Method for catalyzing and synthesizing S-acetyl-L-glutathione from mixed solvent

A technology of glutathione and synthetic methods, which is applied in the preparation methods of peptides, chemical instruments and methods, peptides, etc., can solve the difficulty of selective acylation of sulfhydryl groups, acetyl-CoA is not easy to obtain, and is not suitable for large-scale industrial production, etc. problem, to achieve the effect of high purity and high yield

Inactive Publication Date: 2014-11-19
UNIV OF JINAN
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Since amino groups are easier to acylate than thiols, selective acylation of thiols is difficult, and few methods are known to date for the selective acylation of glutathione sulfhydryls without involving free amino groups, however, these methods exist Various disadvantages and not suitable for mass production
In 1954, W. Wayne Kielley and Louise B. Bradley used the exchange reaction between acetyl-CoA and GSH to produce S-acetyl glutathione (J. Biol. Chem. 1954, 206: 327-333), because acetyl-CoA A is not easy to obtain, and the above-mentioned enzymatic method is only suitable for laboratory-scale preparation, not suitable for large-scale industrial production

Method used

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  • Method for catalyzing and synthesizing S-acetyl-L-glutathione from mixed solvent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add glutathione 50g (0.16mol), 106mg AlCl 3 , 200mL of trifluoroacetic acid and 200mL of DMF, stir well, then raise the temperature to 40°C, add 13.8g (0.176mol) of acetyl chloride dropwise while stirring, take 10min, keep warm for 15min, TLC detects that there is no raw material point, drop 1.0g Methanol was incubated at 40°C for 15 minutes, and the solvent was recovered under reduced pressure after the reaction. Add 900mL of acetone / water (2:1) mixed solution to it and stir to dissolve. After dissolving, add triethylamine dropwise to adjust the pH to about 3. Add 300mL of acetone dropwise under slow stirring, let stand for crystallization for 1 hour after dropping, slowly cool down to 0°C, crystallize for 3 hours, filter with suction, rinse the filter cake with about 50-100mL of solvent and dry it at 70°C, that is S-acetyl-L-glutathione product 50.1g was obtained, the product yield was 89.5%, and the purity of the product detected by HPLC was greater than 99.3%.

Embodiment 2

[0024] Add 50g (0.16mol) of glutathione, 200mL of trifluoroacetic acid and 200mL of DMF into a 1 L three-necked flask equipped with a reflux condenser, a thermometer, and a mechanical stirrer, stir evenly, raise the temperature to 40°C, and add acetyl chloride dropwise while stirring 13.8g (0.176mol), it took 10min, and the temperature was kept for 15 minutes after dripping. TLC detected that there was no raw material point, and 1.0 g of methanol was added dropwise, and the reaction was kept for 15 minutes at 40°C. After the reaction, the solvent was recovered under reduced pressure. Add 900mL of acetone / water (2:1) mixed solution to it and stir to dissolve. After dissolution, triethylamine was added dropwise to adjust the pH to about 3. Add 300mL of acetone dropwise under slow stirring, let stand for crystallization for 1 hour after dropping, slowly cool down to 0°C, crystallize for 3 hours, filter with suction, rinse the filter cake with about 50-100mL of solvent and dry it ...

Embodiment 3

[0026] Add 50 g (0.16 mol) of glutathione, ZnCl 2 108mg, add 400mL trifluoroacetic acid, stir evenly, raise the temperature to 35°C, add 17.6 g (0.224mol) of acetyl chloride dropwise while stirring, take 10 minutes, keep warm for 20 minutes after dropping, TLC detects that there is no raw material point, drop 5.9g Ethanol was incubated at 35°C for 15 minutes, and the solvent was recovered under reduced pressure after the reaction. Add 900mL of acetone / water (2:1) mixed solution to it and stir to dissolve. After dissolving, trimethylamine was added to adjust the pH to about 3. Add 400mL of acetone dropwise under slow stirring, let stand for crystallization for 1 hour after dropping, slowly cool down to 0°C, crystallize for 3 hours, filter with suction, rinse the filter cake with about 50-100mL of solvent and dry it at 70°C, that is Obtain S-acetyl-L-glutathione product 48g, product yield 85.7%, HPLC detection product purity is greater than 99.3%.

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Abstract

The invention discloses a new method for catalyzing and synthesizing S-acetyl-L-glutathione (S-GSH) from a mixed solvent. According to the method, amidogen of strong acidic trifluoroacetic acid and L-glutathione (GSH) are adopted to salify in an aprotic polar solvent, so that the activity of the amidogen can be reduced; sulfydryl and an acylating agent acetyl chloride catalyze and synthesize the S-GSH from the mixed solvent; DMF and generated hydrogen chloride form DMF complex to play a role of an acid-binding agent, so that a sulfydryl acylation reaction can be conducted completely; alcohol is added to decompose excess acyl chloride and a non-water system is guaranteed, so that the trifluoroacetic acid can be recycled and reused. Calculated by the GSH, the yield of the S-GSH reaches 90% and the purity of the S-GSH is higher than 99.3%.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a method for synthesizing S-acetyl-L-glutathione. Background technique [0002] L-glutathione (γ-glutamyl-cysteinyl-glycine, GSH), a tripeptide containing SH, is the most important small molecule sulfhydryl compound in cells and an important water-soluble reducing agent in cells and detoxifiers. When the oxidant damages the protein in the body, glutathione is oxidized to glutathione disulfide through self-SH to protect the protein in the cell. However, due to the influence of free radicals and oxidants in the body, GSH decays rapidly in plasma. In addition, GSH cannot be directly absorbed by cells, and needs to be broken down into amino acids, and GSH is re-synthesized in cells. This process is often destroyed by bacterial infection. This obstacle can be overcome by a new derivative of GSH, S-acetyl-L-glutathione (S-GSH). S-GSH can not only exist stably in plasma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/037C07K1/107
Inventor 郑庚修付凯王秋芬杨柳马小芬陈环宇
Owner UNIV OF JINAN
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