CN104072577A - Method for preparing S-acetyl-L-glutathione - Google Patents
Method for preparing S-acetyl-L-glutathione Download PDFInfo
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- CN104072577A CN104072577A CN201410310430.3A CN201410310430A CN104072577A CN 104072577 A CN104072577 A CN 104072577A CN 201410310430 A CN201410310430 A CN 201410310430A CN 104072577 A CN104072577 A CN 104072577A
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- preparation
- gsh
- acetyl
- reaction system
- chemical formula
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- 0 C*(*1)c2ccccc2*1C(C)=O Chemical compound C*(*1)c2ccccc2*1C(C)=O 0.000 description 1
- VYNPQJGCTBBHQG-UHFFFAOYSA-N CC(C1N=Nc2ccccc2CC1)=O Chemical compound CC(C1N=Nc2ccccc2CC1)=O VYNPQJGCTBBHQG-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention provides a relatively simple method for preparing S-acetyl-L-glutathione. A mixture of acetonitrile and water is used as a reaction system, the reaction system is regulated to be weakly acidic after reaction, and a product can be separated out by direct stirring. The method is very simple and convenient in operation and relatively high in yield, and can be used for effectively removing impurities from the product.
Description
Technical field
The preparation method who the present invention relates to compound S-acetyl-GSH, belongs to chemical field.
Background technology
GSH, molecular formula C
20h
32n
6o
12s
2, CAS 27025-41-8.GSH is made up of L-glutamic acid, halfcystine and glycine, can assist body immune system to keep normal function, and have anti-oxidant, integrate the effect such as removing toxic substances.GSH at present in the country such as U.S. as drug use, examination and approval procedures are comparatively strict.S-acetyl-GSH, chemical formula
molecular formula C
12h
19n
3o
7s, CAS 3054-47-5.Recent study is found, oral S-acetyl-GSH can improve the content of GSH in body, and S-acetyl-GSH is not yet only managed as foodstuff additive as medicine in a lot of countries, just day by day become the raw material of a kind of important protective foods or functional food.Some countries such as the U.S. are commercially available to be had in the protective foods of the function such as anti-oxidant and has added S-acetyl-GSH, and main attraction using S-acetyl-GSH as product.
Preparation S-acetyl-GSH is with benzotriazole (chemical formula
molecular formula C
6h
5o
3, CAS 95-14-7), Acetyl Chloride 98Min. (molecular formula C
2h
3clO, CAS 75-36-5), GSH etc. is raw material, with triethylamine (molecular formula C
6h
15n, CAS 121-44-8), saleratus etc. is the catalyzer of each step reaction.These compounds are all commercial chemical at present, can directly buy from Chemical market.
Traditional method of preparing S-acetyl-GSH is generally taking first alcohol and water as reaction system, first heating decompression steams methyl alcohol (this can destroy portion of product) after completion of the reaction, then by reaction system furnishing acidity, extraction, discard organic phase, water high-temperature pressure-reduction is concentrated, and then adds acetone, obtains solid product.Not only step is more for traditional method, complicated operation, and the yield of product is lower, and purity is not high.
The invention provides a kind of preparation method of comparatively simple S-acetyl-GSH, taking the mixture of acetonitrile and water as reaction system, after react, reaction system is adjusted to slightly acidic, directly stirring, can separate out product.This method operation is very easy, and yield is higher, and can effectively remove the impurity in product.
Summary of the invention
The invention provides a kind of preparation method of comparatively simple S-acetyl-GSH.
The preparation method of S-acetyl-GSH, comprises the following steps:
A chemical formula is
compound and Acetyl Chloride 98Min. carry out condensation reaction, generate chemical formula be
compound;
B chemical formula is
compound and GSH in the mixture of acetonitrile and water, carry out condensation reaction, after having reacted, reaction system is adjusted to slightly acidic, directly stir, can separate out chemical formula and be
compound.
As the optional embodiment of one, the condensation reaction in steps A is carried out in methylene dichloride, taking triethylamine as catalyzer.
The mixture of acetonitrile and water in step B, the volume ratio of acetonitrile and water is 1:1.
As the optional embodiment of one, in step B, reaction system is adjusted to slightly acidic and can uses hydrochloric acid, slightly acidic scope is pH value 4.0-5.0.
In step B, stir and separate out chemical formula and be
compound after, can in reaction system, add acetone or ethyl acetate, then stir.After adding acetone or ethyl acetate, stir again the amount of separating out that can increase compound.As the optional embodiment of one, identical with the volume of acetonitrile initial in reaction system or water to the volume of the acetone adding in reaction system or ethyl acetate.
In the present invention, the chemical formula of related all compounds all meets international chemical formulation rule: represent in functional group's sensing paper that interatomic singly-bound, use "=" represents that interatomic pair of key, use "----" represent to be connected with chiral carbon atom use with "-"
represent that the functional group being connected with chiral carbon atom points to outside paper; Homoatomic does not represent by atomic symbol but chemical bond between atomic symbol and the hydrocarbon atom of carbon atom, hydrogen atom omits (in the time that carbon atom or hydrogen atom and other atoms form functional group jointly, the atomic symbol of carbon atom or hydrogen atom retains).
The invention provides a kind of preparation method of comparatively simple S-acetyl-GSH.This method operation is very easy, and yield is higher, and can effectively remove the impurity in product.
Brief description of the drawings
Fig. 1 is the HNMR spectrogram of the light yellow solid that makes in embodiment 1.
Fig. 2 is the HNMR spectrogram of the white solid that makes in embodiment 2.
Fig. 3 is the LC-MS spectrogram of the white solid that makes in embodiment 2.
Fig. 4 is the HPLC spectrogram of the white solid that makes in embodiment 2.
Fig. 5 is the HPLC spectrogram of the white solid that makes in embodiment 3.
Fig. 6 is the HPLC spectrogram of the white solid that makes in embodiment 4.
Embodiment
Below will by embodiment, the present invention is described in detail, but content of the present invention is not limited to embodiment.
The synthetic route of S-acetyl-GSH is as follows:
Embodiment 1: preparing chemical formula is
compound
By benzotriazole (150g, 1.26mol), triethylamine (153g, 1.51mol) joins in 2L there-necked flask, adds 1L methylene dichloride to dissolve completely.Under 0 DEG C of stirring, drip the dichloromethane solution (107ml/107ml) of Acetyl Chloride 98Min., control temperature of reaction not higher than 2 DEG C, in 1 hour, dropwise, then under equality of temperature, stir 30 minutes.Pour above-mentioned reaction solution in frozen water (1L), wash again (1L*2) after separating organic layer, dry, concentrated, obtain light yellow solid 180g.As shown in Figure 1, HNMR spectrogram can confirm that the chemical formula of this light yellow solid is to nucleus magnetic resonance (HNMR) spectrogram of this light yellow solid
the yield of the present embodiment product is 74%.
Embodiment 2: preparation S-acetyl-GSH (directly stirring)
Get the light yellow solid (80g, 496mmol) making in embodiment 1, GSH (128g, 416mmol) joins in 1L round-bottomed flask, adds 304ml acetonitrile and 152ml water, stirs the lower 152ml of dropping KHCO
3the aqueous solution, dropwised in 30 minutes.Continue to stir 15 minutes, be then adjusted to PH4.0 with the hydrochloric acid of 1N, stir and within 1 hour, separate out solid, filter, acetonitrile washing, dry, obtain white solid 120g.As shown in Figure 2, as shown in Figure 3, HNMR spectrogram and LC-MS spectrogram can confirm that the chemical formula of this white solid is to mass spectrum (LC-MS) spectrogram to nucleus magnetic resonance (HNMR) spectrogram of this white solid
be that white solid is S-acetyl-GSH.As shown in Figure 4, HPLC spectrogram shows that the purity of S-acetyl-GSH is 96.0% to high performance liquid chromatography (HPLC) spectrogram of this white solid.The yield of the present embodiment S-acetyl-GSH is 83%.
Embodiment 3: preparation S-acetyl-GSH (stirring again after adding ethyl acetate)
Repeat embodiment 1.Get the light yellow solid (80g, 496mmol) making, GSH (128g, 416mmol) joins in 1L round-bottomed flask, adds 304ml acetonitrile and 152ml water, stirs the lower 152ml of dropping KHCO
3the aqueous solution, dropwised in 30 minutes.Continue to stir 15 minutes, be then adjusted to PH4.0 with the hydrochloric acid of 1N, stir and separate out solid in 1 hour, add ethyl acetate 304ml, continue to stir 1 hour, filter, acetonitrile washing, dry, obtain white solid 125g.High performance liquid chromatography (HPLC) spectrogram of this white solid as shown in Figure 5, the peak shape of this HPLC spectrogram main peak is almost identical with the HPLC spectrogram in embodiment 2 with peak position, can determine that the white solid that the present embodiment makes is also S-acetyl-GSH, the purity of S-acetyl-GSH is 96.4%.The yield of the present embodiment S-acetyl-GSH is 86%.
Embodiment 4: preparation S-acetyl-GSH (stirring again after adding acetone)
Repeat embodiment 1.Get the light yellow solid (80g, 496mmol) making, GSH (128g, 416mmol) joins in 1L round-bottomed flask, adds 304ml acetonitrile and 152ml water, stirs the lower 152ml of dropping KHCO
3the aqueous solution, dropwised in 30 minutes.Continue to stir 15 minutes, be then adjusted to PH4.0 with the hydrochloric acid of 1N, stir and separate out solid in 1 hour, add acetone 304ml, continue to stir 1 hour, filter, acetonitrile washing, dry, obtain white solid 130g.High performance liquid chromatography (HPLC) spectrogram of this white solid as shown in Figure 6, the peak shape of this HPLC spectrogram main peak is almost identical with the HPLC spectrogram in embodiment 2 with peak position, can determine that the white solid that the present embodiment makes is also S-acetyl-GSH, the purity of S-acetyl-GSH is 96.5%.The yield of the present embodiment S-acetyl-GSH is 90%.
Claims (6)
- The preparation method of 1.S-acetyl-GSH, is characterized in that, described preparation method comprises the following steps:A chemical formula is compound and Acetyl Chloride 98Min. carry out condensation reaction, generate chemical formula be compound;B chemical formula is compound and GSH in the mixture of acetonitrile and water, carry out condensation reaction, after having reacted, reaction system is adjusted to slightly acidic, directly stir, can separate out chemical formula and be compound.
- 2. preparation method according to claim 1, is characterized in that, the condensation reaction described in steps A is carried out in methylene dichloride, taking triethylamine as catalyzer.
- 3. preparation method according to claim 1, is characterized in that, the mixture of the acetonitrile described in step B and water, and the volume ratio of acetonitrile and water is 1:1.
- 4. preparation method according to claim 1, is characterized in that, reaction system is adjusted to slightly acidic and can uses hydrochloric acid described in step B, and slightly acidic scope is pH value 4.0-5.0.
- 5. preparation method according to claim 1, is characterized in that, the chemical formula stirring described in separating out in step B is compound after, can in reaction system, add acetone or ethyl acetate, then stir.
- 6. preparation method according to claim 5, is characterized in that, the volume of described acetone to adding in reaction system or ethyl acetate is identical with the volume of acetonitrile initial in reaction system or water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410310430.3A CN104072577A (en) | 2014-07-01 | 2014-07-01 | Method for preparing S-acetyl-L-glutathione |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410310430.3A CN104072577A (en) | 2014-07-01 | 2014-07-01 | Method for preparing S-acetyl-L-glutathione |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237489A (en) * | 2015-11-16 | 2016-01-13 | 上海应用技术学院 | Process for synthesizing N-caprylyl benzotriazole |
| CN114605491A (en) * | 2022-03-24 | 2022-06-10 | 安庆辰泰生物科技有限公司 | Preparation method of S-acetyl-L-glutathione and application of mixed solvent |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2760956A (en) * | 1954-03-31 | 1956-08-28 | Distillers Co Yeast Ltd | Production of s-acetyl glutathione |
| EP0536231A1 (en) * | 1990-06-26 | 1993-04-14 | Boehringer Mannheim Italia | A process for the preparation of glutathione s-acyl derivatives, compounds obtained from said process and an intermediate useful for the preparation thereof. |
| WO2009047728A2 (en) * | 2007-10-12 | 2009-04-16 | Università Degli Studi Di Firenze | New s-acyl-glutathione derivatives, their syntesis and use in the treatment of oxidative stress-related diseases |
| WO2013068964A1 (en) * | 2011-11-08 | 2013-05-16 | Solosale S.R.L. | Pharmaceutical composition for the prevention and the treatment of degenerative skin disorders especially caused by ionizing radiations |
-
2014
- 2014-07-01 CN CN201410310430.3A patent/CN104072577A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2760956A (en) * | 1954-03-31 | 1956-08-28 | Distillers Co Yeast Ltd | Production of s-acetyl glutathione |
| EP0536231A1 (en) * | 1990-06-26 | 1993-04-14 | Boehringer Mannheim Italia | A process for the preparation of glutathione s-acyl derivatives, compounds obtained from said process and an intermediate useful for the preparation thereof. |
| WO2009047728A2 (en) * | 2007-10-12 | 2009-04-16 | Università Degli Studi Di Firenze | New s-acyl-glutathione derivatives, their syntesis and use in the treatment of oxidative stress-related diseases |
| WO2013068964A1 (en) * | 2011-11-08 | 2013-05-16 | Solosale S.R.L. | Pharmaceutical composition for the prevention and the treatment of degenerative skin disorders especially caused by ionizing radiations |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237489A (en) * | 2015-11-16 | 2016-01-13 | 上海应用技术学院 | Process for synthesizing N-caprylyl benzotriazole |
| CN105237489B (en) * | 2015-11-16 | 2017-11-21 | 上海应用技术学院 | A kind of synthesis technique of N caprylyls BTA |
| CN114605491A (en) * | 2022-03-24 | 2022-06-10 | 安庆辰泰生物科技有限公司 | Preparation method of S-acetyl-L-glutathione and application of mixed solvent |
| CN114605491B (en) * | 2022-03-24 | 2024-02-06 | 安庆辰泰生物科技有限公司 | Preparation method of S-acetyl-L-glutathione and application of mixed solvent |
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Application publication date: 20141001 |