CN1132207A - Method for prepn. of dihydro arteannuin - Google Patents
Method for prepn. of dihydro arteannuin Download PDFInfo
- Publication number
- CN1132207A CN1132207A CN 95111573 CN95111573A CN1132207A CN 1132207 A CN1132207 A CN 1132207A CN 95111573 CN95111573 CN 95111573 CN 95111573 A CN95111573 A CN 95111573A CN 1132207 A CN1132207 A CN 1132207A
- Authority
- CN
- China
- Prior art keywords
- artemisinin
- described method
- additive
- dihydroartemisinin
- phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
- C07C50/32—Quinones containing groups having oxygen atoms singly bound to carbon atoms the quinoid structure being part of a condensed ring system having two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/24—Quinones containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/38—Quinones containing —CHO or non—quinoid keto groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
A process for preparing is characterized by artemisinine that is reduced into dihydroartemisinine by use of phase-transfer catalyst and replacing sodium boron hydrogen by potassium boron hydrogen. Its advantages include low cost and high safety.
Description
The present invention relates to organic synthesis, more specifically say, terpenoid---the method for reducing of Artemisinin.
(I R=H) is a kind of new antimalarial agent to Dihydroartemisinin.(I) can be made through a step or a few step reaction as intermediate have other very strong new antimalarial agents of antimalarial effect.For example: Artemether (II, R=CH
3), Artesunate (III, R=COCH
2CH
2COOH), arteether (IV, R=C
2H
5), the upright acid of ligusticum sinense oliver (V, R=CH
2C
6H
4COOH) etc.This shows that in the research of artemisine new antimalarial agent, compound (I) is a kind of key intermediate.
I R＝H II R＝CH
2 III R＝COCH
2CH
2COOH IV R＝C
2H
5 V R＝CH
2C
6H
4COOH(p)
Artemisinin
Domestic scientist adopts sodium borohydride (NaBH in reported first in 1979
4) make reductive agent with preparation Dihydroartemisinin (chemical journal, 37 (2), 129).Its main method be Artemisinin in methanol solution with NaBH
40～5 ℃ of reaction down, obtain the Dihydroartemisinin crude product, productive rate about 90%.This method is so far by chemist employing both at home and abroad (J.Med.chem.1987,30 2147～2150; 1988,31 645～650).Relevant this reaction system is not seen bigger improved report so far.Adopt NaBH
4Reduction not only costs an arm and a leg, and under situation about dealing with improperly, inflammable, explosive.In malaria, be difficult for preserving.In reaction and last handling process, temperature control is particularly important.Improper as temperature control, cause productive rate to descend, even have an accident.In view of using NaBH
4Remain in above weak point, so potassium boron hydrogen (KBH in the presence of phase-transfer catalyst, is adopted in the present invention's design
4) replace sodium borohydride and as reductive agent Artemisinin is reduced.It is low that the present invention has a cost, operational safety, advantage easily.
The present invention implements through the following steps.
Artemisinin uses the different lower alcohol of water content as solvent in the presence of phase-transfer catalyst, under stirring at normal temperature, adds potassium boron hydrogen and reacts, and generally adopts the thin-layer chromatography method for tracing, judges whether to react completely.Question response fully after, reactant poured into separates out solid in the water, cross filter solid, solid water repetitive scrubbing.Be drying to obtain thick product, productive rate can reach about 85%.
The phase-transfer catalyst that uses can have following a few class:
1. polyethylene glycols: routine diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol monoethyl ether, PEG 200, and PEG 400, PEG 800 etc.
2. quaternary ammonium salt: routine Et
4N
+Cl
-, Bu
4N
+Br
-, PhCH
2N
+Me
3Cl
-, C
16H
33N
+Me
3Cl
-Deng.
3. crown ether-like: routine hexaoxacyclooctadecane-6-6 etc.
In reaction system, can add/mixture of not doping or additive, additive can be Na
2HPO
4, NaH
2PO
4, NaHSO
4, NaCl etc.
The invention will be further described to adopt embodiment, but do not limit the present invention.
Embodiment 1
Artemisinin 10g diethylene glycol dimethyl ether (diglyme) 4,8g and methyl alcohol 300ml are mixed, stir down, add potassium boron hydrogen 6g, at room temperature, reaction promptly takes place, and follows the trail of with thin-layer chromatography, after question response is complete, reactant is poured in the cold water, separated out white solid, leach solid, the water thorough washing gets the thick product of 8.6g Dihydroartemisinin after the drying.M.P.114-7℃
Embodiment 2
Artemisinin 5g is dissolved in methyl alcohol 120ml, adds PEG 200 2.2g, stirs to add KBH down again
41.9 gram adds levigated then and contains 2 parts of crystal water SODIUM PHOSPHATE, MONOBASIC 0.83g, reacts under the high degree of agitation, judges with the thin-layer chromatography method for tracing whether to react completely, after question response was complete, treatment process was the same.
Embodiment 3
Artemisinin 5g is dissolved in ethanol 150ml, adds quaternary ammonium salt Et
4N
+Cl
-0.6g, stir fully mixed down.Add KBH
42.8g, add then and contain 2 parts of crystal water SODIUM PHOSPHATE, MONOBASIC 0.83g.The post-reaction treatment operation is the same.
Embodiment 4
Artemisinin 5g is dissolved in aqueous ethanol 120ml, adds hexaoxacyclooctadecane-6-60.4g, stirs down, adds KBH
40.96g.Post-reaction treatment is the same.
Embodiment 5
Artemisinin 5g is dissolved in aqueous ethanol 180ml, adds quaternary ammonium salt C
16H
33N
+Me
3Cl
-2.3g NaCl 0.4g stirs adding KBH down
43.8g.Post-reaction treatment is the same.
Embodiment 6
Artemisinin 10g is dissolved in aqueous methanol 200ml, adds PEG 400 1.4g, Na
2HPO
4With NaH
2PO
4Mixture (1: 7) 4g, stir down, add KBH
41.9g.Post-reaction treatment is the same.
Claims (5)
1. a method for preparing Dihydroartemisinin by Artemisinin is characterized in that this method adopts in the presence of phase-transfer catalyst, the mixture that can add a kind of additive or additive, add potassium boron hydrogen in the aqueous alcohol solutions of Artemisinin, normal temperature reaction down makes Dihydroartemisinin.
2. according to the described method of claim 1, it is characterized in that reductive agent is a potassium boron hydrogen.
3. according to the described method of claim 1, it is characterized in that phase-transfer catalyst is polyethylene glycols or quaternary ammonium salt or crown ether-like.
4. according to the described method of claim 1, it is characterized in that additive is a Sodium phosphate dibasic, SODIUM PHOSPHATE, MONOBASIC, sodium-chlor, S-WAT or their mixtures more than two or two.
5. according to the described method of claim 1, it is characterized in that the solvent that reacts is low-grade alkane alcohol or their aqueous alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111573 CN1132207A (en) | 1995-03-25 | 1995-03-25 | Method for prepn. of dihydro arteannuin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95111573 CN1132207A (en) | 1995-03-25 | 1995-03-25 | Method for prepn. of dihydro arteannuin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1132207A true CN1132207A (en) | 1996-10-02 |
Family
ID=5078848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 95111573 Pending CN1132207A (en) | 1995-03-25 | 1995-03-25 | Method for prepn. of dihydro arteannuin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1132207A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102304135A (en) * | 2010-07-10 | 2012-01-04 | 恩施济源药业科技开发有限公司 | Method for producing dihydroartemisinin |
| CN102304134A (en) * | 2010-07-10 | 2012-01-04 | 恩施济源药业科技开发有限公司 | Process method for extracting dihydroartemisinin from waste mother liquor in production of dihydroartemisinin |
| CN103214496A (en) * | 2013-03-15 | 2013-07-24 | 彭学东 | Simple and rapid preparation process of dihydroartemisinin |
| CN107793426A (en) * | 2016-08-30 | 2018-03-13 | 天津太平洋制药有限公司 | A kind of preparation method of dihydroartemisinine |
| CN110041343A (en) * | 2019-05-29 | 2019-07-23 | 张家港威胜生物医药有限公司 | A kind of method that single process prepares dihydroartemisinine bulk pharmaceutical chemicals |
| CN111499651A (en) * | 2019-01-30 | 2020-08-07 | 昆药集团股份有限公司 | Dihydroartemisinin Form A crystal Form and preparation method thereof |
-
1995
- 1995-03-25 CN CN 95111573 patent/CN1132207A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102304135A (en) * | 2010-07-10 | 2012-01-04 | 恩施济源药业科技开发有限公司 | Method for producing dihydroartemisinin |
| CN102304134A (en) * | 2010-07-10 | 2012-01-04 | 恩施济源药业科技开发有限公司 | Process method for extracting dihydroartemisinin from waste mother liquor in production of dihydroartemisinin |
| CN102304134B (en) * | 2010-07-10 | 2013-06-26 | 恩施济源药业科技开发有限公司 | Process method for extracting dihydroartemisinin from waste mother liquor in production of dihydroartemisinin |
| CN103214496A (en) * | 2013-03-15 | 2013-07-24 | 彭学东 | Simple and rapid preparation process of dihydroartemisinin |
| CN107793426A (en) * | 2016-08-30 | 2018-03-13 | 天津太平洋制药有限公司 | A kind of preparation method of dihydroartemisinine |
| CN111499651A (en) * | 2019-01-30 | 2020-08-07 | 昆药集团股份有限公司 | Dihydroartemisinin Form A crystal Form and preparation method thereof |
| CN110041343A (en) * | 2019-05-29 | 2019-07-23 | 张家港威胜生物医药有限公司 | A kind of method that single process prepares dihydroartemisinine bulk pharmaceutical chemicals |
| CN111499653A (en) * | 2019-05-29 | 2020-08-07 | 张家港威胜生物医药有限公司 | Method for preparing dihydroartemisinin raw material medicine by single flow |
| WO2020238294A1 (en) * | 2019-05-29 | 2020-12-03 | 张家港威胜生物医药有限公司 | Method for preparing dihydroartemisinin active pharmaceutical ingredient in single process |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |