CN102532238A - Preparation method for celastrol long-chain alcohol ester - Google Patents
Preparation method for celastrol long-chain alcohol ester Download PDFInfo
- Publication number
- CN102532238A CN102532238A CN2010105965648A CN201010596564A CN102532238A CN 102532238 A CN102532238 A CN 102532238A CN 2010105965648 A CN2010105965648 A CN 2010105965648A CN 201010596564 A CN201010596564 A CN 201010596564A CN 102532238 A CN102532238 A CN 102532238A
- Authority
- CN
- China
- Prior art keywords
- tripterine
- long
- preparation
- chain alcohol
- alcohol ester
- 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
- 0 CC(CC1)([C@@](C)(CC[C@]23C)C4[C@]1(C)CC[C@@](C)(CO)C4)C2=CC=C(*=C1O)C3=CC1=O Chemical compound CC(CC1)([C@@](C)(CC[C@]23C)C4[C@]1(C)CC[C@@](C)(CO)C4)C2=CC=C(*=C1O)C3=CC1=O 0.000 description 1
Abstract
The invention belongs to the technical field of medicines, and relates to a preparation method for celastrol long-chain alcohol ester. The method comprises the following steps of: dissolving a raw material, namely celastrol in an organic solvent, adding an acid bonding agent and halogenated hydrocarbon in turn, stirring in the solvent for reaction, finishing the reaction, adding water, extracting by using an organic solvent, and performing chromatographic separation on an organic phase by using a concentrating column to obtain the product, namely the celastrol long-chain alcohol ester. The preparation method has the advantages that: the solvent with low toxicity and high safety is adopted, reaction conditions are mild, the product yield is high, the product quality is good, and the preparation method is suitable for large-scale production. In a reaction formula, RX refers to saturated or unsaturated halogenated hydrocarbon with the carbon atom number of 10-20, and X refers to Cl, Br or I.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of preparation method of Tripterine long-chain alcohol ester.
Background technology
It is one of major ingredient in the Chinese medicine trypterygine that prior art discloses Tripterine; Have multiple pharmacologically actives such as anti-inflammatory, antitumor, anti-oxidant, antimycotic and immunomodulatory; But because Tripterine has shortcomings such as poorly water-soluble, toxic side effect are big; Therefore, limited its use clinically.Patent documentation report (CN 101311187A) is prepared into its long-chain alcohol ester with Tripterine, and the verivate that obtains has significant prostate gland target property than Tripterine, and antitumor, anti-inflammatory activity is improved.
The disclosed preparation method about Tripterine long-chain alcohol ester comprises both at home and abroad:
Chinese patent CN 101311187A: this method uses long-chain alcohol to be raw material, with Tripterine under the effect of dewatering agent (like NSC 57182 DCC), obtain Tripterine long-chain alcohol ester.The shortcoming of this method is that productive rate is lower, has only 43%～65% usually.
Wang Jia waits ［ herbal medicine by force; 2009,40 (2), 201-204 ］: this method uses long-chain alcohol to be raw material; With Tripterine under 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDCI) effect, obtain Tripterine long-chain alcohol ester through high temperature dehydration.The shortcoming of this method is that productive rate is lower, has only 24%～36% usually, and reaction conditions is comparatively harsh, is inappropriate for mass preparation.
Because the Tripterine expensive raw material price, therefore in the process of esterification, how fully improving its transformation efficiency seems very important.
Summary of the invention
The objective of the invention is to overcome the defective of prior art, the technical problem that exists in the preparation Tripterine long-chain alcohol ester to prior art is improved, and is specifically related to a kind of preparation method of new Tripterine long-chain alcohol ester.
The preparation method of Tripterine long-chain alcohol ester of the present invention adopts more gentle reaction conditions, makes it to be suitable for mass preparation; Adopt the long-chain halohydrocarbon to replace long-chain alcohol, raw material Tripterine transformation efficiency is increased substantially, bring up to 80%～90%, obviously save production cost by 24%～65% of bibliographical information.
Particularly, the preparation method of Tripterine long-chain alcohol ester of the present invention is characterized in that it comprises step:
The raw material Tripterine is dissolved in organic solvent, adds acid binding agent, halohydrocarbon successively, stirring reaction in solvent adds water after the end, use organic solvent extraction, and organic phase evaporating column chromatographic separation gets product Tripterine long-chain alcohol ester,
Wherein, RX is the saturated or unsaturated halohydrocarbon of C10～C20, X=Cl, Br, I.
Among the present invention, described organic solvent is selected from
N, NThe combination of-N, DMSO 99.8MIN., acetone, acetonitrile, chloroform, methylene dichloride, THF, dioxane or above solvent etc., preferred in the embodiments of the invention
N, N-N;
Among the present invention, described acid binding agent is selected from sodium hydrogencarbonate, saleratus, yellow soda ash, salt of wormwood, triethylamine, diisopropylethylamine, pyridine etc., preferred sodium hydrogencarbonate in the embodiments of the invention;
Among the present invention, the mol ratio of halohydrocarbon RX and Tripterine is 0.5:1～10:1, is preferably 1.1:1～1.5:1 in the embodiments of the invention.
The preparing method's of Tripterine long-chain alcohol ester of the present invention advantage is,
1) solvent low toxicity, the security adopted are good,
2) reaction conditions is gentle, and product yield is high,
3) good product quality is fit to scale operation.
Embodiment
Be described in detail embodiment of the present invention below in conjunction with technical scheme.
Embodiment 1: preparation Tripterine hexadecanol ester
Reaction formula:
Take by weighing the Tripterine of 225.3 mg (0.5 mmol), be dissolved in 5 mL
N, N-N.The halo n-hexadecane that adds 252 mg (3.0 mmol) sodium hydrogencarbonate, 0.6 mmol successively.Stir 24 h under the room temperature, in reaction solution, add deionized water 50 mL then, with ethyl acetate extraction (20 mL * 3).Organic layer merges, successively with water, 10% hypo solution and saturated common salt water washing.The dry evaporating column chromatography of organic layer, (1:5, V:V) wash-out promptly get the positive hexadecanol ester of Tripterine with ethyl acetate/petroleum ether.
X=Br, yield 81.3%; X=I, yield 91.0%.
The positive hexadecanol of Tripterine esterification structural confirmation data are following:
ESI
+-MS:?653.8?(100%),?675.5?(90%,?M+H
+)；
1H-NMR?(CDCl
3,?400?MHz):?δ?7.01?(d,?
J?=?6.7?Hz,?1H),?6.97?(s,?1H),?6.52?(s,?1H),?6.34?(d,?
J?=?7.1?Hz,?1H),?3.95?(dt,?
J?=?10.7,?6.7?Hz,?1H,?H-1′a),?3.82?(dt,?
J?=?11.1,?6.3?Hz,?1H,?H-1′b),?2.43?(d,?
J?=?15.9?Hz,?1H),?2.21?(s,?3H,?H-23),?1.58?(brm,?16H,?CH
2),?1.47?(s,?3H,?Me),?1.17?(s,?3H,?Me),?1.09?(s,?3H,?Me),?0.87?(t,?
J?=?6.7?Hz,?3H,?H-16′),?0.54?(s,?3H,?Me)；
13C-NMR(CDCl
3,?100?MHz):?δ?178.8,?178.3,?170.1,?164.7,?146.0,?134.2,?127.3,?119.5,?118.1,?117.1,?64.6,?45.0,?44.2,?42.9,?40.3,?39.4,?38.2,?36.3,?34.8,?33.5,?32.8,?31.9,?31.6,?30.8,?30.5,?29.8,?29.7,?29.6,?29.5,?29.4,?29.2,?28.6,?28.4,?26.1,?22.7,?21.6,?18.4,?14.1,?10.3。
Embodiment 2: preparation Tripterine stearyl alcohol ester
Take by weighing the Tripterine of 225.3 mg (0.5 mmol), be dissolved in 5 mL
N, N-N.The halo Octadecane that adds 252 mg (3.0 mmol) sodium hydrogencarbonate, 0.7 mmol successively.Stir 24 h under the room temperature, in reaction solution, add deionized water 50 mL then, with ethyl acetate extraction (20 mL * 3).Organic layer merges, successively with water, 10% hypo solution and saturated common salt water washing.The dry evaporating column chromatography of organic layer, (1:5, V:V) wash-out promptly get the positive stearyl alcohol ester of Tripterine with ethyl acetate/petroleum ether.Work as X=Br, yield 79.3%; X=I, yield 88.7%.
Embodiment 3: preparation Tripterine eicosanol ester
Take by weighing the Tripterine of 225.3 mg (0.5 mmol), be dissolved in 5 mL
N, N-N.The halo NSC 62789 that adds 252 mg (3.0 mmol) sodium hydrogencarbonate, 0.7 mmol successively.Stir 24 h under the room temperature, in reaction solution, add deionized water 50 mL then, with ethyl acetate extraction (20 mL * 3).Organic layer merges, successively with water, 10% hypo solution and saturated common salt water washing.The dry evaporating column chromatography of organic layer, (1:5, V:V) wash-out promptly get the positive eicosanol ester of Tripterine with ethyl acetate/petroleum ether.Work as X=Br, yield 82.4%; X=I, yield 93.2%.
Claims (7)
1. the preparation method of a Tripterine long-chain alcohol ester is characterized in that it comprises step:
By following reaction formula the raw material Tripterine is dissolved in organic solvent, adds acid binding agent, halohydrocarbon successively, stirring reaction in solvent adds water after the end, use organic solvent extraction, and organic phase evaporating column chromatographic separation gets product Tripterine long-chain alcohol ester,
Wherein, RX is the saturated or unsaturated halohydrocarbon of C10～C20, X=Cl, Br, I.
2. by the described method of claim 1, it is characterized in that described organic solvent is selected from
N, NThe combination of-N, DMSO 99.8MIN., acetone, acetonitrile, chloroform, methylene dichloride, THF, dioxane or above solvent.
3. by the described method of claim 1, it is characterized in that described organic solvent is
N, N-N.
4. by the described method of claim 1, it is characterized in that described acid binding agent is selected from sodium hydrogencarbonate, saleratus, yellow soda ash, salt of wormwood, triethylamine, diisopropylethylamine or pyridine.
5. by the described method of claim 1, it is characterized in that described acid binding agent is a sodium hydrogencarbonate.
6. by the described method of claim 1, it is characterized in that the mol ratio of described halohydrocarbon RX and Tripterine is 0.5:1～10:1.
7. by the described method of claim 1, it is characterized in that the mol ratio of described halohydrocarbon RX and Tripterine is 1.1:1～1.5:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105965648A CN102532238A (en) | 2010-12-20 | 2010-12-20 | Preparation method for celastrol long-chain alcohol ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105965648A CN102532238A (en) | 2010-12-20 | 2010-12-20 | Preparation method for celastrol long-chain alcohol ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102532238A true CN102532238A (en) | 2012-07-04 |
Family
ID=46340393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105965648A Pending CN102532238A (en) | 2010-12-20 | 2010-12-20 | Preparation method for celastrol long-chain alcohol ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102532238A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134586A (en) * | 2018-10-17 | 2019-01-04 | 聊城大学 | Tripterine derivate and its application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101311187A (en) * | 2007-05-24 | 2008-11-26 | 烟台靶点药物研究有限公司 | Tripterine derivate, preparation method and use thereof |
| US20090054438A1 (en) * | 2007-08-17 | 2009-02-26 | Burnham Institute For Medical Research | Compositions and methods for inhibiting growth and metastasis of melanoma |
-
2010
- 2010-12-20 CN CN2010105965648A patent/CN102532238A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101311187A (en) * | 2007-05-24 | 2008-11-26 | 烟台靶点药物研究有限公司 | Tripterine derivate, preparation method and use thereof |
| US20090054438A1 (en) * | 2007-08-17 | 2009-02-26 | Burnham Institute For Medical Research | Compositions and methods for inhibiting growth and metastasis of melanoma |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109134586A (en) * | 2018-10-17 | 2019-01-04 | 聊城大学 | Tripterine derivate and its application |
| CN109134586B (en) * | 2018-10-17 | 2021-02-09 | 聊城大学 | Tripterine derivative and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108503681B (en) | Betulic acid derivative and its synthetic method and application | |
| CN103709131A (en) | Quercetin derivatives and synthetic method thereof | |
| CN104095857A (en) | Application of diethylamine derivative of Cleistanine in preparation of anti-hepatic fibrosis medicines | |
| CN113735709A (en) | Cannabidiol-2-butyrate and application thereof | |
| EP2840088B1 (en) | Method for preparing 5,6,4'-trihydroxyflavone-7-0-d-glucuronic acid | |
| CN102816199B (en) | Preparation and detection method of abiraterone Acetate dimer compound | |
| CN108409602B (en) | Method for preparing α -aryl nitrile compound | |
| CN104130195B (en) | A kind of haptenic synthetic method of carbendazim | |
| CN105906614A (en) | Preparation method of olmesartan medoxomil | |
| CN102532238A (en) | Preparation method for celastrol long-chain alcohol ester | |
| CN101921305B (en) | Method for preparing ginsenoside metabolite M1 fatty acid monoester compound | |
| CN103374049B (en) | One prepares 5,6, the method for 4 '-trihydroxyflavone-7-0-D-glucuronic acid | |
| CN103360376A (en) | Method for preparing 17 beta-HSD1 inhibitor | |
| CN103058941A (en) | Rupestonic acid containing heterocyclic ester derivatives and preparation method and use thereof | |
| CN103896998B (en) | The preparation method of Gastrodin Intermediate and the synthetic method of Gastrodin | |
| CN103483255A (en) | Fluorinated isoquinoline compounds and preparation method thereof | |
| CN106316871B (en) | A kind of amino acid derivativges of chiral beta 2 and preparation method thereof | |
| CN106632351A (en) | Method for preparing 6-bromine imidazo [1,2-a]pyrazine-3-nonanoic acid-ethyl ester | |
| CN108424383B (en) | Preparation method of curcumin nicotinate | |
| CN106995428B (en) | A kind of synthetic method of 6H- benzo [C] benzopyrans compounds | |
| CN102516066B (en) | Ostopanic acid analog and Preparation method and use | |
| CN108329291B (en) | Synthesis method of ionic liquid catalyzed 9-anthrone lactone compound | |
| CN102058610A (en) | Application of triterpenoidsaponin compound to preparing antihypertensive drug | |
| CN105566422B (en) | The preparation method of Suo Feibuwei intermediate or derivatives thereof | |
| CN104926674A (en) | (Z)-3-dimethylamino-2-phenoxy-alpha, beta-unsaturated amide and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120704 |