Method for catalytically synthesizing s-acetyl-l-glutathione in mixed solvent

A technology of glutathione and synthesis method, which is applied to the preparation methods of peptides, chemical instruments and methods, peptides, etc., and can solve the problems of difficulty in selective acylation of sulfhydryl groups, difficult availability of acetyl-CoA, and unsuitability for large-scale production. , to achieve the effect of high yield and high purity

Inactive Publication Date: 2017-12-26
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 catalytically synthesizing s-acetyl-l-glutathione in mixed solvent
  • Method for catalytically synthesizing s-acetyl-l-glutathione in mixed solvent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 50 g (0.16 mol) of glutathione, 106 mg of 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, and take 10min. 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 takes 10min, after dripping, keep warm for 15min, TLC detects that there is no raw material point, drop 1.0g methanol, keep warm for 15min at 40°C, and recover the solvent under reduced pressure after the reaction. 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 at 70°C, that is S-acetyl-L-glutathione product 44g was obtained, the...

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, and take 10 minutes. 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 catalytically synthesizing S-acetyl-L-glutathione (S-GSH) in a mixed solvent. Using strongly acidic trifluoroacetic acid and the amino group of L-glutathione (GSH) to form a salt in an aprotic polar solvent, the activity of the amino group is reduced, and the mercapto group and the acylating agent acetyl chloride are used to catalyze the synthesis of S-GSH in a mixed solvent , DMF and the generated hydrogen chloride form a DMF complex, which acts as an acid-binding agent to complete the mercapto acylation reaction. After the reaction is completed, alcohol is added to decompose excess acid chloride to ensure an anhydrous system, so that the trifluoroacetic acid can be recycled and reused. In terms of GSH, the yield of S-GSH reaches 90%, and the purity is greater 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 Patents(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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