CN102702189A - Application of silica gel in purifying process of tetrahydro berberrubine - Google Patents
Application of silica gel in purifying process of tetrahydro berberrubine Download PDFInfo
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- CN102702189A CN102702189A CN201210150965XA CN201210150965A CN102702189A CN 102702189 A CN102702189 A CN 102702189A CN 201210150965X A CN201210150965X A CN 201210150965XA CN 201210150965 A CN201210150965 A CN 201210150965A CN 102702189 A CN102702189 A CN 102702189A
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- nandinine
- berberrubine
- silica gel
- solid
- column chromatography
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Abstract
The invention discloses application of 200-300-mesh column chromatography silica gel in a purifying process of tetrahydro berberrubine. In the prior art, the tetrahydro berberrubine is prepared by reducing berberrubine through sodium borohydride, and products obtained by reaction have dull color and low purity. A purifying method is convenient to operate, and the tetrahydro berberrubine obtained by the purifying method is nearly white in color and has purity as high as 99.6%.
Description
Technical field
The present invention relates to the application of a kind of silica gel in Nandinine is refining, particularly silica gel kind, Nandinine preparation method, and the solid-liquid ratio of silica gel and Nandinine chloroformic solution.
Background technology
Nandinine (Tetrahydroberberrubine) has pharmacologically actives such as anxiety, antidepressant and arrhythmia.Compound method is two types at present: one type is complete synthesis, and another kind of is semi-synthetic.The total synthesis method complex process, production cost is high.The semi-synthesis method reactions step is few, and reaction conditions is gentle, operate easier, low production cost, suitable industrialized production.Therefore, select semi-synthesis method to prepare Nandinine.With Yan Suan Xiao ?alkali (Umbellatine) be reaction raw materials, through 200 ℃ the decompression demethylating reactions prepare berberrubine, then berberrubine is dissolved in methyl alcohol and can makes title product with sodium borohydride reduction.In reduction reaction, Nandinine can constantly be separated out along with the carrying out of reaction owing to solubleness in methyl alcohol is lower, and therefore, suction filtration can obtain product after reaction finished.In the Nandinine of this method preparation inclusion impurity such as reaction raw materials, the product color is dark, purity is not high, needs further refining.At present, simple recrystallization or extraction process are handled, and the color of product and purity are all undesirable, and silica gel column chromatography, the product loss amount is big and process is complicated.Therefore selecting suitable process for purification is the important step among the Nandinine preparation technology.
Summary of the invention
The invention discloses the application of a kind of silica gel in the Nandinine process for refining, target is to remove look and improve product purity.
This experiment provides following technical scheme, and concrete grammar is following:
Get Nandinine bullion 5.00～10.00g with dissolved in chloroform, in chloroformic solution, add the removal of impurities sorbent material, stir the back suction filtration, get filtrating and reclaim solvent, the gained solid is with re-crystallizing in ethyl acetate.
(W, unit: gram) (V, unit: milliliter) than being 1: 1～1: 10 (W/V), silica gel and chloroformic solution solid-liquid ratio are 1: 1.25～1: 10 (W/V) to volume for Nandinine and chloroform quality.
Embodiment
The present invention is directed to the process for purification of Nandinine, investigated multiple removal of impurities sorbent material and sorbent material consumption.
Through following experimental example technology characteristics of the present invention is detailed further.
Experimental example
Medicine and reagent:
Trichloromethane; ETHYLE ACETATE; Glacial acetic acid min. 99.5; Triethylamine; Acetonitrile; 60～100 order column chromatography silica gels; 100～200 order column chromatography silica gels; 200～300 order column chromatography silica gels; 300～400 order column chromatography silica gels; D101 type macroporous resin; Gac; Zeyssatite; Aluminum oxide
Laboratory apparatus:
The Agilent1100 high performance liquid chromatograph; Chromatographic column: Hedera ODS-2 type C18 chromatographic column (250mm * 4.6mm, 5 μ m); 85-1 type magnetic stirring apparatus (Shanghai will prestige Electrical Appliances Co., Ltd); Rotatory evaporator RE-52 (Shanghai Yarong Biochemical Instrument Plant); SH2-D (III) circulation ability of swimming vacuum pump (Gongyi City magnificent instrument of son Ltd)
(1) screening of removal of impurities sorbent material
Get Nandinine bullion 2.00g, with the 10ml dissolved in chloroform, add an amount of removal of impurities sorbent material and stir the back suction filtration, filtrating is reclaimed solvent and dry, uses re-crystallizing in ethyl acetate again.Through the refining result of different removal of impurities sorbent materials each other relatively and with the refining result's of simple recrystallization method comparison, analysis-by-synthesis output, color and purity are confirmed best removal of impurities sorbent material.
Color detection is with reference to " 2010 editions two appendix XI A of Chinese pharmacopoeia solution colour test procedure, first method respectively with water dissolution, compares products therefrom with corresponding look brown-red solution.Concrete operation method is following: get a certain amount of sample (THBru bullion) and be dissolved in water, place the 25mL nessler colorimetric tube, thin up is to 10mL.Other gets the standard color solution 10mL of specified hue and look number, places another nessler colorimetric tube, before two pipes place white background simultaneously, looks squarely observation, and trial-product pipe color must not compare darker with the contrast QC.Reddish brown tone stock solution prescription: colorimetric is with NSC 51149 liquid 22.5mL, and colorimetric is used potassium dichromate solution 12.5mL, and colorimetric is used copper sulfate solution 20.0mL, and water 45.0mL shakes up promptly and gets.Table 1 is seen in the preparation of various looks number reddish brown tone standard color solution
The preparation of the various looks of table 1 number reddish brown tone standard color solution
Purity detects with HPLC.Chromatographic condition: chromatographic column: Hedera ODS-2 chromatographic column (250 * 4.6mm, 5 μ m); Moving phase: 0.6% Glacial acetic acid min. 99.5,0.06% triethylamine aqueous solution-acetonitrile (68: 32); Flow velocity: 1.0mL/min; Detect wavelength: 285nm.
Table 2 removal of impurities sorbent material The selection result
Can get by above experimental result; Product purity after 200～300 order column chromatography silica gels are refining is high, yield is high, of light color, after 300～400 order column chromatography silica gels are refining, though product purity and color are desirable; But because adsorption is stronger; Major impurity berberrubine polarity is slightly larger than Nandinine, also can adsorb Nandinine in the time of the silica gel adsorption berberrubine, causes the product yield to reduce.So choose 200～300 order column chromatography silica gels as the removal of impurities sorbent material.
(2) removal of impurities sorbent material consumption is investigated
Method is with removal of impurities sorbent material screening item, and the removal of impurities sorbent material is 200～300 order column chromatography silica gels, and silica gel (200～300 order) consumption is respectively 1g, 2g, 4g, 6g, 8g.
Table 3 silica gel consumption is investigated
Can be got by above experimental result, when silica gel add-on during greater than 4g, product purity and color are desirable, simultaneously can adsorption production but the silica gel consumption is excessive, and yield is reduced.And the silica gel add-on is during less than 4g, and the product color is darker, and purity is lower.So confirm that silica gel and chloroformic solution solid-liquid ratio are 1: 2.5 (W/V), this moment, refining effect was best.
Experimental result
Pass through The effects; Final definite removal of impurities sorbent material is 200～300 order column chromatography silica gels, and silica gel and chloroformic solution solid-liquid ratio are 1: 2.5 (W/V), after silica gel adsorption is refining; Final product Nandinine color is almost white, and purity can reach 99.6%.
Claims (3)
1. the application of silica gel in the Nandinine process for refining, its characteristic comprises following content:
The first step (preparation of Nandinine): getting hydrochloric acid berberrubine 5.00～10.00g, is solvent with methyl alcohol, and solid-liquid ratio is 1: 20～1: 30 (W/V).55～65 ℃ are back to whole dissolvings, in reaction solution, add Peng Qinghuana 0.40～0.80g, have solid to generate after reaction finishes, and suction filtration gets the cervinus powder behind the filtration cakes torrefaction.
Second step (making with extra care of Nandinine): get Nandinine bullion 5.00～10.00g, with dissolved in chloroform, solid-liquid ratio is 1: 1～1: 10 (W/V).In chloroformic solution, add the removal of impurities sorbent material, stir the back suction filtration, get filtrating and reclaim solvent and dry, with re-crystallizing in ethyl acetate.
2. select 200～300 order column chromatography silica gels for use according to the said removal of impurities sorbent material of claim 1.
3. be 1: 1.25～1: 10 (W/V) according to said 200～300 order column chromatography silica gels of claim 1 and chloroformic solution solid-liquid ratio.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210150965XA CN102702189A (en) | 2012-05-16 | 2012-05-16 | Application of silica gel in purifying process of tetrahydro berberrubine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201210150965XA CN102702189A (en) | 2012-05-16 | 2012-05-16 | Application of silica gel in purifying process of tetrahydro berberrubine |
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| CN102702189A true CN102702189A (en) | 2012-10-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201210150965XA Pending CN102702189A (en) | 2012-05-16 | 2012-05-16 | Application of silica gel in purifying process of tetrahydro berberrubine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011006000A1 (en) * | 2009-07-08 | 2011-01-13 | Haiyan Liu | Berberine derivatives useful for modulating lipid levels and their methods of synthesis |
| CN102000074A (en) * | 2010-10-26 | 2011-04-06 | 中国人民解放军军事医学科学院基础医学研究所 | Application of tetrahydroberberrubine in preparation of medicines for curing schizophrenia |
-
2012
- 2012-05-16 CN CN201210150965XA patent/CN102702189A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011006000A1 (en) * | 2009-07-08 | 2011-01-13 | Haiyan Liu | Berberine derivatives useful for modulating lipid levels and their methods of synthesis |
| CN102000074A (en) * | 2010-10-26 | 2011-04-06 | 中国人民解放军军事医学科学院基础医学研究所 | Application of tetrahydroberberrubine in preparation of medicines for curing schizophrenia |
Non-Patent Citations (1)
| Title |
|---|
| 张海峰等: "四氢小檗红碱的化学拆分研究", 《药学进展》, vol. 34, no. 10, 31 December 2010 (2010-12-31), pages 459 - 462 * |
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Application publication date: 20121003 |