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Synthesis method of ergothioneine

A kind of technology of ergothioneine and synthetic method, applied in the field of ergothioneine synthesis, can solve the problems of high cost, low product yield, expensive reagents, etc., and achieve the effect of short synthetic route, high yield and efficient thiolation

Active Publication Date: 2022-04-29
GUANGZHOU JORBLE BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Extracting ergothioneine from animal tissues and edible fungi has low yield and high cost, which limits the application of ergothioneine
The biosynthesis of ergothioneine by the submerged fermentation technology of mushroom mycelium can effectively improve the yield of ergothioneine and reduce the production cost through metabolic regulation and other fermentation process control means, but the yield of the product obtained by this method is low
It is difficult to prepare ergothioneine by chemical synthesis, and the synthetic reagents are expensive, and the safety is difficult to be guaranteed

Method used

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  • Synthesis method of ergothioneine
  • Synthesis method of ergothioneine
  • Synthesis method of ergothioneine

Examples

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preparation example Construction

[0028] A kind of synthetic method of ergothioneine, comprises the following steps:

[0029] (1) Boc protection of histidine: dissolve histidine in the first solvent to obtain a histidine solution, add sodium hydroxide and di-tert-butyl dicarbonate in turn, and stir the reaction after adding di-tert-butyl dicarbonate , after the reaction is completed, adjust the pH to 3-5 with formic acid, add water to precipitate a solid, filter and dry to obtain Boc-protected histidine;

[0030] (2) One-pot thiolation: dissolve the Boc-protected histidine in the second solvent to obtain a Boc-protected histidine solution, add sodium bromide and iodobenzene acetate in turn, stir and react for 2-4 hours, and control the temperature Lower than 40°C, add sodium sulfide after the reaction is completed, raise the temperature to 70°C-100°C for 4-6 hours, after the reaction is completed, cool down to room temperature, add water, then add sulfuric acid to adjust the pH of the solution to 3-5, and prec...

Embodiment 1

[0043] A kind of synthetic method of ergothioneine, comprises the following steps:

[0044] (1) Dissolve histidine (1.55kg, 10mol, 1.0equiv) in 10L of tetrahydrofuran and water in a mixed solvent with a volume ratio of 1:1 at room temperature, and slowly add sodium hydroxide (0.4kg, 10mol, 1.0 equiv), then slowly add di-tert-butyl dicarbonate (2.18kg, 10mol, 1.0equiv), add and stir at room temperature for 10 hours, TLC shows that the reaction is complete, adjust the pH to 4 with formic acid, add 20L of water, and precipitate a large amount of solid , filtered and dried to obtain 2.32 kg of Boc-protected histidine with a yield of 91%.

[0045] (2) Dissolve Boc-protected histidine (1.27kg, 5mol, 1.0equiv) in 5L of acetonitrile and water in a mixed solvent with a volume ratio of 1:1 at room temperature, add sodium bromide (0.52kg, 5mol, 1.0equiv), then slowly add iodobenzene acetate (1.61kg, 5mol, 1.0equiv), and control the temperature below 40°C. After the addition was complet...

Embodiment 2

[0050] Same as Example 1, the difference is:

[0051] Step (4) Dissolve thiohistidine (9.3g, 150mM, 1.0equiv) in water at room temperature, slowly add 450mM S-adenosylmethionine (SAM), thiohistidine and S-adenosyl The molar ratio of glycoside methionine is 1:3, then add 0.58 mg EgtD (ergothioneine methyltransferase, derived from Mycobacterium smegmatis) to catalyze the trimethylation reaction of thiohistidine histidine, 37 °C React for 2 hours to generate ergothioneine. After the conversion is complete, use a Sephadex ged column to remove the enzyme. After the product is concentrated under reduced pressure, use a silica gel column to purify to obtain pure ergothioneine. Purified ergothioneine 0.84 g, yield 90.3%.

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Abstract

The invention discloses a synthesis method of ergothioneine. The synthesis method comprises the following steps: (1) dissolving histidine in a first solvent, adding sodium hydroxide and di-tert-butyl dicarbonate, then adjusting the pH value with formic acid, adding water to precipitate a solid, filtering and drying to obtain Boc-protected histidine; (2) dissolving Boc-protected histidine in a second solvent, adding sodium bromide and iodosobenzene diacetate for stirring reaction, adding sodium sulfide for reaction after reaction, adjusting the pH value of the solution, separating out a solid, filtering and drying to obtain sulfo-Boc histidine; (3) dissolving and stirring the thio-Boc histidine for reaction, decompressing and draining the solvent, dropwise adding the concentrated liquid into methyl tert-butyl ether for crystallization, and filtering and drying to obtain thio-histidine; and (4) methylation: performing methylation by a chemical catalysis or biological enzyme method to obtain purified ergothioneine. The synthesis method provided by the invention is short in synthesis route, high-efficiency thioation is realized by a one-pot method, and meanwhile, the yield of the obtained product ergothioneine is high.

Description

technical field [0001] The invention belongs to the technical field of compound synthesis, in particular to a method for synthesizing ergothioneine. Background technique [0002] Ergothioneine (mercaptohistidine trimethyl salt, ergothioneine, EGT) is a natural antioxidant discovered in 1909. It was originally found in a fungus, Claviceps purpurea. The pure product is a white crystal, water-soluble, ( It can dissolve 0.9mol / L at room temperature, and it will not oxidize itself at physiological pH and in strong alkaline solution. It can protect cells in the human body and is an important active substance in the body. Natural antioxidants are safe and non-toxic, and have become a research hotspot. As a natural antioxidant, ergothioneine has entered people's field of vision. It has many physiological functions such as scavenging free radicals, detoxifying, maintaining DNA biosynthesis, normal cell growth and cellular immunity. [0003] There are three kinds of preparation tec...

Claims

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Application Information

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IPC IPC(8): C07D263/46C12P17/10
CPCC07D263/46C12P17/10Y02P20/55
Inventor 马哲正郑涵鹿寿海
Owner GUANGZHOU JORBLE BIOTECH CO LTD
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