CN108440521A - A method of it producing waste liquid of saltouing using fibrauretine and prepares fibrauretine - Google Patents
A method of it producing waste liquid of saltouing using fibrauretine and prepares fibrauretine Download PDFInfo
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- CN108440521A CN108440521A CN201810534606.1A CN201810534606A CN108440521A CN 108440521 A CN108440521 A CN 108440521A CN 201810534606 A CN201810534606 A CN 201810534606A CN 108440521 A CN108440521 A CN 108440521A
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- fibrauretine
- alkaloid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
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Abstract
The method that waste liquid of saltouing prepares fibrauretine is produced using fibrauretine the invention discloses a kind of, fibrauretine production is saltoutd after waste liquid adjusts pH with alkali and is filtered by this method, filtrate passes through resin column enriched biological alkali, first with purifying water elution impurity, again alkaloid is eluted with ethanol solution, eluent concentrates the dry alkaloid mixture obtained containing jateorrhizine, Palmatine and jateorrhizine, it methylates with iodomethane after the dissolving of alkaloid mixture, resin column enriched biological alkali again, after salt acid for adjusting pH, fibrauretine crude product is made；Fibrauretine crude product is through ethyl alcohol recrystallization, filtering, dry fibrauretine；Fibrauretine is produced waste liquid recycling by the present invention, and herba fibraureae recisae cellulose content ＞ 98% obtained improves resource utilization, reduces production cost, and the method that fibrauretine is made is simple to operation, is suitable for industrialized production.
Description
Technical field
The invention belongs to chemicals preparing technical field, it is related to a kind of preparing herba fibraureae recisae using fibrauretine production waste liquid of saltouing
The method of element.
Background technology
Fibrauretine is called Palmatine Hydro-chloride, entitled 5, the 6- dihydros -2,3 of chemistry, 9,10- tetramethoxy dibenzo [a, g]
Quinolizine inner salt has the pharmacological actions such as broad-spectrum antiseptic, antivirus action, anti-inflammatory, increase phagocytic activity of leukocytes, is made
It is applied to clinic at several formulations, can be used for treating gynaecological imflammation, bacillary dysentery, enteritis, respiratory tract and urethral infection, surgical infection
And conjunctivitis etc.；Fibrauretine Hydrolysis kinetics can be obtained from the drying rattan of menispermaceous plants herba fibraureae recisae Caulis Fibraurear
It arrives, but scarcity of resources, short supply at present.
In herba fibraureae recisae in addition to containing Palmatine, also jateorrhizine, jateorrhizine, fibranine, fibraminine, fibralactone,
Sterol etc..Wherein jateorrhizine and the structure of jateorrhizine is similar with fibrauretine, and fibrauretine can be synthesized by methylation reaction.
The industrial process of fibrauretine is, by the sulfuric acid of herba fibraureae recisae coarse powder 0.3-0.5%, then saltouts, crystallizes.
Liquid of saltouing there remains outside 1/4 or so fibrauretine, also the jateorrhizine containing equivalent or so and a part of jateorrhizine, by medicine root
Alkali and jateorrhizine are converted into fibrauretine, while the fibrauretine recycled in liquid of saltouing is significantly.However, for a long time with
Come, these waste liquids are thrown aside, and the serious waste of resource is caused.
Invention content
It is saltoutd the method that waste liquid prepares fibrauretine using fibrauretine production the present invention provides a kind of, this method is by fibrauretine
Production is saltoutd after waste liquid adjusts pH with alkali and is filtered, and filtrate first uses purifying water elution impurity, then use by resin column enriched biological alkali
Ethanol solution elutes alkaloid, and eluent concentrates the dry alkaloid mixing obtained containing jateorrhizine, Palmatine and jateorrhizine
Object methylates after the dissolving of alkaloid mixture with iodomethane, again resin column enriched biological alkali, and after salt acid for adjusting pH, Huang is made
Rattan element crude product；Fibrauretine crude product is filtered through ethyl alcohol recrystallization, dry, obtains the fibrauretine of 98% or more content.
Specific technical solution of the present invention is as follows：
（1）Fibrauretine produces waste liquid alkali of saltouing and adjusts pH=9~10, filtering；
（2）By step（1）Filtrate is by resin column, and after filtrate completion of the sample, the purifying water elution with 3~4 times of column volumes is miscellaneous
Matter；
（3）With the alkaloid on ethanol solution elution resin column, is differentiated with TLC thin layers, collect alkaloid section eluent；
（4）The alkaloid mixture containing jateorrhizine, Palmatine and jateorrhizine is obtained after the concentration of alkaloid section eluent；
（5）The tetrahydrofuran of 9~11 times of its quality of alkaloid mixture is dissolved, alkaloid mixture quality is then added
The iodomethane of 1~1.5 times of alkaloid mixture quality is added dropwise in 0.1~0.2 times of 4-dimethylaminopyridine, after the completion of reaction
Isometric purified water is added in reaction solution, is adsorbed by resin column after mixing, is then rushed with the purified water of 2~3 times of column volumes
Pillar is washed, then alkaloid is eluted with the ethanol solution of volumetric concentration 80~90%, alkaloid section eluent is collected, is concentrated under reduced pressure into
Concentrate quality is made a living 3~4 times of alkaloids mixture quality, and with hydrochloric acid tune pH=2~3, cold filtration, filter residue is dried to get Huang
Rattan element crude product；
（6）In step（5）Be added in fibrauretine crude product the volumetric concentration 80~90% of 10~12 times of its quality ethanol solution and its
The activated carbon that 0.1~0.2 times of quality, after heating fibrauretine crude product dissolving, reflow treatment 20~30min filterings, filtrate stands 24
Hour, it then filters, filter residue is dried to get fibrauretine.
The sodium hydroxide that the fibrauretine produces waste liquid mass concentration 35~45% of saltouing adjusts pH value.
Resin is AB-8 or D101 resins in the resin column.
The step（3）The volumetric concentration of middle ethanol solution is 60~70%.
The advantages of the method for the present invention and technique effect：The present invention saltouts waste liquid as raw material, energy in being produced using fibrauretine
It is enough fibrauretine to be produced into jateorrhizine in waste liquid and jateorrhizine is converted into the fibrauretine with clinical medical value, change give up into
Treasured, while the fibrauretine that fibrauretine is saltoutd in waste liquid is recycled, improve the utilization rate of resource；Major impurity in fibrauretine product
It is jateorrhizine and jateorrhizine, jateorrhizine and jateorrhizine are converted into fibrauretine, therefore herba fibraureae recisae obtained by the invention
Cellulose content is up to 98% or more；The invention is with production cost is low, process engineering is simple, easy to operate, herba fibraureae recisae cellulose content obtained is high
Feature.
Specific implementation mode
With reference to embodiment, invention is further described in detail, but protection scope of the present invention be not limited to it is described
Content in the method for the present invention is unless otherwise specified all made of conventional method, unless otherwise specified using reagent, is all made of routine
The reagent or commercially available conventional reagent that method is prepared.
Embodiment 1：Fibrauretine is taken to produce the waste liquid 10L that saltouts, with sodium hydroxide tune pH=9.5 of mass concentration 40%, filtering；
For filtrate by AB-8 resin columns, flow velocity is 1 column volume/h, and after filtrate is covered, resin column is washed with the purifying of 3 times of column volumes,
Impurity is eluted, the ethanol solution of volumetric concentration 60% is then used, alkaloid, elution are eluted according to the flow velocity of 1 column volume per hour
Liquid is detected using TLC contact plates, collects alkaloid section eluent；Concentrate 20.2g is obtained after the concentration of alkaloid section eluent；Concentration
Object 202g tetrahydrofurans dissolve, and 2.02gDMAP is then added, 20.2g iodomethane is slowly added dropwise, continues to stir after being added dropwise to complete
30 minutes, isometric purified water is added in reaction solution, is adsorbed by AB-8 resin columns after mixing, then with 2 times of column volumes
Purified water rinse pillar, then elute alkaloid with the ethanol solution of volumetric concentration 80%, collect alkaloid section eluent, depressurize
It is concentrated into 61g, is adjusted to pH=2 with hydrochloric acid, cooled and filtered is dry, obtains fibrauretine crude product 16.2g；Body is added in fibrauretine crude product
The ethanol solution 194g and activated carbon 1.62g of product concentration 85%, reflow treatment 20 minutes after heating fibrauretine crude product dissolving, while hot
Filtering, being stored at room temperature 24 hours makes crystallization, filtering, and crystal is placed in drying at 70 DEG C, obtains fibrauretine 10.1g, content 98.2%.
Embodiment 2：Fibrauretine is taken to produce the waste liquid 10L that saltouts, with sodium hydroxide tune pH=9 of mass concentration 35%, filtering；Filter
For liquid by D101 resin columns, flow velocity is 2 column volume/h, after filtrate is covered, washes resin column with the purifying of 4 times of column volumes, washes
Then removing impurities matter uses the ethanol solution of volumetric concentration 70%, alkaloid, eluent are eluted according to the flow velocity of 2 column volumes per hour
It is detected using TLC contact plates, collects alkaloid section eluent；Concentrate 19.8g is obtained after the concentration of alkaloid section eluent；Concentrate
It is dissolved with 179g tetrahydrofurans, 2.97gDMAP is then added, 29g iodomethane is slowly added dropwise, continue 30 points of stirring after being added dropwise to complete
Isometric purified water is added in reaction solution, is adsorbed by D101 resin columns after mixing for clock, then pure with 3 times of column volumes
Change water and rinse pillar, then alkaloid is eluted with the ethanol solution of volumetric concentration 85%, collects alkaloid section eluent, be concentrated under reduced pressure
To 70g, pH=3 are adjusted to hydrochloric acid, cooled and filtered is dry, obtains fibrauretine crude product 15.4g；Add volumetric concentration in fibrauretine crude product
Enter 85% ethanol solution 154g and activated carbon 3g, flows back 30 minutes, filter while hot, being stored at room temperature 24 hours makes knot after heating for dissolving
Crystalline substance, filtering, crystal are placed in drying at 70 DEG C, obtain fibrauretine 9.6g, content 98.1%.
Embodiment 3：Fibrauretine is taken to produce the waste liquid 100L that saltouts, with sodium hydroxide tune pH=10 of mass concentration 45%, filtering；
Filtrate is by AB-8 resin columns, and flow velocity is 1.5 column volume/h, after filtrate is covered, with the purifying washed resin of 3.5 times of column volumes
Column elutes impurity, then uses the ethanol solution of volumetric concentration 65%, and biology is eluted according to the flow velocity of 1.5 column volumes per hour
Alkali, eluent are detected using TLC contact plates, collect alkaloid section eluent；Concentrate is obtained after the concentration of alkaloid section eluent
210g；Concentrate 2100g tetrahydrofurans dissolve, and 31gDMAP is then added, 250g iodomethane is slowly added dropwise, after being added dropwise to complete
Continue stirring 30 minutes, isometric purified water is added in reaction solution, is adsorbed by AB-8 resin columns after mixing, is then used
The purified water of 2.5 times of column volumes rinses pillar, then elutes alkaloid with the ethanol solution of volumetric concentration 90%, collects alkaloid section
Eluent is concentrated under reduced pressure into 760g, is adjusted to pH=2.5 with hydrochloric acid, cooled and filtered is dry, obtains fibrauretine crude product 170g；In Huang
The ethanol solution 1870g and activated carbon 20g of volumetric concentration 90% is added in rattan element crude product, after heating fibrauretine crude product dissolving at reflux
Reason 25 minutes, is filtered while hot, and being stored at room temperature 24 hours makes crystallization, filtering, and crystal is placed in drying at 70 DEG C, obtains fibrauretine 106g,
Content is 98.5%.
Embodiment 4：Fibrauretine is taken to produce the waste liquid 100L that saltouts, with sodium hydroxide tune pH=10 of mass concentration 40%, filtering；
For filtrate by D101 resin columns, flow velocity is 1 column volume/h, and after filtrate is covered, resin column is washed with the purifying of 3 times of column volumes,
Impurity is eluted, the ethanol solution of volumetric concentration 62% is then used, alkaloid, elution are eluted according to the flow velocity of 2 column volumes per hour
Liquid is detected using TLC contact plates, collects alkaloid section eluent；Concentrate 195g is obtained after the concentration of alkaloid section eluent；Concentration
Object 2145g tetrahydrofurans dissolve, and 19.5gDMAP is then added, 195g iodomethane is slowly added dropwise, continues to stir after being added dropwise to complete
30 minutes, isometric purified water is added in reaction solution, is adsorbed by AB-8 resin columns after mixing, then with 2 times of column volumes
Purified water rinse pillar, then elute alkaloid with the ethanol solution of volumetric concentration 85%, collect alkaloid section eluent, depressurize
It is concentrated into 780g, is adjusted to pH=2.5 with hydrochloric acid, cooled and filtered is dry, obtains fibrauretine crude product 148g；It is added in fibrauretine crude product
The ethanol solution 1776g and activated carbon 14.8g of volumetric concentration 85%, reflow treatment 20 minutes, takes advantage of after heating fibrauretine crude product dissolving
Heat filtering, being stored at room temperature 24 hours makes crystallization, filtering, and crystal is placed in drying at 70 DEG C, obtains fibrauretine 95g, content 98.8%.
Embodiment 5：Fibrauretine is taken to produce the waste liquid 500L that saltouts, with sodium hydroxide tune pH=9 of mass concentration 35%, filtering；
For filtrate by AB-8 resin columns, flow velocity is 2 column volume/h, and after filtrate is covered, resin column is washed with the purifying of 4 times of column volumes,
Impurity is eluted, the ethanol solution of volumetric concentration 66% is then used, alkaloid, elution are eluted according to the flow velocity of 2 column volumes per hour
Liquid is detected using TLC contact plates, collects alkaloid section eluent；Concentrate 1.1kg is obtained after the concentration of alkaloid section eluent；Concentration
Object 11kg tetrahydrofurans dissolve, and 220gDMAP is then added, 1.3kg iodomethane is slowly added dropwise, continues to stir after being added dropwise to complete
30 minutes, isometric purified water is added in reaction solution, is adsorbed by AB-8 resin columns after mixing, then with 2 times of column volumes
Purified water rinse pillar, then elute alkaloid with the ethanol solution of volumetric concentration 86%, collect alkaloid section eluent, depressurize
It is concentrated into 3.96kg, is adjusted to pH=3 with hydrochloric acid, cooled and filtered is dry, obtains fibrauretine crude product 835g；It is added in fibrauretine crude product
The ethanol solution 10kg and activated carbon 100g of volumetric concentration 85%, reflow treatment 25 minutes after heating fibrauretine crude product dissolving, while hot
Filtering, being stored at room temperature 24 hours makes crystallization, filtering, and crystal is placed in drying at 70 DEG C, obtains fibrauretine 520g, content 98.3%.
Claims (4)
1. a kind of producing the method that waste liquid of saltouing prepares fibrauretine using fibrauretine, which is characterized in that carry out according to the following steps：
（1）Fibrauretine produces waste liquid alkali of saltouing and adjusts pH=9~10, filtering；
（2）By step（1）Filtrate is by resin column, and after filtrate completion of the sample, the purifying water elution with 3~4 times of column volumes is miscellaneous
Matter；
（3）With the alkaloid on ethanol solution elution resin column, is differentiated with TLC thin layers, collect alkaloid section eluent；
（4）The alkaloid mixture containing jateorrhizine, Palmatine and jateorrhizine is obtained after the concentration of alkaloid section eluent；
（5）The tetrahydrofuran of 9~11 times of its quality of alkaloid mixture is dissolved, alkaloid mixture quality is then added
The iodomethane of 1~1.5 times of alkaloid mixture quality is added dropwise in 0.1~0.2 times of 4-dimethylaminopyridine, after the completion of reaction
Isometric purified water is added in reaction solution, is adsorbed by resin column after mixing, is then rushed with the purified water of 2~3 times of column volumes
Pillar is washed, then alkaloid is eluted with the ethanol solution of volumetric concentration 80~90%, alkaloid section eluent is collected, is concentrated under reduced pressure into
Concentrate quality is made a living 3~4 times of alkaloids mixture quality, and with hydrochloric acid tune pH=2~3, cold filtration, filter residue is dried to get Huang
Rattan element crude product；
（6）In step（5）Be added in fibrauretine crude product the volumetric concentration 80~90% of 10~12 times of its quality ethanol solution and its
The activated carbon that 0.1~0.2 times of quality, after heating fibrauretine crude product dissolving, reflow treatment 20~30min filterings, filtrate stands 24
Hour, it then filters, filter residue is dried to get fibrauretine.
2. according to claim 1 produce the method that waste liquid of saltouing prepares fibrauretine using fibrauretine, it is characterised in that：It is yellow
The sodium hydroxide that rattan element produces waste liquid mass concentration 35~45% of saltouing adjusts pH value.
3. according to claim 1 produce the method that waste liquid of saltouing prepares fibrauretine using fibrauretine, it is characterised in that：Tree
Resin is AB-8 or D101 resins in fat column.
4. according to claim 1 produce the method that waste liquid of saltouing prepares fibrauretine using fibrauretine, it is characterised in that：Step
Suddenly（3）The volumetric concentration of middle ethanol solution is 60~70%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110105353A (en) * | 2019-06-18 | 2019-08-09 | 云南润嘉药业有限公司 | Fibrauretine crystalline form and the preparation method and application thereof |
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Cited By (1)
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| CN110105353A (en) * | 2019-06-18 | 2019-08-09 | 云南润嘉药业有限公司 | Fibrauretine crystalline form and the preparation method and application thereof |
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