CN104497004A - Method for preparing swertia lactone I-K - Google Patents
Method for preparing swertia lactone I-K Download PDFInfo
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- CN104497004A CN104497004A CN201410839349.4A CN201410839349A CN104497004A CN 104497004 A CN104497004 A CN 104497004A CN 201410839349 A CN201410839349 A CN 201410839349A CN 104497004 A CN104497004 A CN 104497004A
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- swerilactone
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- swertiamarin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
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Abstract
The invention discloses a method for preparing swertia lactone I-K. The method comprises the following steps: with swertiamarin as a raw material, converting the swertiamarin via heat treatment to generate a large amount of swertia lactone compounds, and separating the converted products through silica gel, Rp-18, MCI-gel fillers to obtain the swertia lactone I-K. Compared with the existing methods of extracting the swertia lactone compounds from swertia mileensis plant, the chemical conversion method in the invention is short in production period and is suitable for mass production, and the purity of the obtained product is high; moreover, the swertiamarin widely exists in a variety of plants, so that the source is wide. The problem that the swertia lactone I-K is unlikely to achieve industrial production by a plant extraction method due to a low content in plants is solved.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology, be specifically related to the preparation method of a kind of swerilactone I ~ K.
Background technology
Herba Swertiae bimaculatae lactone be the many chiralitys of a class, high oxidation, high thick and complex construction natural product, majority has anti-hepatitis B virus activities, is in recent years separated from Antihepatitis medicament Mile Swertia Herb and obtains.This constituents is very humble at plant materials content, does not possess industrialization production and commercial applications value, because its complex structure does not also obtain by chemosynthesis.
Chinese patent (application number is 201010587969.5) " swerilactone H ~ K; its medical composition and its use " discloses the Preparation method and use of 4 Herba Swertiae bimaculatae lactone compounds: by after Mile Swertia Herb herb drying and crushing by the easy refluxing extraction of ethanol, suspend in water after extracting solution concentrating under reduced pressure, use sherwood oil, ethyl acetate and n-butanol extraction successively, ethyl acetate portion is used repeatedly through silica gel column chromatography, separation obtains 4 Herba Swertiae bimaculatae lactone compounds, gained compound amount is few and the production cycle is long, is difficult to industrialization and produces.Therefore, a kind of method providing industrialization easy and simple to handle, with low cost to prepare Herba Swertiae bimaculatae lactone is significant for applying of Herba Swertiae bimaculatae lactone.
Summary of the invention
The object of the present invention is to provide the preparation method of a kind of swerilactone I ~ K.
The object of the present invention is achieved like this, comprises the following steps:
A, get swertiamarin, add the water of weight ratio 1 ~ 20 times, obtain conversion fluid in more than 80 DEG C backflow 5 ~ 7h to swertiamarin completely dissolve;
B, by conversion fluid cool, filter obtain filtrate and filter residue, 80 ~ 120 object silica gel mixed samples of filter residue weight ratio 0.1 ~ 2 times are added in filter residue, upper silicagel column, gradient elution is carried out with the sherwood oil-acetone soln of volume proportion 15 ~ 3:1, gradient elution is carried out again with the chloroform-methanol of volume proportion 20 ~ 0:1, elutriant is collected in TLC monitoring, is separated and obtains 14 component A ~ N;
C, get wherein M part, add 80 ~ 120 object silica gel mixed samples of weight ratio 0.1 ~ 2 times, upper silicagel column, carries out gradient elution with the chloroform-acetone solution of volume proportion 10 ~ 2:1, and elutriant is collected in TLC monitoring, is separated and obtains 17 part M1 ~ M17;
D, get M13 part, upper silicagel column, carry out gradient elution with the chloroform-acetone solution of volume proportion 8 ~ 2:1, then with the petroleum ether-ethyl acetate wash-out of volume proportion 1:1.3, elutriant concentrating under reduced pressure obtains swerilactone I;
E, get M14 part, obtain swerilactone J and swerilactone K through separation and purification.
Beneficial effect of the present invention:
The present invention adopts swertiamarin to be raw material, makes it transform by thermal treatment, produces a large amount of Herba Swertiae bimaculatae lactone compounds, and converted product is separated through silica gel, Rp-18, MCI-gel filler, obtains swerilactone I ~ K.With existing extract from Mile Swertia Herb plant prepare Herba Swertiae bimaculatae lactone compound method compared with, chemical transformation of the present invention is with short production cycle, can carry out producing in enormous quantities, products obtained therefrom purity is high; And swertiamarin is extensively present in various plants, wide material sources.Solve because swerilactone I ~ K content in plant is low, be difficult to a difficult problem of being carried out industrialization production by plant extraction method.
Embodiment
Below in conjunction with embodiment, the present invention is further illustrated, but limited the present invention never in any form, and any conversion done based on training centre of the present invention or replacement, all belong to protection scope of the present invention.
The preparation method of swerilactone I ~ K of the present invention, comprises the following steps:
A, get swertiamarin, add the water of weight ratio 1 ~ 20 times, obtain conversion fluid in more than 80 DEG C backflow 5 ~ 7h to swertiamarin completely dissolve;
B, by conversion fluid cool, filter obtain filtrate and filter residue, 80 ~ 120 object silica gel mixed samples of filter residue weight ratio 0.1 ~ 2 times are added in filter residue, upper silicagel column, gradient elution is carried out with the sherwood oil-acetone soln of volume proportion 15 ~ 3:1, gradient elution is carried out again with the chloroform-methanol of volume proportion 20 ~ 0:1, elutriant is collected in TLC monitoring, is separated and obtains 14 component A ~ N;
C, get wherein M part, add 80 ~ 120 object silica gel mixed samples of weight ratio 0.1 ~ 2 times, upper silicagel column, carries out gradient elution with the chloroform-acetone solution of volume proportion 10 ~ 2:1, and elutriant is collected in TLC monitoring, is separated and obtains 17 part M1 ~ M17;
D, get M13 part, upper silicagel column, carry out gradient elution with the chloroform-acetone solution of volume proportion 8 ~ 2:1, then with the petroleum ether-ethyl acetate wash-out of volume proportion 1:1.3, elutriant concentrating under reduced pressure obtains swerilactone I;
E, get M14 part, obtain swerilactone J and swerilactone K through separation and purification.
The temperature of the backflow described in step A is 90 ~ 100 DEG C.
The monitoring of the swertiamarin completely dissolve described in step A adopts TLC monitoring.
The volume proportion of the sherwood oil-acetone soln described in step B is 15:1,10:1,8:1,5:1,3:1.
The volume proportion of the chloroform-methanol described in step B is 20:1,15:1,10:1,5:1,3:1,0:1.
The volume proportion of the chloroform-acetone solution described in step C is 10:1,7:1,5:1,2:1.
The volume proportion of the chloroform-acetone solution described in D step is 8:1,6:1,4:1,2:1.
Separation and purification described in E step adopts to be separated through Rp-18, MCI-gel successively, carries out gradient elution with the methanol-water solution of volume proportion 0 ~ 100:100 ~ 0.
The volume proportion of described methanol-water solution is 1:100,20:80,40:60,60:40,80:20,100:0.
With embodiment, the present invention is further described below:
Embodiment 1
Get swertiamarin 20kg, add the water of 15 times of weight, be warming up to 95 DEG C and carry out conversion reaction, after testing after swertiamarin completely dissolve, reaction stops, and is cooled to room temperature, filters to obtain filter residue; The silica gel mixed sample of 1.5 times of weight is added in filter residue, silicagel column is loaded after oven dry, sherwood oil-acetone (15:1,10:1,8:1,5:1,3:1) 5 gradients are first used to carry out wash-out, use chloroform-methanol (20:1,15:1,10:1,5:1,3:1,0:1) 6 gradients to carry out wash-out again, obtain 14 component A ~ N.Component M is separated through silica gel column chromatography, adopts chloroform-acetone (10:1,7:1,5:1,2:1) 4 gradients to carry out wash-out, obtain 17 part M
1~ M
17; Get M
13part, is separated through silica gel column chromatography, uses chloroform-acetone (8:1,6:1,4:1,2:1) 4 gradients to carry out wash-out, use petroleum ether-ethyl acetate (1:1.3) wash-out more successively, obtain 4.63 g swerilactone Is; Get M
14part, is separated through Rp-18, MCI-gel successively, adopts methanol-water (1:100,20:80,40:60,60:40,80:20,100:0) 6 gradients to carry out wash-out, obtains 57.76mg swerilactone J, 600.88mg swerilactone K.Swerilactone I, J, K purity are be not 98.7%, 97.6%, 98.8% after testing.
Embodiment 2
Get swertiamarin 15kg, add the water of 20 times of weight, be warming up to 100 DEG C and carry out conversion reaction, after testing after swertiamarin completely dissolve, reaction stops, and is cooled to room temperature, filters to obtain filter residue; The silica gel mixed sample of 2 times of weight is added in filter residue, silicagel column is loaded after oven dry, sherwood oil-acetone (15:1,10:1,8:1,5:1,3:1) 5 gradients are first used to carry out wash-out, use chloroform-methanol (20:1,15:1,10:1,5:1,3:1,0:1) 6 gradients to carry out wash-out again, obtain 14 component A ~ N.Component M is separated through silica gel column chromatography, adopts chloroform-acetone (10:1,7:1,5:1,2:1) 4 gradients to carry out wash-out, obtain 17 part M
1~ M
17; Get M
13part, is separated through silica gel column chromatography, uses chloroform-acetone (8:1,6:1,4:1,2:1) 4 gradients to carry out wash-out, use petroleum ether-ethyl acetate (1:1.3) wash-out more successively, obtain 3.67g swerilactone I; Get M
14part, is separated through Rp-18, MCI-gel successively, adopts methanol-water (1:100,20:80,40:60,60:40,80:20,100:0) 6 gradients to carry out wash-out, obtains 44.32mg swerilactone J, 451.66mg swerilactone K.Swerilactone I, J, K purity are be not 98.2%, 98.6%, 97.8% after testing.
Embodiment 3
Get swertiamarin 10kg, add the water of 5 times of weight, be warming up to 90 DEG C and carry out conversion reaction, after testing after swertiamarin completely dissolve, reaction stops, and is cooled to room temperature, filters to obtain filter residue; The silica gel mixed sample of 2 times of weight is added in filter residue, silicagel column is loaded after oven dry, sherwood oil-acetone (15:1,10:1,8:1,5:1,3:1) 5 gradients are first used to carry out wash-out, use chloroform-methanol (20:1,15:1,10:1,5:1,3:1,0:1) 6 gradients to carry out wash-out again, obtain 14 component A ~ N.Component M is separated through silica gel column chromatography, adopts chloroform-acetone (10:1,7:1,5:1,2:1) 4 gradients to carry out wash-out, obtain 17 part M
1~ M
17; Get M
13part, is separated through silica gel column chromatography, uses chloroform-acetone (8:1,6:1,4:1,2:1) 4 gradients to carry out wash-out, use petroleum ether-ethyl acetate (1:1.3) wash-out more successively, obtain 2.43g swerilactone I; Get M
14part, is separated through Rp-18, MCI-gel successively, adopts methanol-water (1:100,20:80,40:60,60:40,80:20,100:0) 6 gradients to carry out wash-out, obtains 44.32mg swerilactone J, 299.32mg swerilactone K.Swerilactone I, J, K purity are be not 98.9%, 97.6%, 98.8% after testing.
Claims (9)
1. a preparation method of swerilactone I ~ K, is characterized in that comprising the following steps:
A, get swertiamarin, add the water of weight ratio 1 ~ 20 times, obtain conversion fluid in more than 80 DEG C backflow 5 ~ 7h to swertiamarin completely dissolve;
B, by conversion fluid cool, filter obtain filtrate and filter residue, 80 ~ 120 object silica gel mixed samples of filter residue weight ratio 0.1 ~ 2 times are added in filter residue, upper silicagel column, gradient elution is carried out with the sherwood oil-acetone soln of volume proportion 15 ~ 3:1, gradient elution is carried out again with the chloroform-methanol of volume proportion 20 ~ 0:1, elutriant is collected in TLC monitoring, is separated and obtains 14 component A ~ N;
C, get wherein M part, add 80 ~ 120 object silica gel mixed samples of weight ratio 0.1 ~ 2 times, upper silicagel column, carries out gradient elution with the chloroform-acetone solution of volume proportion 10 ~ 2:1, and elutriant is collected in TLC monitoring, is separated and obtains 17 part M1 ~ M17;
D, get M13 part, upper silicagel column, carry out gradient elution with the chloroform-acetone solution of volume proportion 8 ~ 2:1, then with the petroleum ether-ethyl acetate wash-out of volume proportion 1:1.3, elutriant concentrating under reduced pressure obtains swerilactone I;
E, get M14 part, obtain swerilactone J and swerilactone K through separation and purification.
2. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the temperature of the backflow described in step A is 90 ~ 100 DEG C.
3. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the monitoring of the swertiamarin completely dissolve described in step A adopts TLC monitoring.
4. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the volume proportion of the sherwood oil-acetone soln described in step B is 15:1,10:1,8:1,5:1,3:1.
5. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the volume proportion of the chloroform-methanol described in step B is 20:1,15:1,10:1,5:1,3:1,0:1.
6. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the volume proportion of the chloroform-acetone solution described in step C is 10:1,7:1,5:1,2:1.
7. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the volume proportion of the chloroform-acetone solution described in D step is 8:1,6:1,4:1,2:1.
8. the preparation method of swerilactone I ~ K according to claim 1, is characterized in that the separation and purification described in E step adopts to be separated through Rp-18, MCI-gel successively, carries out gradient elution with the methanol-water solution of volume proportion 0 ~ 100:100 ~ 0.
9. the preparation method of swerilactone I ~ K according to claim 8, is characterized in that the volume proportion of described methanol-water solution is 1:100,20:80,40:60,60:40,80:20,100:0.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410839349.4A CN104497004A (en) | 2014-12-30 | 2014-12-30 | Method for preparing swertia lactone I-K |
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| CN201410839349.4A CN104497004A (en) | 2014-12-30 | 2014-12-30 | Method for preparing swertia lactone I-K |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005002056A (en) * | 2003-06-12 | 2005-01-06 | Pola Chem Ind Inc | Dendrite growth promoter of melanocyte, and cosmetic containing the same |
| CN102532156A (en) * | 2010-12-15 | 2012-07-04 | 中国科学院昆明植物研究所 | Swerilactones H-K, 1-4 and medicinal composition and application thereof |
| CN103265536A (en) * | 2013-05-24 | 2013-08-28 | 南京泽朗医药科技有限公司 | Preparation method of swertisin |
| CN103265521A (en) * | 2013-05-27 | 2013-08-28 | 南京泽朗医药科技有限公司 | Preparation method of demethylated beilidifolin |
-
2014
- 2014-12-30 CN CN201410839349.4A patent/CN104497004A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005002056A (en) * | 2003-06-12 | 2005-01-06 | Pola Chem Ind Inc | Dendrite growth promoter of melanocyte, and cosmetic containing the same |
| CN102532156A (en) * | 2010-12-15 | 2012-07-04 | 中国科学院昆明植物研究所 | Swerilactones H-K, 1-4 and medicinal composition and application thereof |
| CN103265536A (en) * | 2013-05-24 | 2013-08-28 | 南京泽朗医药科技有限公司 | Preparation method of swertisin |
| CN103265521A (en) * | 2013-05-27 | 2013-08-28 | 南京泽朗医药科技有限公司 | Preparation method of demethylated beilidifolin |
Non-Patent Citations (4)
| Title |
|---|
| CHANG-AN GENG ET AL.: ""Anti-Hepatitis B Virus Active Lactones from the Traditional Chinese Herb: Swertia mileensis"", 《CHEM. EUR. J.》, vol. 17, 1 March 2011 (2011-03-01), pages 3893 - 3903 * |
| 姚旭东: ""青叶胆药材中獐牙菜苦苷的热转化研究"", 《中国学位论文全文数据库》, 9 December 2014 (2014-12-09) * |
| 姚远鹏: ""獐牙菜苦苷在水中热转化产物脂溶性部分的化学成分继续研究"", 《中国学位论文全文数据库》, 9 December 2014 (2014-12-09) * |
| 杜盛楠: ""獐牙菜苦苷热转化产物水溶性成分的化学研究"", 《中国学位论文全文数据库》, 9 December 2014 (2014-12-09) * |
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