CN107793464A - A kind of preparation method of urso - Google Patents
A kind of preparation method of urso Download PDFInfo
- Publication number
- CN107793464A CN107793464A CN201610768367.7A CN201610768367A CN107793464A CN 107793464 A CN107793464 A CN 107793464A CN 201610768367 A CN201610768367 A CN 201610768367A CN 107793464 A CN107793464 A CN 107793464A
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- CN
- China
- Prior art keywords
- urso
- formula
- compound
- preparation
- obtains
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
The invention provides a kind of method for preparing urso, using 7 carbonyl lithocholates as raw material, catalytic hydrogenation, hydrolysis and recrystallization are carried out using zinc powder/ammonium formate system urso is made, optimize reaction scheme and process conditions, improve the purity and yield of product.
Description
Technical field
The present invention relates to a kind of preparation method of urso.
Background technology
Urso Ursodeoxycholic acid are as the principle active component contained by bear gall, clinically mainly
For treating various diseases in the liver and gallbladder and disease of digestive tract；The chemical name of urso is 3 α, 7-5 β of beta-dihydroxy-cholic acid,
Its structural formula is：
The synthetic route about urso, preparation method are more in current all kinds of patents and document, and traditional bear goes
The preparation method of oxycholic acid typically from bear it is living take extract after bear gall it is isolated；, should due to the requirement to save the wild animals
Method is substantially impossible, in recent years, with animal Cholic acids (including：Cholic acid, chenodeoxycholic acid, hyocholic acid, hyodesoxycholic acid
Deng) for raw material synthetic method more grow up.
The content of the invention
The present invention finds out following syntheti c route on the basis of existing technology, in practice：
By the reduction to carbonyls, ester group is then sloughed, obtains urso.
The invention aims to overcome weak point of the prior art, there is provided a kind of new to prepare urso
Method, optimize reaction scheme and process conditions, improve the purity and yield of product.
The present invention provides a kind of preparation synthetic method of urso
This method comprises the following steps：
The preparation of urso is achieved by the steps of in the present invention：
Step 1：The compound of formula 3 carries out catalytic hydrogenation using zinc powder/ammonium formate system and obtains the compound of formula 2；
Step 2：The compound of formula 2 sloughs ester group, obtains the ursodeoxycholic acid crude of formula 1；
Step 3：The ursodeoxycholic acid crude for the formula 1 that step 2 obtains is recrystallized to give the urso of sterling.
More specifically：
Step 1：Compound such as formula 3 dissolves in ethanol, uses zinc powder/ammonium formate system to carry out catalytic hydrogenation, reaction
Temperature is 78 DEG C；
Step 2：After reduzate obtained by step 1, ester group is sloughed using methanol/sodium methoxide solution, after reaction terminates
Extracted with ethyl acetate, after post processing, obtain ursodeoxycholic acid crude；
Step 3：The ursodeoxycholic acid crude that step 2 obtains refines in ethanol water, obtains the ursodeoxycholic of sterling
Acid.
It is preferred that：
The solvent of step 1 is ethanol, and rate of charge n=1: 1.2: 1.2 (compound of formula 3: zinc powder: ammonium formate), reaction are warm
Spend for 78 DEG C, reaction time 15mn.
Organic solvent described in step 2 is methanol, and sodium methoxide need to dissolve the first for being made into that concentration is 2mol/L in methyl alcohol
Sodium alkoxide/methanol solution, reaction temperature are 25 DEG C, and the reaction time is 2 hours.
Step 3 is crystallized using the ethanol water of 80% concentration.
Embodiment
The present invention is described further with reference to embodiment：
Embodiment 1
Ethanol 400mL, the compound 40.8g (0.1mol) of formula 3, zinc powder 7.8g are added in 800mL three-necked flask
(0.12mol), ammonium formate 7.6g (0.12mol), is heated to reflux, and after reacting 15min, question response is cooled to room temperature and filtered,
Then concentration and recovery ethanol, 200mL ethyl acetate extraction is added, organic phase is washed 3 times with saturated aqueous common salt 100mL, then is passed through
Cross dry, concentration ethyl acetate obtains the solid of white, i.e. the compound of target product formula 2, white foaming solid (38.8g,
95.1%).1H NMR(CDCl3, 400MHz)：δ(ppm)：3.85-3.83 (br, 1H), 3.67 (s, 3H), 3.51-3.44 (m,
1H), 2.39-2.32 (m, 1H), 2.26-2.16 (m, 2H), 2.01-1.62 (m, 9H), 1.54-1.26 (m, 13H), 1.23-
1.11 (m, 3H), 1.02-0.98 (m, 1H), 0.93 (s, 3H), 0.90 (d, J=6.4Hz, 3H), 0.67 (s, 3H).
Embodiment 2
The compound of formula 2 (38.8g, 95.6mmol) is dissolved in 2mol/L sodium methoxide/methanol solution (200mL), in room temperature
Stirring stops reaction after 3 hours.Add the water extraction of 200mL ethyl acetate and 200mL, organic phase saturated aqueous common salt
100mL is washed 3 times, and solvent is removed in drying, concentration ethyl acetate rotation, obtains the compound of formula 1, white foaming solid
(37.1g, 99%).The ethanol water recrystallization of 80% concentration is reused, obtains White crystal powder, fusing point：203-204 DEG C,1H
NMR(CDCl3, 400MHz)：δ(ppm)：3.87-3.84 (br, 1H), 3.51-3.43 (m, 1H), 2.39-2.32 (m, 1H),
2.26-2.16 (m, 2H), 2.01-1.62 (m, 9H), 1.54-1.26 (m, 13H), 1.23-1.11 (m, 3H), 1.02-0.98 (m,
1H), 0.93 (s, 3H), 0.91 (d, J=6.4Hz, 3H), 0.66 (s, 3H).
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (4)
1. a kind of preparation method of urso, it comprises the following steps：
Step 1：The compound of formula 3 carries out catalytic hydrogenation using zinc powder/ammonium formate system and obtains the compound of formula 2；
Step 2：The compound of formula 2 sloughs ester group, obtains the ursodeoxycholic acid crude of formula 1；
Step 3：The ursodeoxycholic acid crude for the formula 1 that step 2 obtains is recrystallized to give the urso of sterling.
2. a kind of preparation method of urso according to claim 1, the wherein compound in step 1 such as formula 3 are molten
Solution carries out catalytic hydrogenation in ethanol, using zinc powder/ammonium formate system, reaction temperature is 78 DEG C.
3. a kind of preparation method of urso according to claim 2, wherein step 2 are by obtained by step 1
The compound of reduzate formula 2, ester group is sloughed using methanol/sodium methoxide solution, reaction is extracted after terminating with ethyl acetate, after
After processing, ursodeoxycholic acid crude is obtained.
4. the preparation method of any urso according to claim 1-3, it is characterised in that will step in step 3
Rapid 2 obtained ursodeoxycholic acid crudes 1 refine in ethanol water, obtain the urso of sterling.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610768367.7A CN107793464A (en) | 2016-08-30 | 2016-08-30 | A kind of preparation method of urso |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610768367.7A CN107793464A (en) | 2016-08-30 | 2016-08-30 | A kind of preparation method of urso |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107793464A true CN107793464A (en) | 2018-03-13 |
Family
ID=61528336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610768367.7A Pending CN107793464A (en) | 2016-08-30 | 2016-08-30 | A kind of preparation method of urso |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107793464A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319560A (en) * | 2013-01-04 | 2013-09-25 | 华东理工大学 | Preparation method of ursodeoxycholic acid |
| CN105418714A (en) * | 2015-12-28 | 2016-03-23 | 成都市新功生物科技有限公司 | Method for synthesizing ursodesoxycholic acid with chenodeoxycholic acid by photochemical method |
-
2016
- 2016-08-30 CN CN201610768367.7A patent/CN107793464A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319560A (en) * | 2013-01-04 | 2013-09-25 | 华东理工大学 | Preparation method of ursodeoxycholic acid |
| CN105418714A (en) * | 2015-12-28 | 2016-03-23 | 成都市新功生物科技有限公司 | Method for synthesizing ursodesoxycholic acid with chenodeoxycholic acid by photochemical method |
Non-Patent Citations (1)
| Title |
|---|
| CHEN GANG ET AL.: "Reduction of Aromatic α-Keto Esters by Commercially Available Zinc Dust and Ammonium Formate:Formation of Aromatic α-Hydroxy Esters", 《CHEM.RES.CHINESE UNIVERSITIES》 * |
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Application publication date: 20180313 |
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