CN107286218A - A kind of preparation method of new oleanane-type triterpene saponin derivative - Google Patents
A kind of preparation method of new oleanane-type triterpene saponin derivative Download PDFInfo
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- CN107286218A CN107286218A CN201710404736.9A CN201710404736A CN107286218A CN 107286218 A CN107286218 A CN 107286218A CN 201710404736 A CN201710404736 A CN 201710404736A CN 107286218 A CN107286218 A CN 107286218A
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- FLEYVGBKDLLNQW-ILDUYXDCSA-N CCCC(CC(C)(C)C(C)[C@@H](N)S)OC Chemical compound CCCC(CC(C)(C)C(C)[C@@H](N)S)OC FLEYVGBKDLLNQW-ILDUYXDCSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/256—Polyterpene radicals
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Abstract
The invention discloses a kind of preparation method of new oleanane-type triterpene saponin derivative.The preparation method includes：（1）Glycyrrhizic acid is added in ionic liquid, proportionally fully dissolving is prepared into radix glycyrrhizae acid dissoluting liquid；（2）The concentrated sulfuric acid is added into lysate in proportion, after reaction terminates, regulation pH value separates aqueous from system；（3）By concentration, organic solvent crystallization obtains the oleanane-type triterpene saponin derivative.Reaction condition of the present invention is gentle, high income, can be recycled, and is adapted to industrialization and prepares.
Description
Technical field
The present invention relates to chemical synthesis, more particularly to a kind of preparation side of new oleanane-type triterpene saponin derivative
Method.
Background technology
Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide is a kind of new oleanane-type triterpene saponin derivative, its structure such as following formula institute
Show：
Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide
Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide (GAMG) is the product that glycyrrhizic acid (GL) loses outer end glucuronic acid base through hydrolysis.
GAMG have and the same anti-inflammatory of glycyrrhizic acid, antiviral, antitumor, Antiulcer activity, antiallergy, liver protection, reducing blood lipid and
Kobadrin and the effect of wetting one's whistle etc..Its sugariness is 5 times of GL, more than 1000 times of sucrose.In addition, GAMG has dissolubility good, just
In internal transport and the low characteristic of toxicity, it is set to be had broad application prospects on medicine and food industry.
The existing preparation method of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide has microbe transformation method, ionic liquid system acid-hydrolysis method.
Wherein microbe transformation method, although safe, it is environmentally friendly, but its severe reaction conditions, step are more, cost is high, week
Phase is long, is not suitable for industrialized production, need further research.Therefore convenience, an economic, practical chemical synthesis are found
Route is significant to prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide.
Ionic liquid (ionic liquids) refer to room temperature or close at room temperature present liquid, completely by negative and positive from
The liquid that son is constituted, also referred to as (fusing point is general for low temperature molten salt<100 ℃).Ionic liquid as ionic compound, its
The relatively low main cause of fusing point is because the asymmetry of some substituents in its structure prevents ion from being regularly piled into crystal
It is caused.It is typically made up of organic cation and inorganic anion.Ionic liquid is based on its unique characteristic, as many anti-
Catalyst, the reaction medium answered.And the effect achieved, catalytic activity is improved, reaction selectivity is improved, production is simplified
The separation process of thing, it is possible to achieve catalytic activity is high, stability is good, product can be easily separated, environment-friendly green catalysis process,
The problem of traditional handicraft is present can be overcome.Designability based on ionic liquid, will according to specific catalystic converter system feature
Ionic liquid is designed as having acid or alkalescence, or the characteristics such as its solubility, fusing point, stability are adjusted.
Acidic ionic liquid body technique constantly improves in recent years, and both small toxicity, designability with ionic liquid etc. were excellent for it
Point, have concurrently again not volatile solid acid, low corrosion, easily separated recovery and liquid acid good fluidity, acid strength be evenly distributed etc. it is excellent
Gesture, as unconventional " green " liquid acid of one kind, causes the extensive concern of people.Based on above-mentioned single glucuronic acid radix glycyrrhizae
The present Research of the preparation method of hypo acid and the advantage of acidic ion liquid, the present invention are proposed in SO42- type acidic ionic liquids
In body, realize that radix glycyrrhizae acid hydrolytic reaction generates the new method of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide.This method protrude characteristic be from
After sub- liquid is recycled five times, catalytic activity is not reduced, and yield is 90%~95%.The reaction dissolvent can realize stable urge
Change oxidation, reduce reaction condition, and can recycle, greatly reduce the pollution of environment, considerably reduce production cost,
With very big Industry Development Prospect.Document and patent report ionic liquid acidification hydrolization there is no to form single glucuronic acid at present
The report of enoxolone.
The content of the invention
Goal of the invention：The present invention will solve the severe reaction conditions that current technology is present, and step is more, and cost is high, and the cycle is long
The problems such as there is provided a kind of preparation method of new oleanane-type triterpene saponin derivative, this method relatively economical, operation side
Just, initiation material it is cheap and easy to get, can industrializing implementation.
Technical scheme：A kind of preparation method of new oleanane-type triterpene saponin derivative, including：
（1）Glycyrrhizic acid is placed in reactor, ionic liquid is added, stirring and dissolving obtains lysate；
（2）Catalyst is added in lysate, reacted, reaction terminates regulation pH value, and lower floor's aqueous is separated to obtain from system；
（3）Aqueous is concentrated to give solid, organic solvent crystallization is added, recrystallization obtains oleanane-type triterpene saponin derivative.
The chemical equation of preparation method of the present invention：
In above-mentioned steps, described glycyrrhizic acid, ionic liquid, the mass ratio of catalyst are 1:5~12:0.3~0.5.Preferably
1:8:0.4, the complete reaction of glycyrrhizic acid is can fully ensure that, if ionic liquid glycyrrhizic acid indissoluble solution very little, then causes wave too much
Take, too little catalyst is then not sufficiently reacted, then accessory substance is more too much.
Above-mentioned steps（1）In, described ionic liquid cation for the methylimidazole of 1- ethyls -3 [Emim]+；Ionic liquid it is cloudy from
Son is one kind in BF4-, PF6-, AlCl4-, NO2-, ClO2-, SbF6-, (CF3SO2) 3C-, CF3COO-.Anion is preferred
For BF4-.
Above-mentioned steps（2）In, described catalyst is the concentrated sulfuric acid, and it in reaction temperature is 10 ~ 50 that described reaction condition, which is,
1 ~ 6 h is reacted at DEG C.The too high side reaction thing that easily causes of reaction temperature increases, too low to cause reaction slow, it is impossible to fully reaction.It is excellent
The reaction temperature of choosing is 30 DEG C, and the reaction time preferably is 3h.
Above-mentioned steps（2）In, described regulation pH value is heightened or turned down and all cause separating difficulty big, during separation to 8 ~ 9
Between it is long the problem of.It is preferred that pH value be 8.
Above-mentioned steps（3）In, described organic solvent is one kind in methanol, ethanol, propane diols, glacial acetic acid, according to matter
Amount is than being 1:6 ~ 10, organic solvent is more to cause derivative yield low.Preferably mass ratio is 1:8 methanol.
Compared with prior art, effective effect of the invention includes：
The present invention uses chemical synthesising technology there is provided a kind of preparation method of new oleanane-type triterpene saponin derivative,
It is raw material glycyrrhizic acid abundance in this method, readily available；Cheap, reaction dissolvent is recycled, environmental protection；Reaction condition
Gently, high income, is adapted to industrialized production, it is easy to promote, with very strong practicality.
Embodiment
The present invention is described in detail in conjunction with embodiment detailed description technical scheme with reference to specific embodiment.
All embodiments are all operated in strict accordance with the operating procedure of above-mentioned preparation method, to simplify style of writing, with
Each embodiment only enumerates the technical data of key down.
Embodiment 1
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ BF4 ionic liquid 80g, stirring and dissolving；Add the concentrated sulfuric acid
3g, at a temperature of 30 DEG C, raw material obtains single glucuronic acid in 3 hours under ionic liquid system through sulphuric acid catalysis hydrolysis
Enoxolone, reaction solution is adjusted after pH to 8, stratification with ammoniacal liquor, ionic liquid and aqueous phase in separation reaction solution, lower floor's water
Phase vacuum rotary steam obtains solid, and revolving gained solid is dissolved in into 80g methanol, cooling recrystallize the mono- glucuronic acids of 7.07g are sweet
Careless hypo acid sterling, yield is 90%.
Embodiment 2
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ PF6 ionic liquid 60g, stirring and dissolving；Add the concentrated sulfuric acid
4g, at a temperature of 40 DEG C, raw material obtains single glucuronic acid in 2 hours under ionic liquid system through sulphuric acid catalysis hydrolysis
Enoxolone, reaction solution is adjusted after pH to 8, stratification with ammoniacal liquor, ionic liquid and aqueous phase in separation reaction solution, lower floor's water
Phase vacuum rotary steam obtains solid, and revolving gained solid is dissolved in into 80g ethanol, cooling recrystallize the mono- glucuronic acids of 7.30g are sweet
Careless hypo acid sterling, yield is 93%.
Embodiment 3
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ ClO2 ionic liquid 100g, stirring and dissolving；Add dense sulphur
Sour 4g, at a temperature of 45 DEG C, raw material obtains single grape alditol for 2 hours under ionic liquid system through sulphuric acid catalysis hydrolysis
Sour enoxolone, reaction solution is adjusted after pH to 9, stratification with ammoniacal liquor, ionic liquid and aqueous phase in separation reaction solution, lower floor
Aqueous phase vacuum rotary steam obtains solid, revolving gained solid is dissolved in into 70g glacial acetic acid, cooling recrystallizes to obtain the mono- grape alditols of 7.12g
Sour enoxolone sterling, yield is 90.7%.
Embodiment 4
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ BF4 ionic liquid 50g, stirring and dissolving；Add the concentrated sulfuric acid
5g, at a temperature of 50 DEG C, raw material obtains single glucuronic acid in 1 hour under ionic liquid system through sulphuric acid catalysis hydrolysis
Enoxolone, reaction solution is adjusted after pH to 8, stratification with ammoniacal liquor, ionic liquid and aqueous phase in separation reaction solution, lower floor's water
Phase vacuum rotary steam obtains solid, revolving gained solid is dissolved in into 60g propane diols, cooling recrystallizes to obtain the mono- glucuronic acids of 7.22g
Enoxolone sterling, yield is 92.0%.
Embodiment 5
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ (CF3SO2) 3C ionic liquid 120g, stirring and dissolving；Plus
Enter concentrated sulfuric acid 5g, at a temperature of 10 DEG C, raw material obtains single Portugal in 6 hours under ionic liquid system through sulphuric acid catalysis hydrolysis
Grape uronic acid enoxolone, reaction solution is adjusted after pH to 8, stratification with ammoniacal liquor, ionic liquid and water in separation reaction solution
Phase, lower floor's aqueous phase vacuum rotary steam obtains solid, revolving gained solid is dissolved in into 100g methanol, cooling recrystallizes to obtain the mono- Portugals of 7.38g
Grape uronic acid enoxolone sterling, yield is 94.0%.
Embodiment 6
Weigh glycyrrhizic acid 10g to be placed in reactor, add ［ Emim ］ NO2 ionic liquid 100g, stirring and dissolving；Add the concentrated sulfuric acid
4g, at a temperature of 40 DEG C, raw material obtains single glucuronic acid in 3 hours under ionic liquid system through sulphuric acid catalysis hydrolysis
Enoxolone, reaction solution is adjusted after pH to 9, stratification with ammoniacal liquor, ionic liquid and aqueous phase in separation reaction solution, lower floor's water
Phase vacuum rotary steam obtains solid, and revolving gained solid is dissolved in into 80g ethanol, cooling recrystallize the mono- glucuronic acids of 7.33g are sweet
Careless hypo acid sterling, yield is 93.3%.
Claims (6)
1. a kind of preparation method of new oleanane-type triterpene saponin derivative, it is characterised in that including：
（1）Glycyrrhizic acid is placed in reactor, ionic liquid is added, stirring and dissolving obtains lysate；
（2）Catalyst is added in lysate, reacted, reaction terminates regulation pH value, and lower floor's aqueous is separated to obtain from system；
（3）Aqueous is concentrated to give solid, organic solvent crystallization is added, obtains oleanane-type triterpene saponin derivative.
2. preparation method according to claim 1, it is characterised in that described glycyrrhizic acid, ionic liquid, the matter of catalyst
Amount is than being 1:5~12:0.3~0.5.
3. preparation method according to claim 1, it is characterised in that step（1）In, described ionic liquid cation is 1-
The methylimidazole of ethyl -3 [Emim]+；Ion solution anion be BF4-, PF6-, AlCl4-, NO2-, ClO2-, SbF6-,
(CF3SO2) one kind in 3C-, CF3COO-.
4. preparation method according to claim 1, it is characterised in that step（2）In, described catalyst is the concentrated sulfuric acid,
Reaction temperature is 10 ~ 50 DEG C, and the reaction time is 1 ~ 6 h.
5. preparation method according to claim 1, it is characterised in that step（2）In, described regulation pH value to 8 ~ 9.
6. preparation method according to claim 1, it is characterised in that step（3）In, described organic solvent is methanol,
One kind in ethanol, propane diols, glacial acetic acid.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710404736.9A CN107286218B (en) | 2017-06-01 | 2017-06-01 | A kind of preparation method of new oleanane-type triterpene saponin derivative |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108576764A (en) * | 2018-03-20 | 2018-09-28 | 亿利耐雀生物科技有限公司 | A kind of Antialcoholic liver-protecting compound sweetener and preparation method thereof |
| CN108948105A (en) * | 2018-07-13 | 2018-12-07 | 沈阳药科大学 | A kind of chemical synthesis process of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide |
| CN114246875A (en) * | 2021-12-15 | 2022-03-29 | 亿利耐雀生物科技有限公司 | Anti-inflammatory and freckle-removing compound nicotinamide composition and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588849A (en) * | 2012-08-14 | 2014-02-19 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid |
| CN103788167A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid monoglucuronide (GAMG) |
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2017
- 2017-06-01 CN CN201710404736.9A patent/CN107286218B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588849A (en) * | 2012-08-14 | 2014-02-19 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid |
| CN103788167A (en) * | 2012-10-31 | 2014-05-14 | 江苏汉邦科技有限公司 | Preparation method for glycyrrhetinic acid monoglucuronide (GAMG) |
Non-Patent Citations (2)
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| 徐静: "甘草次酸及乙酰甘草次酸的制备和纯化研究", 《兰州理工大学硕士学位论文》 * |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108576764A (en) * | 2018-03-20 | 2018-09-28 | 亿利耐雀生物科技有限公司 | A kind of Antialcoholic liver-protecting compound sweetener and preparation method thereof |
| CN108948105A (en) * | 2018-07-13 | 2018-12-07 | 沈阳药科大学 | A kind of chemical synthesis process of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide |
| CN108948105B (en) * | 2018-07-13 | 2021-04-02 | 沈阳药科大学 | Chemical synthesis method of glycyrrhetinic acid monoglucuronide |
| CN114246875A (en) * | 2021-12-15 | 2022-03-29 | 亿利耐雀生物科技有限公司 | Anti-inflammatory and freckle-removing compound nicotinamide composition and application thereof |
| CN114246875B (en) * | 2021-12-15 | 2024-05-10 | 亿利耐雀生物科技有限公司 | Anti-inflammatory and freckle-removing compound nicotinamide composition and application thereof |
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