-ginsenoside Rh2 |
| US7973014B2 (en) * | 2005-07-14 | 2011-07-05 | National Institute Of Pharmaceutical R&D Co., Ltd. | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
| CN101671384A (en) * | 2009-10-12 | 2010-03-17 | 玉溪市维和生物技术有限责任公司 | Method for preparing ginsenoside Rh1 |
Non-Patent Citations (1)
| Title |
|---|
| 胡晗绯: "《中国优秀硕士学位论文全文数据库 医药卫生科技辑》", 15 June 2010, article "《三七地上部分总皂苷水解产物的药学研究》", pages: 12-13 - 18-20 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965281A (en) * | 2013-01-31 | 2014-08-06 | 上海中药创新研究中心 | Protopanaxadiol derivative, preparation method and application thereof |
| WO2014117700A1 (en) * | 2013-01-31 | 2014-08-07 | 上海中药创新研究中心 | Protopanoxadiol derivative, preparation method thereof and application thereof |
| JP2016508489A (en) * | 2013-01-31 | 2016-03-22 | シャンハイ イノベーティブ リサーチ センター オブ トラディショナル チャイニーズ メディスン | Protopanaxadiol derivative, production method thereof and application thereof |
| CN103965281B (en) * | 2013-01-31 | 2016-06-08 | 上海中药创新研究中心 | A kind of protopanoxadiol derivative, its preparation method and application thereof |
| US9475836B2 (en) | 2013-01-31 | 2016-10-25 | Shang Hai Innovative Research Center Of Traditional Chinese Medicine | Protopanoxadiol derivative, preparation method thereof and application thereof |
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Application publication date: 20121017 |