CN106810555A - A kind of method that utilization metallic reducing agent is prepared matrine by oxymatrine - Google Patents
A kind of method that utilization metallic reducing agent is prepared matrine by oxymatrine Download PDFInfo
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- CN106810555A CN106810555A CN201710037463.9A CN201710037463A CN106810555A CN 106810555 A CN106810555 A CN 106810555A CN 201710037463 A CN201710037463 A CN 201710037463A CN 106810555 A CN106810555 A CN 106810555A
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- oxymatrine
- matrine
- reducing agent
- metallic reducing
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
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Abstract
The present invention relates to a kind of method that utilization metallic reducing agent is prepared matrine by oxymatrine.The method is that first the oxymatrine that purity is 65% 100% is dissolved in aqueous 50% 100% intensive polar solvent, to addition metallic reducing agent and electrolyte in solution, reacted 8 hours 0.5 hour in 40 DEG C 100 DEG C, it is 1.02~1.06 to be concentrated under reduced pressure into 50 DEG C of heat and survey relative density, concentrate is extracted using the water insoluble organic solvent of polarity 2.0 4.5, extract obtains white crystal matrine through evaporation, crystallization, centrifugation, drying.Present invention process method is easy to operate, with low cost, it is easy to industrialized production., up to more than 96%, product purity is up to more than 98% for conversion recovery rate.For matrine and oxymatrine manufacturing enterprise, it is possible to achieve the flexible conversion between two major products, to adapt to market to oxymatrine and the changes in demand of matrine.
Description
Technical field
It is more particularly to a kind of to utilize metallic reducing agent by Oxymatrine the present invention relates to Natural Medicine Chemistry technical field
The method that alkali prepares matrine.
Background technology
The effects such as legume kuh-seng, Sophora alopecuroide and subprostrate sophora all have clearing heat and detoxicating, wind dispelling insecticide, reducing pharyngeal swelling, thing
Matter basic research found in these plants containing western class D alkaloid in different degrees of quinoline promise, such as matrine, oxymatrine,
Sophoridine, sophocarpine etc..Wherein, the content highest of oxymatrine.
Oxymatrine, also known as kushenin, molecular formula are C15H24N2O2, molecular weight is 264.36.White needle form is prismatic
Crystal or white crystalline powder, odorless, bitter.207 DEG C -208 DEG C of fusing point, soluble in water, methyl alcohol, ethanol, chloroform, benzene are difficult
It is dissolved in ether.Pharmacodynamic study shows that oxymatrine has diuresis, resists B-mode and HCV, immunological regulation etc. to make
With additionally, inhibited to the vascular endothelial cell proliferation of lung cancer, stomach cancer cell induction.It is with oxymatrine at present
The medicine of raw material mainly has Sophora flavescems injection and Oxymatrine Capsule etc..
Matrine molecular formula is C15H24N2O, molecular weight is 248.37.White needles or prism crystal, odorless, bitter.It is existing
Show for pharmacological research, there is matrine antibacterial, antiviral, anti parasitic, anti-arrhythmia and anticancer etc. to act on, and clinic is conventional
In treatment bacillary dysentery and enteritis.The medicine with matrine as raw material mainly has matrine bolt etc. at present.
Matrine has medical value very high.At present, extracted from legume kuh-seng, Sophora alopecuroide and subprostrate sophora and separated
The patented technology of matrine is mainly for the preparation of oxymatrine and matrine.Patent document CN102617575A discloses one kind
Matrine is converted into the method for oxymatrine, but there are no the method that matrine is prepared by oxymatrine.
The content of the invention
It is an object of the invention to provide a kind of method that matrine is prepared by oxymatrine, for production matrine and oxygen
For changing the enterprise of matrine, it is possible to achieve the flexible conversion between two major products, adapting to market to oxymatrine and
The changes in demand of matrine, realizes maximizing the benefits.
In order to achieve the above object, the present invention is achieved through the following technical solutions：
A kind of method that utilization metallic reducing agent is prepared matrine by oxymatrine, it is characterised in that comprise the following steps：
A. oxymatrine is dissolved in the intensive polar solvent of aqueous 50%-100%；
B. to metallic reducing agent and electrolyte is added in solution, reacted -8 hours 0.5 hour in 40 DEG C -100 DEG C；
C. it is 1.02~1.06 to be concentrated under reduced pressure into 50 DEG C of heat and survey relative density；
D. concentrate is extracted using the water insoluble organic solvent of polarity 2.0-4.5；
E. extract obtains white crystal matrine through evaporation, crystallization, centrifugation, drying.
Raw material oxymatrine purity described in step a is 65%-100%.This is a significant advantage of the invention, is used
The inventive method, even if using the oxymatrine raw material compared with low-purity, it is also possible to obtain the kuh-seng that purity reaches more than 98.0%
Alkali product.
The intensive polar solvent of aqueous 50%-100% described in step a be water, or water and methyl alcohol, ethanol in any one or
Two kinds of mixed solution, consumption is 30 times -100 times of oxymatrine.Wherein adding a certain amount of methyl alcohol, ethanol can reach
Good solubilization, is conducive to oxymatrine raw material, obtains the quick dissolving of the relatively low oxymatrine raw material of purity.
The addition of metallic reducing agent described in step b is 0.5- with the mol ratio of oxymatrine addition in step a
5:1, it is preferred that reaction temperature is 60 DEG C -80 DEG C, the reaction time is -4 hours 2 hours.
Metallic reducing agent described in step b be alkali metal, alkaline-earth metal, aluminium, tin, iron, and these metals alloy and
Any one or more in its esters.
The alloy of the metal is any one or more in sodium amalgam, zinc amalgam, aluminium amalgam or magnesium amalgam, the salt
Class is any one or more in sulfate, hydrochloride or the nitrate of these metals.
Electrolyte described in step b is any one or more in inorganic acid, inorganic acid salt, acylate, addition
It is 0.1-1 with the mol ratio of oxymatrine addition in step a:1.Preferably, the inorganic acid is hydrochloric acid；Inorganic acid salt is
Any one or more in ammonium salt, molysite, sodium salt, calcium salt, barium salt, the sylvite of inorganic acid；Acylate is the sodium of organic acid
Any one or more in salt, sylvite, ammonium salt.
Step b reaction principle equations are as follows：
。
It is that 1.02~1.06 main purpose has two 50 DEG C of heat to be concentrated under reduced pressure into described in step c and surveys relative density, its
One is that appropriateness reduces the extracting operation that liquor capacity is beneficial to next step；The second is organic solvent is removed as far as possible, to ensure extraction
Take effect, yield and resulting matrine product purity.
The water insoluble organic solvent of polarity 2.0-4.5 described in step d is chloroform, dichloromethane, benzene, first
Any one or more in benzene, dimethylbenzene.Optimal effect of extracting can be obtained using these organic solvents
The purity of white crystal matrine described in step e is more than 98.0%.
Compared with prior art, the present invention has advantages below.
1. product purity is high：Products therefrom is detected using high performance liquid chromatography area normalization method, is calculated with dry product,
Matrine purity is up to more than 98%.
2. high conversion rate：The method provided using the present invention, can make oxymatrine Quantitative yield for matrine, turn
Change recovery rate to be calculated with molal quantity, up to more than 96%.
3. preparation process is simple, with low cost, it is adaptable to industrialized production.
4., for the enterprise of production oxymatrine, the method provided using the present invention can be easily achieved by aoxidizing
Matrine to matrine conversion, to adapt to market to oxymatrine and the changes in demand of matrine.
Brief description of the drawings
Fig. 1 is matrine, the high performance liquid chromatography chromatogram of oxymatrine reference substance（HPLC）Figure（Fig. 1 a）And by implementing
The high performance liquid chromatography chromatogram of the matrine sample that example 3 is obtained（HPLC）Figure（Fig. 1 b）, retention time is 10.5min's or so
The chromatographic peak of matrine, retention time is the chromatographic peak of oxymatrine 20.6min's or so, it was demonstrated that obtained by embodiment 3
Matrine sample purity；Fig. 2 is the matrine sample obtained by embodiment 31H-NMR is composed, and Fig. 3 is to be obtained by embodiment 3
The matrine sample for arriving13C-NMR is composed, it was demonstrated that product is matrine.
Specific embodiment
Technical scheme is described further with reference to specific embodiment.
Embodiment 1
Oxymatrine sterling 100g is soluble in water, it is transferred in reactor, addition 40g stannous chloride, 20g ammonium sulfate, in
After being reacted 4 hours at 50 DEG C, stop reaction, it is 1.03 to be concentrated under reduced pressure into proportion, is extracted with toluene；Extract is recovered under reduced pressure first
Benzene completely, adds acetone hot melt, crystallisation by cooling, is centrifugally separating to obtain matrine fine work 91.5g, and efficient liquid phase normalization method is measured
Purity is 99.5%, and the conversion recovery rate that oxymatrine is converted into matrine is calculated as 96.9% with molal quantity.
Embodiment 2
By oxymatrine crude product（Containing oxymatrine 75%）100g is dissolved in 50% ethanol, is transferred in reactor, adds 35g
Magnesium metal, 20g sodium acetates after being reacted 6 hours at 80 DEG C, stop reaction, and it is 1.03 to be concentrated under reduced pressure into proportion, is extracted with dimethylbenzene
Take；Extract is recovered under reduced pressure dimethylbenzene completely, acetone hot melt, crystallisation by cooling is added, matrine fine work is centrifugally separating to obtain
72.3g, it is 98.3% that efficient liquid phase normalization method measures purity, and oxymatrine is converted into the conversion recovery rate of matrine to rub
You are calculated as 100.9% by number.
Embodiment 3
By oxymatrine crude product（Containing oxymatrine 65%）1600g is soluble in water, is transferred in reactor, adds 250g gold
Category iron, 500g sodium chloride after being reacted 8 hours at 60 DEG C, stops reaction, and it is 1.03 to be concentrated under reduced pressure into proportion, is extracted with toluene；
Extract is recovered under reduced pressure toluene completely, acetone hot melt, crystallisation by cooling is added, matrine fine work 992.5g is centrifugally separating to obtain,
It is 99.0% that efficient liquid phase normalization method measures purity, and oxymatrine is converted into the conversion recovery rate of matrine in terms of molal quantity
Calculate is 100.6%.
High performance liquid chromatography is carried out to products obtained therefrom（HPLC）Analyze, HPLC chromatogram condition is：With Octadecylsilane bonded phase
Silica gel is fixing phase, the phosphoric acid solution of methyl alcohol -0.2%（10:90, V/V）It is mobile phase, flow velocity is 1mL/min, and Detection wavelength is
205nm, column temperature is 25-50 DEG C.
Fig. 1 is the high performance liquid chromatography of matrine, oxymatrine reference substance and the matrine sample obtained by embodiment 3
（HPLC）Figure.Wherein, Fig. 1 a are matrine, the high-efficient liquid phase chromatogram of oxymatrine reference substance, and Fig. 1 b are to be obtained by embodiment 3
The high-efficient liquid phase chromatogram of the matrine sample for arriving.Retention time is the chromatographic peak of matrine 10.5min's or so, during reservation
Between in 20.6min or so be the chromatographic peak of oxymatrine.
Through the matrine sample to being obtained by embodiment 3, high performance liquid chromatography normalization method is used（Corresponding diagram 1b）Carry out pure
Degree is determined, and concrete outcome is shown in Table 1.
The high performance liquid chromatography normalization method result of table 1, matrine sample
From table 1, the purity for measuring matrine is 99.27%.
Fig. 2 and Fig. 3 are the nuclear magnetic resonance map of the matrine sample obtained by embodiment 3, it was demonstrated that product is matrine.Its
In, Fig. 2 is1H-NMR collection of illustrative plates（CDCl3-d, 400MHz）, Fig. 3 is13C-NMR collection of illustrative plates（CDCl3-d, 100MHz）.Concrete signal is returned
Category is as follows：
。
1H NMR（CDCl3-d, 400MHz）：4.40（Dd, 1H,J=12,4Hz, H-17e）, 3.82（Dt, 1H,J=8,8Hz,
H-11）, 3.05（T, 1H,J=12Hz, H-17a）, 2.81（M, 2H, H-2e, H-10e）, 2.43（Dt, 1H,J=4,16Hz, H-
14e）, 2.27（Ddd, 1H,J=4,8Hz, H-14a）, 2.09（M, 2H, H-4e, H-7）, 1.98（M, 3H, H-2a, H-10a, H-
8e）, 1.66（M, 1H, H-5）, 1.58（M, 6H, H-9e, H-6, H-8a, H-12, H-13e）, 1.43（M, 5H, H-3, H-4a, H-
9a, H-13a）.
13C NMR（CDCl3-d, 100MHz）： 57.28（C-2）, 20.84（C-3）, 27.23（C-4）, 35.37（C-5）,
43.27（C-6）, 63.83（C-7）, 26.52（C-8）, 21.25（C-9）, 57.36（C-10）, 53.25（C-11）, 27.81（C-
12）, 19.07（C-13）, 32.93（C-14）, 169.48（C-15）, 41.48（C-17）.
Above-described embodiment is only the present invention preferably implementation method, and embodiments of the present invention are not by above-described embodiment
Limitation, it is noted that for those skilled in the art, do not departing from the premise of the technology of the present invention principle
Under, a lot of other modification or optimal enforcement modes are can be designed that, these modifications or optimal enforcement mode will fall in the application
Within scope of disclosure.
Claims (10)
1. a kind of method that utilization metallic reducing agent is prepared matrine by oxymatrine, it is characterised in that comprise the following steps：
A. oxymatrine is dissolved in the intensive polar solvent of aqueous 50%-100%；
B. to metallic reducing agent and electrolyte is added in solution, reacted -8 hours 0.5 hour in 40 DEG C -100 DEG C；
C. it is 1.02~1.06 to be concentrated under reduced pressure into 50 DEG C of heat and survey relative density；
D. concentrate is extracted using the water insoluble organic solvent of polarity 2.0-4.5；
E. extract obtains white crystal matrine through evaporation, crystallization, centrifugation, drying.
2. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that oxymatrine purity described in step a is 65%-100%.
3. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that the intensive polar solvent of aqueous 50%-100% described in step a is any one in water, or water and methyl alcohol, ethanol or two
The mixed solution planted, consumption is 30 times -100 times of oxymatrine.
4. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that the addition of metallic reducing agent described in step b is 0.5-5 with the mol ratio of oxymatrine addition in step a:1,
Reaction temperature is 60 DEG C -80 DEG C, and the reaction time is -4 hours 2 hours.
5. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
Be, metallic reducing agent described in step b be alkali metal, alkaline-earth metal, aluminium, tin, iron, and these metals alloy and its salt
Any one or more in class.
6. the method that a kind of utilization metallic reducing agent as claimed in claim 5 is prepared matrine by oxymatrine, its feature
It is that the alloy of the metal is any one or more in sodium amalgam, zinc amalgam, aluminium amalgam or magnesium amalgam, the salt is
Any one or more in the sulfate of these metals, hydrochloride or nitrate.
7. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that electrolyte described in step b is any one or more in inorganic acid, inorganic acid salt, acylate, addition and step
The mol ratio of oxymatrine addition is 0.1-1 in rapid a:1.
8. the method that a kind of utilization metallic reducing agent as claimed in claim 7 is prepared matrine by oxymatrine, its feature
It is that the inorganic acid is hydrochloric acid；Inorganic acid salt for inorganic acid ammonium salt, molysite, sodium salt, calcium salt, barium salt, sylvite in it is any
One or more；Acylate is any one or more in sodium salt, sylvite, the ammonium salt of organic acid.
9. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that the water insoluble organic solvent of polarity 2.0-4.5 described in step d is chloroform, dichloromethane, benzene, toluene, two
Any one or more in toluene.
10. the method that a kind of utilization metallic reducing agent as claimed in claim 1 is prepared matrine by oxymatrine, its feature
It is that the purity of matrine described in step e is more than 98.0%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107607665A (en) * | 2017-09-29 | 2018-01-19 | 贵州师范大学 | One seedling medicine subprostrate sophora and its Chinese medicine preparation method of quality control |
| CN112047946A (en) * | 2020-09-08 | 2020-12-08 | 北方民族大学 | A method for preparing matrine from oxymatrine by transfer hydrogenation |
| CN114591329A (en) * | 2022-03-03 | 2022-06-07 | 北京岳达生物科技有限公司 | Mutual transformation method of sophora flavescens effective components |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1793142A (en) * | 2005-12-27 | 2006-06-28 | 中国科学院山西煤炭化学研究所 | Process for producing high purity matrine oxide by kuh-seng |
| CN104498558A (en) * | 2015-01-15 | 2015-04-08 | 遵义医学院 | Method for preparing sophoridine using microorganisms |
-
2017
- 2017-01-19 CN CN201710037463.9A patent/CN106810555B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1793142A (en) * | 2005-12-27 | 2006-06-28 | 中国科学院山西煤炭化学研究所 | Process for producing high purity matrine oxide by kuh-seng |
| CN104498558A (en) * | 2015-01-15 | 2015-04-08 | 遵义医学院 | Method for preparing sophoridine using microorganisms |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107607665A (en) * | 2017-09-29 | 2018-01-19 | 贵州师范大学 | One seedling medicine subprostrate sophora and its Chinese medicine preparation method of quality control |
| CN112047946A (en) * | 2020-09-08 | 2020-12-08 | 北方民族大学 | A method for preparing matrine from oxymatrine by transfer hydrogenation |
| CN114591329A (en) * | 2022-03-03 | 2022-06-07 | 北京岳达生物科技有限公司 | Mutual transformation method of sophora flavescens effective components |
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