CN103724391A - Mono-etherification synthesis method of ginsenoside M1 and tert-butyldimethylsilyl chloride - Google Patents
Mono-etherification synthesis method of ginsenoside M1 and tert-butyldimethylsilyl chloride Download PDFInfo
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- CN103724391A CN103724391A CN201310575862.2A CN201310575862A CN103724391A CN 103724391 A CN103724391 A CN 103724391A CN 201310575862 A CN201310575862 A CN 201310575862A CN 103724391 A CN103724391 A CN 103724391A
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Abstract
The invention relates to a mono-etherification synthesis method of ginsenoside M1 and tert-butyldimethylsilyl chloride. Ginsenoside M1 and 5 equivalent weight of tert-butyldimethylsilyl chloride have a mono-etherification reaction at the room temperature under the conditions that nitrogen protection is performed and triethylamine is taken as a solvent as well as a deacid reagent, the etherification reaction is performed on 6-hydroxy of M1 glycosido radical, and the yield is 98%.
Description
Technical field
The present invention relates to the chlorosilane protective reaction of ginsenoside M1, belong to Chemistry for Chinese Traditional Medicine field.
Background technology
That ginseng has is anti-ageing, anti-inflammatory, antianaphylaxis, hypoglycemic, repairing nerve damage and the effect such as protect the liver.Research in recent years shows, ginsenoside has antineoplastic action, and major part is all with Rg
3, Rh
1, Rh
2deng being main study subject.They show remarkable effect at aspects such as promoting apoptosis of tumor cells and tumour cell differentiation, and the ginsenoside of different structure there are differences aspect anti-tumor activity, and wherein diol type ginsenoside anti-tumor activity is obviously better than triol type ginsenoside.Along with going deep into of saponin(e pharmacokinetic, what find real performance antitumor action is that secondary metabolite Compound K in saponin(e animal body also claims ginsenoside M1, and ginsenoside Compound K belongs to protopanoxadiol type saponin(e.Research shows that the esterified derivative of ginsenoside Compound K has better anti-tumor activity.EM1 (mixture of the stearate of M1, cetylate and oleic acid ester) compares and has stronger anti-tumor activity with ginsenoside M1.But EM1 source is limited, is difficult to separation and purification.And the serial ginsenoside M1 derivative poorly water-soluble that utilizes chemical synthesising technology to obtain.Adopt the modes such as ester bond, ehter bond to introduce water-soluble good group to the modification base of M1, it is had concurrently fat-soluble and water-soluble, on the structural formula of ginsenoside M1, have six hydroxyls, thereby selective esterification and raising mono-esterification productive rate have very important researching value.
Chlorosilane protects-goes protection process to be widely used in the protective reaction of hydroxyl; with chlorosilane by No. 6 position hydroxyl protections the most active on the glycosyl of Compound K; again with acyl chlorides generation esterification; the impact on esterification position according to kinetics and group steric hindrance size; thereby optimized the selectivity of single-esterification; be easy to separating-purifying, improve esterification productive rate.
Summary of the invention
summary of the invention:
The TERT-BUTYL DIMETHYL CHLORO SILANE of ginsenoside M1 and 5 equivalents is in room temperature, nitrogen protection, and triethylamine had both been made solvent and has been done under the condition of acid-binding agent simultaneously monoetherization reaction occurs, and etherificate occurs on No. 6 position hydroxyls of ginsenoside M1 glycosyl, and productive rate is 98%.
Concrete synthetic method: stop in good gram of bottle at the 25mL that magnetic stirrer is housed; add 100 mg Compound K; the TERT-BUTYL DIMETHYL CHLORO SILANE of 5 times of equivalents; nitrogen protection, adds appropriate triethylamine to dissolve under ice-water bath, after reaction 10 min; rise to room temperature; TLC monitors reaction process, and 24h after completion of the reaction, adds saturated ammonium chloride solution stopped reaction.Through CH
2cl
2(3 * 10 mL) extraction, Brine washes organic phase, anhydrous Na
2sO
4dry, concentrated solvent.
Column chromatography purification process: silica gel amount, 6g; Moving phase, ethanol/methylene;
After gradient elution, obtaining Rf value is 9/34 (8%MeOH/CH
2cl
2) product 110 mg
Product is Off-white solid
Positively effect of the present invention is with chlorosilane ginsenoside M1(ginsenoside Compound K) glycosyl on the most active No. 6 position hydroxyl protections; again with acyl chlorides generation esterification; the impact on esterification position according to kinetics and group steric hindrance size; thereby optimized the selectivity of single-esterification; be easy to separating-purifying, improve esterification productive rate.
the monoether of experimental example 1 ginsenoside M1 and TERT-BUTYL DIMETHYL CHLORO SILANE is combined to
Instrument and reagent:
Instrument: Agilent 1260 LC high performance liquid chromatographs; Buddhist nun Koryo 550 type Fourier transform infrared spectrometer; RE52CS-1 Rotary Evaporators, Shanghai Yarong Biochemical Instrument Plant; SHZ-D (III) rotation ability of swimming vacuum pump, Gongyi City Ying Yu Yu Hua instrument plant; ETS-D4 heats magnetic stirring apparatus, German IKA company; BT 323S electronic balance, Beijing Sai Duolisi instrument system company limited; FH-203 ultraviolet analysis instrument for three purposed (UV), Industrial Co., Ltd. of upper Nereid section; KQ-50B ultrasonic cleaner, Kunshan Ultrasonic Instruments Co., Ltd.; Column chromatography silica gel (200-300 order), Mouping District, Yantai Kombi promise chemical reagent factory; Tlc silica gel (GF254), Mouping District, Yantai Kombi promise chemical reagent factory;
Reagent: TERT-BUTYL DIMETHYL CHLORO SILANE, A Faaisha Chemical Co., Ltd.; Triethylamine, Tianjin Ke Miou chemical reagent company limited; Methylene dichloride, Chemical Reagent Co., Ltd., Sinopharm Group; Anhydrous sodium sulphate, Tianjin Ke Miou chemical reagent company limited; Methyl alcohol, Tianjin Ke Miou chemical reagent company limited
Building-up process: stop in good gram of bottle at the 25mL that magnetic stirrer is housed; add 100 mg Compound K; the TERT-BUTYL DIMETHYL CHLORO SILANE of 5 times of equivalents; nitrogen protection, adds appropriate triethylamine to dissolve under ice-water bath, after reaction 10 min; rise to room temperature; TLC monitors reaction process, and 24h after completion of the reaction, adds saturated ammonium chloride solution stopped reaction.Through CH
2cl
2(3 * 10 mL) extraction, Brine washes organic phase, anhydrous Na
2sO
4dry, concentrated solvent.
Column chromatography purification process: silica gel amount, 6g; Moving phase, ethanol/methylene;
After gradient elution, obtaining Rf value is 9/34 (8%MeOH/CH
2cl
2) product 110 mg
Product is Off-white solid
Structural Identification: through infrared spectrometer, high performance liquid chromatograph, nuclear magnetic spectrogram authenticating compound structure is
Embodiment
the monoether of embodiment 1 ginsenoside M1 and TERT-BUTYL DIMETHYL CHLORO SILANE is combined to method
At the 25mL that magnetic stirrer is housed, stop in good gram of bottle; add 100 mg ginsenoside M1(ginsenoside Compound K); the TERT-BUTYL DIMETHYL CHLORO SILANE of 5 times of equivalents; nitrogen protection, adds appropriate triethylamine to dissolve under ice-water bath, after reaction 10 min; rise to room temperature; TLC monitors reaction process, and 24h after completion of the reaction, adds saturated ammonium chloride solution stopped reaction.Through CH
2cl
2(3 * 10 mL) extraction, Brine washes organic phase, anhydrous Na
2sO
4dry, concentrated solvent, the monoether that obtains ginsenoside M1 and TERT-BUTYL DIMETHYL CHLORO SILANE is combined to product.
Accompanying drawing explanation
Fig. 1 is the structural formula figure that ginsenoside M1 and TERT-BUTYL DIMETHYL CHLORO SILANE monoether are combined to product.
Claims (3)
- One kind to take ginsenoside M1 and TERT-BUTYL DIMETHYL CHLORO SILANE be the method for single etherification product of the synthetic ginsenoside M1 of raw material; reaction conditions is nitrogen protection, and triethylamine had both been made solvent and done acid-binding agent simultaneously, reinforced under ice-water bath; after rise to room temperature, stopped reaction after 24 hours.
- 2. according to claim 1, the step of aftertreatment is for to use saturated ammonium chloride solution stopped reaction, and uses rapidly dichloromethane extraction three times, and anhydrous sodium sulfate drying spends the night, and decompression is spin-dried for solvent, after post separation, obtains product.
- 3. according to claim 1, its etherification product structural formula is shown in Fig. 1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210205387A1 (en) * | 2018-05-25 | 2021-07-08 | Green Cross Wellbeing Corporation | Composition for promoting myogenesis, containing processed ginseng extract |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101880305A (en) * | 2010-06-23 | 2010-11-10 | 大连大学 | Preparation method of ginsenoside metabolin M1 fatty acid ester compound |
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2013
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101880305A (en) * | 2010-06-23 | 2010-11-10 | 大连大学 | Preparation method of ginsenoside metabolin M1 fatty acid ester compound |
Non-Patent Citations (2)
| Title |
|---|
| CHAOLI ZHANG, ET AL.: "Synthesis of Neu5Ac-a-C-galactopyranosyl-functionalized magnetic nanoparticles via click chemistry", 《TETRAHEDRON》 * |
| 毛多斌等: "葡萄糖及葡萄糖苷的生物催化选择性酯化研究进展", 《日用化学工业》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210205387A1 (en) * | 2018-05-25 | 2021-07-08 | Green Cross Wellbeing Corporation | Composition for promoting myogenesis, containing processed ginseng extract |
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Application publication date: 20140416 |