CN101942003A - Compound and preparation method thereof - Google Patents
Compound and preparation method thereof Download PDFInfo
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- CN101942003A CN101942003A CN2009100885254A CN200910088525A CN101942003A CN 101942003 A CN101942003 A CN 101942003A CN 2009100885254 A CN2009100885254 A CN 2009100885254A CN 200910088525 A CN200910088525 A CN 200910088525A CN 101942003 A CN101942003 A CN 101942003A
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Abstract
The invention relates to a compound and a preparation method thereof. The compound has a structural formula. The compound is prepared by extracting blood fat recovery capsules, and has HMG-CoA reductase inhibiting activity effect.
Description
Technical field
The present invention relates to a kind of compound and preparation method thereof, particularly have compound of HMG-CoA reductase active effect and preparation method thereof.
Background technology
Endogenous cholesterol is synthetic at liver, in hepatocellular tenuigenin, finish through 26 step biosynthesizing steps by acetate, wherein 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme is the rate-limiting enzyme in this building-up process, be key one step of endogenous cholesterol in synthetic, the HMG-CoA reductase inhibitor reduces endogenic cholesterol by the activity that suppresses the HMG-CoA reductase enzyme, reaches the effect of transferring blood fat.Really.
At present, Chang Yong HMG-CoA reductase inhibitor has statinses such as lovastatin, Pravastatin, Simvastatin, fluvastatin.Lovastatin (Lovastatin) is the mould meta-bolites that extracts from the monascus ruber nutrient solution.Be hydrolyzed after oral, lactonic ring is opened, and becomes activated alcohol acid, is that first is applied to clinical effective HMG-CoA reductase inhibitor.After oral, 30% is absorbed also, and metabolism is activated open loop alcohol acid, and 2～4h effect reaches the peak.Plasma protein binding ratio 95% mainly is distributed in liver, is kidney, spleen, testis, suprarenal gland etc. secondly.83% through bile excretion.T 1/2 about 3h.Pravastatin (pravastatin) itself has open loop structure, and therefore, the original shape medicine promptly has activity, and rapid-action, the long-term treatment efficacy stability.The absorption reaction of resene medicine can reduce the bioavailability of this medicine, so during combined utilization, certain hour at interval.This medicine prototype and metabolite all can be through kidney and bile excretions, liver or renal insufficiency person, but other potential discharge capacity is transferred on compensatory ground, so do not need decrement.(warfarin) share with warfarin, do not influence the latter's anticoagulation.Simvastatin (simvastatin) is the derivative of lovastatin, and non-activity own is converted into just tool activity of beta-hydroxy acid after the oral absorption.Its effect that reduces TC and LDL-C is stronger than lovastatin.Fluvastatin (fluvastatin) constructional feature is different with aforementioned medicine, for having the first hydroxyl pentanedioic acid lactone derivatives of fluorobenzene indoles, the substrate of its indole ring simulation HMG-CoA reductase enzyme, the activity of this enzyme of competitive inhibition generates the precursor of cholesterol mevalonic acid and reduces; Its mevalonolactone chain is then simulated the enzymatic reaction product mevalonic acid, disturbs latter's synthetic cholesterol.Untoward reaction and pravastatin are similar.But share than other statins safety with ciclosporin (ciclosporin), digoxin, warfarin, antihypertensive drug, H2 receptor antagonist and non-steroidal anti-inflammatory drugs.Zarator (atorvastatin) is the most effective statins of new synthetic.Different with most of statins, this medicine is still effective to the homozygote familial hyerlipoproteinemia.Untoward reaction is light, and modal is gastrointestinal reaction, this reaction and dosage indifference.
Summary of the invention
One object of the present invention is to disclose the compound of a kind of HMG-CoA of having reductase active effect; Another object of the present invention is the method for open this compound of preparation.
Structural formula of compound of the present invention is as follows:
This compound name is called 3,16,20,22,23,25-hexahydroxy-ergosterol
The preparation method of The compounds of this invention is:
Get XUEZHIKANG JIAONANG (standard numbering: content WS3-193 (X-183)-97 (Z)), with 3-5 times of weight chloroform supersound extraction 2-5 time, 20-40min/ time; United extraction liquid reclaims solvent, gets chloroform extract; Get silica gel column chromatography on the chloroform extract, (100-0: 0-100) gradient elution gets 90: 10 chloroform-methanol wash-out parts with chloroform-methanol; Chloroform-methanol wash-out part was with 90 in 90: 10: 10-50: 50 chloroform-methanol gradient elutions get 80: 20 chloroform-methanol wash-out parts; 80: 20 chloroform-methanol wash-out parts, (100-0: 0-100) eluent silica gel column chromatography repeatedly obtains crude product with petroleum ether-ethyl acetate; With C-18 is stationary phase, methanol-water gradient elution (0-100: 100-0) carry out high performance liquid chromatograph and partly prepare purifying, obtain pure product (purity 98%).
The preparation method of The compounds of this invention is preferably:
Get the XUEZHIKANG JIAONANG content, with 4 times of weight chloroform supersound extraction 3 times, 30min/ time; United extraction liquid reclaims solvent, gets chloroform extract; Get silica gel column chromatography on the chloroform extract, (100-0: 0-100) gradient elution gets 90: 10 chloroform-methanol wash-out parts with chloroform-methanol; Chloroform-methanol wash-out part was with 90 in 90: 10: 10-50: 50 chloroform-methanol gradient elutions get 80: 20 chloroform-methanol wash-out parts; 80: 20 chloroform-methanol wash-out parts, (100-0: 0-100) eluent silica gel column chromatography repeatedly obtains crude product with petroleum ether-ethyl acetate; With C-18 is stationary phase, methanol-water gradient elution (0-100: 100-0) carry out high performance liquid chromatograph and partly prepare purifying, obtain compound.
Following experimental example is used to further specify the present invention.
Experimental example 1 The compounds of this invention structure is identified
These pure product are measured with the micro-determinator of Kofler, and fusing point is 135～137 ℃ of mp; The PEModel343 polarimeter is measured, and specific rotation is [α]
20 D-126.8 ° (c 0.101, CHCl
3); Finnigan Advantage Max mass spectrograph, the Bruker NMR spectrometer with superconducting magnet is measured, and draws the molecular weight of this compound through electron bombardment ion source-mass spectroscopy (EI-MS) analysis: 477 (M-1) 461 (M-OH) 427 (M-3*OH), molecular formula: C
28H
46O
6
NMR(DMSO，500MHz)：
According to above data, identify that this this compound is 3,16,20,22,23,25-hexahydroxy-ergosterol.
The HMG-CoA reductase active of experimental example 2 The compounds of this invention:
With 75% dissolve with ethanol, concentration is 2mg/ml with The compounds of this invention.Cumulative volume is 200 μ l in the mensuration system, the concentration of each composition is: Kcl 200mM, KH2PO4 160mM, EDTA 4mM, DTT10mM, the concentration of NADPH and HMG-CoA is respectively 200 μ M and 50 μ M, pH6.8, enzyme adds in right amount, and enzyme inhibitors adds 5 μ l (the blank group adds 5 μ l, 75% ethanol), the dynamic change of monitoring OD340 under 37 ℃ of conditions on the Versamax microplate reader.
The result is as follows:
Above result shows, hexahydroxy-ergosterol and ergosterol all have certain HMG-CoA reductase enzyme restraining effect external.
Embodiment
Embodiment:
Get XUEZHIKANG JIAONANG content 2kg, with 4 times of weight chloroform supersound extraction 3 times, 30min/ time; United extraction liquid reclaims solvent, gets chloroform extract; Get chloroform extract 250g and go up silica gel column chromatography, (100-0: 0-100) gradient elution gets 90: 10 chloroform-methanol wash-out parts with chloroform-methanol; Chloroform-methanol wash-out part was with 90 in 90: 10: 10-50: 50 chloroform-methanol gradient elutions get 80: 20 chloroform-methanol wash-out parts; 80: 20 chloroform-methanol wash-out parts, (100-0: 0-100) eluent silica gel column chromatography repeatedly obtains crude product 47mg with petroleum ether-ethyl acetate; With C-18 is stationary phase, methanol-water gradient elution (0-100: 100-0) carry out high performance liquid chromatograph and partly prepare purifying, obtain the pure product of The compounds of this invention (purity 98%) 35mg.
Claims (3)
1. compound is characterized in that this structural formula of compound is:
2. the preparation method of compound as claimed in claim 1 is characterized in that this method is:
Get the XUEZHIKANG JIAONANG content, with 3-5 times of weight chloroform supersound extraction 2-5 time, 20-40min/ time; United extraction liquid reclaims solvent, gets chloroform extract; Get silica gel column chromatography on the chloroform extract, (100-0: 0-100) gradient elution gets 90: 10 chloroform-methanol wash-out parts with chloroform-methanol; Chloroform-methanol wash-out part was with 90 in 90: 10: 10-50: 50 chloroform-methanol gradient elutions get 80: 20 chloroform-methanol wash-out parts; 80: 20 chloroform-methanol wash-out parts, (100-0: 0-100) eluent silica gel column chromatography repeatedly obtains crude product with petroleum ether-ethyl acetate; With C-18 is stationary phase, methanol-water gradient elution (0-100: 100-0) carry out high performance liquid chromatograph and partly prepare purifying, promptly.
3. the preparation method of compound as claimed in claim 2 is characterized in that this method is:
Get the XUEZHIKANG JIAONANG content, with 4 times of weight chloroform supersound extraction 3 times, 30min/ time; United extraction liquid reclaims solvent, gets chloroform extract; Get silica gel column chromatography on the chloroform extract, (100-0: 0-100) gradient elution gets 90: 10 chloroform-methanol wash-out parts with chloroform-methanol; Chloroform-methanol wash-out part was with 90 in 90: 10: 10-50: 50 chloroform-methanol gradient elutions get 80: 20 chloroform-methanol wash-out parts; 80: 20 chloroform-methanol wash-out parts, (100-0: 0-100) eluent silica gel column chromatography repeatedly obtains crude product with petroleum ether-ethyl acetate; With C-18 is stationary phase, methanol-water gradient elution (0-100: 100-0) carry out high performance liquid chromatograph and partly prepare purifying, obtain compound.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100885254A CN101942003A (en) | 2009-07-09 | 2009-07-09 | Compound and preparation method thereof |
| PCT/CN2010/001027 WO2011003284A1 (en) | 2009-07-09 | 2010-07-09 | Compound and preparation method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100885254A CN101942003A (en) | 2009-07-09 | 2009-07-09 | Compound and preparation method thereof |
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|---|---|
| CN101942003A true CN101942003A (en) | 2011-01-12 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103172693A (en) * | 2011-12-26 | 2013-06-26 | 北京北大维信生物科技有限公司 | Sterol derivative, and preparation method and application thereof |
| WO2013097681A1 (en) * | 2011-12-26 | 2013-07-04 | 北京北大维信生物科技有限公司 | Sterols derivative, and preparation method and purpose thereof |
| CN103242417A (en) * | 2012-02-02 | 2013-08-14 | 北京北大维信生物科技有限公司 | Sterol derivative, and preparation method and application thereof |
| TWI580689B (en) * | 2012-02-02 | 2017-05-01 | 北京北大維信生物科技有限公司 | A sterol derivatives, preparation method and use thereof |
-
2009
- 2009-07-09 CN CN2009100885254A patent/CN101942003A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103172693A (en) * | 2011-12-26 | 2013-06-26 | 北京北大维信生物科技有限公司 | Sterol derivative, and preparation method and application thereof |
| WO2013097681A1 (en) * | 2011-12-26 | 2013-07-04 | 北京北大维信生物科技有限公司 | Sterols derivative, and preparation method and purpose thereof |
| CN104024270A (en) * | 2011-12-26 | 2014-09-03 | 北京北大维信生物科技有限公司 | Sterols Derivative, And Preparation Method And Purpose Thereof |
| US20150031657A1 (en) * | 2011-12-26 | 2015-01-29 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterols derivative, and preparation method and purpose thereof |
| CN103172693B (en) * | 2011-12-26 | 2016-01-27 | 北京北大维信生物科技有限公司 | A kind of sterol derivative, Preparation Method And The Use |
| US10889612B2 (en) | 2011-12-26 | 2021-01-12 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivatives and preparation method and uses thereof |
| US11634454B2 (en) | 2011-12-26 | 2023-04-25 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivatives and preparation method and uses thereof |
| US11845774B2 (en) | 2011-12-26 | 2023-12-19 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivatives and preparation method and uses thereof |
| US11845775B2 (en) | 2011-12-26 | 2023-12-19 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivatives and preparation method and uses thereof |
| CN103242417A (en) * | 2012-02-02 | 2013-08-14 | 北京北大维信生物科技有限公司 | Sterol derivative, and preparation method and application thereof |
| CN103242417B (en) * | 2012-02-02 | 2016-04-06 | 北京北大维信生物科技有限公司 | A kind of sterol derivative and preparation method thereof and application |
| TWI580689B (en) * | 2012-02-02 | 2017-05-01 | 北京北大維信生物科技有限公司 | A sterol derivatives, preparation method and use thereof |
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Application publication date: 20110112 |