CN101066948A - Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine - Google Patents
Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine Download PDFInfo
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- CN101066948A CN101066948A CN 200710028338 CN200710028338A CN101066948A CN 101066948 A CN101066948 A CN 101066948A CN 200710028338 CN200710028338 CN 200710028338 CN 200710028338 A CN200710028338 A CN 200710028338A CN 101066948 A CN101066948 A CN 101066948A
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- coculine
- tuduranine
- hydrogenated
- catalytic hydrogenation
- catalyst
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Abstract
The present invention discloses catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine. The process includes: 1. catalytically hydrogenating and reducing coculine into hydrogenated coculine in water or alcohol reaction solvent system under hydrogen pressure of 300-500 psi in the presence of Pd/C catalyst with 10 % Pd supported on active carbon or PtO2 catalyst; and 2. catalytically hydrogenating and reducing coculine into hydrogenated coculine in water or alcohol reaction solvent system under hydrogen pressure of 300-500 psi in the presence of Pd/C catalyst with Rh/Al2O3 catalyst with 5 % Rh supported on Al2O3 powder. Primary pharmacological and pharmacodynamic experiments show that the hydrogenated coculine has relatively high physiological activity.
Description
Technical field
The invention belongs to chemical pharmacy, be specifically related to the method that a kind of tuduranine catalytic hydrogenation reduction prepares hydrogenated coculine.
Background technology
Tuduranine be from the natural traditional Chinese medicine Stem of Orientoine, extract the effective alkaloid list plant amedica (medicinal its hydrochloride that mostly is) that exsomatizes arranged.Tuduranine treatment rheumatoid arthritis determined curative effect, total effective rate is about 85%, onset time is 2-3 week, takes an evident turn for the better after about 1 month.Tuduranine improves all more remarkable to treatment patient's hand and lower limb function, joint stiff time in morning, arthralgia, erythrocyte sedimentation rate and Rheumatoid factors, polyclonal etc., but using tuduranine medicine weak point is that pharmacological action is slow, must take medicine for a long time, oral administration biaavailability is lower, and the transformation period is shorter.It is worthy of note especially, after nearly 1/3 patient uses tuduranine, cause the allergic symptom of skin itching, limited the popularization of its application.With the stripped tuduranine of alkaloid list is parent, and it is the work with meaning that tuduranine is carried out the chemical results modification.This patent synthetic hydrogenated coculine has higher physiological activities through preliminary pharmacological effect experiment surface.
Summary of the invention
The purpose of this invention is to provide the method that a kind of tuduranine catalytic hydrogenation reduction prepares hydrogenated coculine.This method comprises:
(1) use 10%Pd loads on Pd/C catalyzer or the PtO on the gac
2Catalyzer is under the pressure of 300～500psi at hydrogen, and reaction solvent is in water or the alcoholic acid system, and the tuduranine catalytic hydrogenation is reduced into the dihydro tuduranine; As following formula I:
(2) use 5%Rh to load on Al
2O
3The Rh/Al of powder
2O
3Catalyzer is under the pressure of 300～500psi at hydrogen, is in water or the alcoholic acid system at reaction solvent, and the tuduranine catalytic hydrogenation is reduced into hydrogenated coculine such as following formula II:
Above-mentioned catalyst levels is 0.5～2% of a tuduranine.
Above-mentioned temperature of reaction can at room temperature be finished reaction process.
Above-mentioned tuduranine is natural list from tuduranine or natural list from the tuduranine hydrochloride.
Synthetic hydrogenated coculine of the present invention has higher physiological activities through preliminary pharmacological effect experiment surface.
Figure of description
Fig. 1 is the crystalline structure figure of hydrogenated coculine II of the present invention.
Embodiment
Below in conjunction with embodiment technical scheme of the present invention is further described.
1. tuduranine purifying
(1) recrystallization of tuduranine hydrochloride: get tuduranine hydrochloride (content 95%) 10 grams, under refluxing, be dissolved in about 170ml dehydrated alcohol, then solution is cooled to room temperature, leave standstill, separate out crystal, filter.Get white crystal 9.4 grams.
(2) the tuduranine hydrochloride changes into tuduranine: get tuduranine hydrochloride 2 grams of preparation, be dissolved in about 15ml distilled water (pH=7).Use 15%NH
3Water transfers solution system to pH=10 lentamente, uses CHCl again
3Extract 4 times (30ml * 4).Combining extraction liquid.The organic phase anhydrous K
2CO
3Dry about 40min filters, and rotary evaporation desolvates, and gets white solid 1.7 grams.
2. the preparation of dihydro tuduranine I
Stir in the 50ml autoclave at band, get the tuduranine 1g of above-mentioned preparation, ethanol 20ml, 0.1gPd/C (10%Pd loads on gac) catalyzer, pressurising hydrogen to 350psi, react at normal temperatures, and pressure no longer reduces (about 10 hours) to the reactor, get final product release hydrogen, stopped reaction.Desolvate, promptly get dihydro tuduranine (1), yield 100%.
3. the preparation of hydrogenated coculine II
Stir in the 50ml autoclave at band, get the tuduranine hydrochloride 1g of above-mentioned preparation, deionized water 15ml, 0.1g Rh/Al
2O
3(5%Rh loads on Al
2O
3Powder) catalyzer, pressurising hydrogen be to 400psi, reacts at normal temperatures that pressure no longer reduces (about 24 hours) to the reactor, gets final product release hydrogen, stopped reaction.Desolvate, promptly get hydrogenated coculine (2) ([α]
D 20° 11.3 (c=1, EtOH)), yield 100%.
Claims (4)
1. tuduranine catalytic hydrogenation reduction prepares the method for hydrogenated coculine, it is characterized in that:
(1) use 10%Pd loads on Pd/C catalyzer or the PtO on the gac
2Catalyzer is under the pressure of 300～500psi at hydrogen, and reaction solvent is in water or the alcoholic acid system, and the tuduranine catalytic hydrogenation is reduced into the dihydro sinomenium acutum; As following formula I:
(2) use 5%Rh to load on Al
2O
3The Rh/Al of powder
2O
3Catalyzer is under the pressure of 300～500psi at hydrogen, is in water or the alcoholic acid system at reaction solvent, and the tuduranine catalytic hydrogenation is reduced into hydrogenated coculine; As following formula II:
2. method according to claim 1 is characterized in that: above-mentioned catalyst levels is 0.5～2% of a tuduranine.
3. method according to claim 1 is characterized in that: above-mentioned temperature of reaction can at room temperature be finished reaction process.
4. method according to claim 1 is characterized in that: above-mentioned tuduranine is natural list from tuduranine or natural list from the tuduranine hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100283388A CN101066948B (en) | 2007-05-30 | 2007-05-30 | Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100283388A CN101066948B (en) | 2007-05-30 | 2007-05-30 | Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101066948A true CN101066948A (en) | 2007-11-07 |
| CN101066948B CN101066948B (en) | 2012-01-04 |
Family
ID=38879668
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100283388A Expired - Fee Related CN101066948B (en) | 2007-05-30 | 2007-05-30 | Catalytic hydrogenation and reduction process of coculine for preparing hydrogenated coculine |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011009015A1 (en) * | 2009-07-16 | 2011-01-20 | Mallinckrodt Inc. | (+) - morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| US8829020B2 (en) | 2009-07-16 | 2014-09-09 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| US10363251B2 (en) | 2009-07-16 | 2019-07-30 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| US10604488B2 (en) | 2009-07-16 | 2020-03-31 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3166560A (en) * | 1965-01-19 | G-vlkylmorpiiinan derivatives |
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2007
- 2007-05-30 CN CN2007100283388A patent/CN101066948B/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011009015A1 (en) * | 2009-07-16 | 2011-01-20 | Mallinckrodt Inc. | (+) - morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| JP2012533561A (en) * | 2009-07-16 | 2012-12-27 | マリンクロッド エルエルシー | (+)-Morphinan as an antagonist of Toll-like receptor 9 and its therapeutic use |
| US8829020B2 (en) | 2009-07-16 | 2014-09-09 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| US9518062B2 (en) | 2009-07-16 | 2016-12-13 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| US9527858B2 (en) | 2009-07-16 | 2016-12-27 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| US10363251B2 (en) | 2009-07-16 | 2019-07-30 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| US10604488B2 (en) | 2009-07-16 | 2020-03-31 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| US11142502B2 (en) | 2009-07-16 | 2021-10-12 | Mallinckrodt Llc | (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof |
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| Publication number | Publication date |
|---|---|
| CN101066948B (en) | 2012-01-04 |
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Granted publication date: 20120104 Termination date: 20130530 |