CN103601783A - Mono-etherification synthetic method of ginsenoside M1 and tert-butyldiphenylsilane - Google Patents
Mono-etherification synthetic method of ginsenoside M1 and tert-butyldiphenylsilane Download PDFInfo
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- CN103601783A CN103601783A CN201310573204.XA CN201310573204A CN103601783A CN 103601783 A CN103601783 A CN 103601783A CN 201310573204 A CN201310573204 A CN 201310573204A CN 103601783 A CN103601783 A CN 103601783A
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- ginsenoside
- tert
- etherification
- mono
- butyldiphenylsilane
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Abstract
The invention relates to a mono-etherification synthetic method of ginsenoside M1 and tert-butyldiphenylsilane. The mono-etherification synthetic method is characterized in that the ginsenoside M1 and five equivalent of tert-butyldiphenylsilane are subjected to mono-etherification reaction at a room temperature by using triethylamine as a solvent and an acid binding agent under the protection of nitrogen, and the etherification happens on a site-sixth hydroxy of M1 glycosido group, and the yield is 80%.
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 with M1 has stronger anti-tumor activity.But EM1 source is limited, is difficult to separation and purification.And the serial 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 ginsenoside M1; 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
The monoether that the present invention relates to ginsenoside M1 and tert-butyl diphenyl chlorosilane is combined to method.The tert-butyl diphenyl chlorosilane 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 M1 glycosyl, and productive rate is 80%.
Concrete building-up process: stop in good gram of bottle at the 25mL that magnetic stirrer is housed; add 50mg ginsenoside M1; nitrogen protection; appropriate triethylamine dissolves, and adds the tert-butyl diphenyl chlorosilane of 5 equivalents under ice-water bath, reacts after 10 min; rise to room temperature; TLC monitors reaction process, and 48 h after completion of the reaction, add 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, 5g; Moving phase, ethanol/methylene; After gradient elution, obtain product.
positively effect of the present invention iswith chlorosilane by No. 6 position hydroxyl protections the most active on the glycosyl of ginsenoside 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.
the monoether of experimental example 1 ginsenoside M1 and tert-butyl diphenyl chlorosilane is combined to
1 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; Industrial Co., Ltd. of FH-203 ultraviolet analysis instrument for three purposed (UV) ，Shang 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 diphenyl chlorosilane, 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
2 building-up processes: stop in good gram of bottle at the 25mL that magnetic stirrer is housed; add 50 mg Compound K;, nitrogen protection, appropriate triethylamine dissolves; the tert-butyl diphenyl chlorosilane that adds 5 equivalents under ice-water bath; react after 10 min, rise to room temperature, TLC monitors reaction process; 48 h after completion of the reaction, add 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, 5g; Moving phase, ethanol/methylene;
After gradient elution, obtain product 55mg
Structural Identification: through infrared spectrometer, high performance liquid chromatograph, nuclear magnetic spectrogram authenticating compound structure is shown in Fig. 1.
Embodiment
the monoether of embodiment 1 ginsenoside M1 and tert-butyl diphenyl chlorosilane is combined to
At the 25mL that magnetic stirrer is housed, stop in good gram of bottle, add 50mg ginsenoside
m1, nitrogen protection, appropriate triethylamine dissolves, and adds the tert-butyl diphenyl chlorosilane of 5 equivalents under ice-water bath, reacts after 10 min, rises to room temperature, and TLC monitors reaction process, and 48 h after completion of the reaction, add 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, 5g; Moving phase, ethanol/methylene; After gradient elution, obtain product.
Claims (4)
- One kind to take ginsenoside M1 and tert-butyl diphenyl chlorosilane be the method for single etherification product of the synthetic ginsenoside M1 of raw material.
- 2. 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 48 hours.
- 3. 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.
- 4. according to claim 1, its etherification product structural formula be for:。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310573204.XA CN103601783A (en) | 2013-11-18 | 2013-11-18 | Mono-etherification synthetic method of ginsenoside M1 and tert-butyldiphenylsilane |
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|---|---|---|---|
| CN201310573204.XA CN103601783A (en) | 2013-11-18 | 2013-11-18 | Mono-etherification synthetic method of ginsenoside M1 and tert-butyldiphenylsilane |
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| CN103601783A true CN103601783A (en) | 2014-02-26 |
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Citations (2)
| 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 |
| CN102898495A (en) * | 2012-11-12 | 2013-01-30 | 浙江神洲药业有限公司 | Method for preparing abiraterone acetate |
-
2013
- 2013-11-18 CN CN201310573204.XA patent/CN103601783A/en active Pending
Patent Citations (2)
| 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 |
| CN102898495A (en) * | 2012-11-12 | 2013-01-30 | 浙江神洲药业有限公司 | Method for preparing abiraterone acetate |
Non-Patent Citations (1)
| Title |
|---|
| 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》, vol. 34, no. 6, 31 December 2004 (2004-12-31), pages 370 - 373 * |
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Application publication date: 20140226 |