CN107286218B - 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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- CN107286218B CN107286218B CN201710404736.9A CN201710404736A CN107286218B CN 107286218 B CN107286218 B CN 107286218B CN 201710404736 A CN201710404736 A CN 201710404736A CN 107286218 B CN107286218 B CN 107286218B
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- 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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- 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 methods of new oleanane-type triterpene saponin derivative.The preparation method includes: that (1) glycyrrhizic acid is added in ionic liquid, and proportionally sufficiently dissolution is prepared into Radix Glycyrrhizae acid dissoluting liquid；(2) concentrated sulfuric acid is added into lysate in proportion, after reaction, adjusts pH value and separate aqueous from system；(3) by concentration, organic solvent crystallization obtains the oleanane-type triterpene saponin derivative.Reaction condition of the present invention is mild, high income, can be recycled, and is suitble to industrialization preparation.
Description
Technical field
The present invention relates to chemical syntheses, more particularly to a kind of preparation side of new oleanane-type triterpene saponin derivative
Method.
Background technique
Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide is a kind of new oleanane-type triterpene saponin derivative, 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 production that glycyrrhizic acid (GL) loses outer end glucuronic acid base through hydrolyzing
Object.GAMG has anti-inflammatory same with glycyrrhizic acid, antiviral and antitumor, Antiulcer activity, antiallergy, liver protection, reducing blood lipid
The effects of with kobadrin and throat soothing.Its sugariness is 5 times of GL, more than 1000 times of sucrose.In addition, GAMG have dissolubility it is good,
Convenient for transporting in vivo and the characteristics such as toxicity is low, it is made to have 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, environmentally friendly although highly-safe, its severe reaction conditions, step are more, at high cost, all
Phase is long, is not suitable for industrialized production, needs to be further studied.Therefore a convenience, economic, practical chemical synthesis are found
Route is of great significance 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 yin-yang from
Liquid composed by son, also referred to as low temperature molten salt (fusing point general < 100 DEG C).Ionic liquid is melted as ionic compound
The main reason for point is lower is because the asymmetry of substituent groups certain in its structure prevents ion from being regularly piled into crystal institute
It causes.It is generally made of organic cation and inorganic anion.Ionic liquid is based on its unique characteristic, has been used as many reactions
Catalyst, reaction medium.And the effect achieved, catalytic activity is improved, reaction selectivity is improved, simplifies product
Separation process, the green catalysis process that catalytic activity is high, stability is good, product can be easily separated, environmental-friendly may be implemented, can
To overcome the problems, such as that traditional handicraft exists.Designability based on ionic liquid, will be from according to specific catalystic converter system feature
Sub- liquid is designed as having acid or alkalinity, or is adjusted to characteristics such as its solubility, fusing point, stability.
Acidic ionic liquid body technique is constantly progressive in recent years, has both had small toxicity, designability of ionic liquid etc. excellent
Point, but have not volatile solid acid concurrently, low corrosion, easily separated recycling and liquid acid good fluidity, acid strength be evenly distributed etc. it is excellent
Gesture causes the extensive concern of people as a kind of unconventional " green " liquid acid.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 ion liquid
In, realize that Radix Glycyrrhizae acid hydrolytic reaction generates the new method of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide.This method characteristic outstanding is ion
After liquid is recycled five times, catalytic activity is not reduced, and yield is 90%~95%.Stable catalysis may be implemented in the reaction dissolvent
Oxidation reduces reaction condition, and can be recycled, and greatly reduces the pollution of environment, considerably reduces production cost, has
There is very big Industry Development Prospect.Document and patent report ionic liquid acidification hydrolization there is no to form single glucuronic acid at present sweet
The report of careless hypo acid.
Summary of the invention
Goal of the invention: the present invention will solve severe reaction conditions existing for current technology, and step is more, at high cost, and the period is long
The problems such as, a kind of preparation method of new oleanane-type triterpene saponin derivative, this method relatively economical, operation side are provided
Just, starting material it is cheap and easy to get, can industrializing implementation.
A kind of technical solution: preparation method of new oleanane-type triterpene saponin derivative, comprising:
(1) glycyrrhizic acid is placed in reactor, ionic liquid is added, stirring and dissolving obtains lysate；
(2) catalyst is added in lysate, is reacted, reaction terminates to adjust pH value, and lower layer is separated to obtain from system
Aqueous；
(3) aqueous is concentrated to give solid, organic solvent crystallization is added, it is derivative to obtain oleanane-type triterpene saponin for recrystallization
Object.
The chemical equation of preparation method of the present invention:
Glycyrrhizic acid Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide
In above-mentioned steps, the glycyrrhizic acid, ionic liquid, catalyst mass ratio be 1:5~12:0.3~0.5.It is excellent
Be selected as 1:8:0.4, can fully ensure that the complete reaction of glycyrrhizic acid, if the very little glycyrrhizic acid indissoluble solution of ionic liquid, too much if cause
Waste, too little catalyst are then not sufficiently reacted, and then by-product is more too much.
In above-mentioned steps (1), the ionic liquid cation be -3 methylimidazole of 1- ethyl [Emim]+；Ionic liquid yin from
Son is one of BF4-, PF6-, AlCl4-, NO2-, ClO2-, SbF6-, (CF3SO2) 3C-, CF3COO-.Anion is preferred
For BF4-.
In above-mentioned steps (2), the catalyst is the concentrated sulfuric acid, and it is 10~50 that the reaction condition, which is in reaction temperature,
1~6h is reacted at DEG C.Reaction temperature is excessively high to be easy to cause side reaction object to increase, too low to cause reaction slow, is not sufficiently reacted.It is excellent
The reaction temperature of choosing is 30 DEG C, and the preferred reaction time is 3h.
In above-mentioned steps (2), the adjusting pH value to 8~9 is turned up or is turned down and all causes separating difficulty big, separation
The problem of time length.Preferred pH value is 8.
In above-mentioned steps (3), the organic solvent is one of methanol, ethyl alcohol, propylene glycol, glacial acetic acid, according to matter
Amount is than being 1:6~10, and organic solvent, and to will 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, provides a kind of preparation side of new oleanane-type triterpene saponin derivative
Method, it is raw material glycyrrhizic acid abundance in this method, readily available；Cheap, reaction dissolvent is recyclable, environmentally protective；Reaction
Mild condition, high income are suitble to industrialized production, easy to spread, have very strong practicability.
Specific embodiment
The present invention will be described in detail combined with specific embodiments below now in conjunction with the embodiment technical solution that the present invention will be described in detail.
All embodiments are all operated in strict accordance with the operating procedure of above-mentioned preparation method, to simplify style of writing, with
Under each embodiment only enumerate crucial technical data.
Embodiment 1
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] BF4 ionic liquid 80g, stirring and dissolving；It is added dense
Sulfuric acid 3g, 30 DEG C at a temperature of, raw material obtained single glucose through sulphuric acid catalysis hydrolysis 3 hours under ionic liquid system
Aldehydic acid enoxolone, reaction solution adjusts pH to 8 with ammonium hydroxide, after stratification, separates the ionic liquid and water phase in reaction solution, under
Layer water phase vacuum rotary steam obtains solid, revolving obtained solid is dissolved in 80g methanol, cooling recrystallizes to obtain the mono- grape alditol of 7.07g
Sour enoxolone sterling, yield 90%.
Embodiment 2
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] PF6 ionic liquid 60g, stirring and dissolving；It is added dense
Sulfuric acid 4g, 40 DEG C at a temperature of, raw material obtained single glucose through sulphuric acid catalysis hydrolysis 2 hours under ionic liquid system
Aldehydic acid enoxolone, reaction solution adjusts pH to 8 with ammonium hydroxide, after stratification, separates the ionic liquid and water phase in reaction solution, under
Layer water phase vacuum rotary steam obtains solid, revolving obtained solid is dissolved in 80g ethyl alcohol, cooling recrystallizes to obtain the mono- grape alditol of 7.30g
Sour enoxolone sterling, yield 93%.
Embodiment 3
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] ClO2 ionic liquid 100g, stirring and dissolving；It is added
Concentrated sulfuric acid 4g, 45 DEG C at a temperature of, raw material obtained single grape through sulphuric acid catalysis hydrolysis 2 hours under ionic liquid system
Uronic acid enoxolone, reaction solution adjusts pH to 9 with ammonium hydroxide, after stratification, separates the ionic liquid and water phase in reaction solution,
Lower water phase vacuum rotary steam obtains solid, revolving obtained solid is dissolved in 70g glacial acetic acid, cooling recrystallizes to obtain the mono- grape of 7.12g
Uronic acid enoxolone sterling, yield 90.7%.
Embodiment 4
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] BF4 ionic liquid 50g, stirring and dissolving；It is added dense
Sulfuric acid 5g, 50 DEG C at a temperature of, raw material obtained single glucose through sulphuric acid catalysis hydrolysis 1 hour under ionic liquid system
Aldehydic acid enoxolone, reaction solution adjusts pH to 8 with ammonium hydroxide, after stratification, separates the ionic liquid and water phase in reaction solution, under
Layer water phase vacuum rotary steam obtains solid, revolving obtained solid is dissolved in 60g propylene glycol, cooling recrystallizes to obtain the mono- glucose of 7.22g
Aldehydic acid enoxolone sterling, yield 92.0%.
Embodiment 5
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] (CF3SO2) 3C ionic liquid 120g, stir molten
Solution；Concentrated sulfuric acid 5g is added, 10 DEG C at a temperature of, raw material is under ionic liquid system through sulphuric acid catalysis hydrolysis 6 hours
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide, reaction solution ammonium hydroxide adjusts pH to 8, after stratification, separates the ionic liquid in reaction solution
Body and water phase, lower water phase vacuum rotary steam obtain solid, revolving obtained solid are dissolved in 100g methanol, cooling recrystallizes
7.38g Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide sterling, yield 94.0%.
Embodiment 6
It weighs glycyrrhizic acid 10g to be placed in reactor, adds [Emim] NO2 ionic liquid 100g, stirring and dissolving；It is added dense
Sulfuric acid 4g, 40 DEG C at a temperature of, raw material obtained single glucose through sulphuric acid catalysis hydrolysis 3 hours under ionic liquid system
Aldehydic acid enoxolone, reaction solution adjusts pH to 9 with ammonium hydroxide, after stratification, separates the ionic liquid and water phase in reaction solution, under
Layer water phase vacuum rotary steam obtains solid, revolving obtained solid is dissolved in 80g ethyl alcohol, cooling recrystallizes to obtain the mono- grape alditol of 7.33g
Sour enoxolone sterling, yield 93.3%.
Claims (3)
1. a kind of preparation method of oleanane-type triterpene saponin derivative characterized by comprising
(1) glycyrrhizic acid is placed in reactor, ionic liquid is added, stirring and dissolving obtains lysate；
(2) catalyst is added in lysate, is reacted, reaction terminates to adjust pH value, and lower layer'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；
In above-mentioned steps (1), the ionic liquid cation be -3 methylimidazole of 1- ethyl [Emim]+；Ion solution anion is
One of BF4-, PF6-, AlCl4-, NO2-, ClO2-, SbF6-, (CF3SO2) 3C-, CF3COO-；
In step (2), the catalyst is the concentrated sulfuric acid, and reaction temperature is 10~50 DEG C, and the reaction time is 1~6h；
In step (3), the organic solvent is one of methanol, ethyl alcohol, propylene glycol, glacial acetic acid.
2. preparation method according to claim 1, which is characterized in that the matter of the glycyrrhizic acid, ionic liquid, catalyst
Amount is than being 1:5~12:0.3~0.5.
3. preparation method according to claim 1, which is characterized in that in step (2), the adjusting pH value to 8~9.
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| 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 |
| CN108948105B (en) * | 2018-07-13 | 2021-04-02 | 沈阳药科大学 | Chemical synthesis method of glycyrrhetinic acid monoglucuronide |
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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- 2017-06-01 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)
| Title |
|---|
| 含离子液体体系中固定化细胞转化甘草酸生成单葡萄糖醛酸基甘草次酸;陈金燕等;《生物加工过程》;20110930;第9卷(第5期);第17-21页 |
| 甘草次酸及乙酰甘草次酸的制备和纯化研究;徐静;《兰州理工大学硕士学位论文》;20110824;第26-27页 |
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