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Synthesis process for preparing eslicarbazepine with microbial method

A technology of biotransformation and biocatalyst, which is applied in the field of heterocyclic chemistry and microbiology, can solve the problems of low conversion rate of raw materials, high toxicity of reagents, and many reaction steps, etc., and achieve the effect of high molar conversion rate, low cost and easy operation

Active Publication Date: 2014-11-26
瑞博(杭州)医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0029] The purpose of the present invention is to overcome the disadvantages of the above-mentioned prior art that the reaction reagent is highly toxic, the reaction steps are many, the separation is difficult, and the conversion rate of raw materials is low, and a new synthetic method for preparing eslicarbazepine acetate is provided.

Method used

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  • Synthesis process for preparing eslicarbazepine with microbial method
  • Synthesis process for preparing eslicarbazepine with microbial method
  • Synthesis process for preparing eslicarbazepine with microbial method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Slant culture: Inoculate CGMCC No.2230 bacteria into the slant medium and culture at 30°C for 4-6 days. The slant medium is prepared as follows: wort juice 10g / L, yeast powder 3g / L, peptone 5g / L, glucose 10g / L, agar 20g / L, natural pH, solvent is water; sterilized at 121°C 20min, after sterilizing, cool to make a slope.

[0055] Seed culture and fermentation: Both the seed and the fermentation medium use liquid medium, which is prepared according to the following composition: glucose 30g / L, yeast powder 3g / L, ammonium sulfate 5g / L, anhydrous MgSO 4 0.25g / L, K 2 HPO 4 ·3H 2 O 1g / L, KH 2 PO 4 1g / L, sterilized at 121°C for 20min. Adjust the pH of the liquid medium to 7.0 with NaOH or HCl solution.

[0056] Use an inoculation needle to take an inoculation loop of bacteria from the slant medium and inoculate it into a 250ml Erlenmeyer flask containing 100ml of liquid medium, and culture it at 30°C and 180r / min for 24 hours to obtain a seed solution. The seed solutio...

Embodiment 2

[0061] Slant culture: Inoculate CGMCC No.2230 bacteria into the slant medium and culture at 30°C for 4-6 days. The slant medium is prepared as follows: wort juice 10g / L, yeast powder 3g / L, peptone 5g / L, glucose 10g / L, agar 20g / L, natural pH, solvent is water; sterilized at 121°C 20min, after sterilizing, cool to make a slope.

[0062] Seed culture and fermentation: Both the seed and the fermentation medium use liquid medium, which is prepared according to the following composition: glucose 30g / L, yeast powder 3g / L, ammonium sulfate 5g / L, anhydrous MgSO 4 0.25g / L, K 2 HPO 4 ·3H 2 O 1g / L, KH 2 PO 4 1g / L, sterilized at 121°C for 20min. Adjust the pH of the liquid medium to 7.0 with NaOH or HCl solution.

[0063] Use an inoculation needle to take an inoculation loop of bacteria from the slant medium and inoculate it into a 250ml Erlenmeyer flask containing 100ml of liquid medium, and culture it at 30°C and 180r / min for 24 hours to obtain a seed solution. The seed solutio...

Embodiment 3

[0068] Slant culture: Inoculate CGMCC No.2230 bacteria into the slant medium and culture at 30°C for 4-6 days. The slant medium is prepared as follows: wort juice 10g / L, yeast powder 3g / L, peptone 5g / L, glucose 10g / L, agar 20g / L, natural pH, solvent is water; sterilized at 121°C 20min, after sterilizing, cool to make a slope.

[0069] Seed culture and fermentation: Both the seed and the fermentation medium use liquid medium, which is prepared according to the following composition: glucose 30g / L, yeast powder 3g / L, ammonium sulfate 5g / L, anhydrous MgSO 4 0.25g / L, K 2 HPO 4 ·3H 2 O 1g / L, KH 2 PO 4 1g / L, sterilized at 121°C for 20min. Adjust the pH of the liquid medium to 7.0.

[0070]Use an inoculation needle to take an inoculation loop of bacteria from the slant medium and inoculate it into a 250ml Erlenmeyer flask containing 100ml of liquid medium, and culture it at 30°C and 180r / min for 24 hours to obtain a seed solution. The seed solution was inoculated in a 250ml...

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Abstract

The invention relates to the technical fields of heterocyclic chemistry and microorganisms, in particular to a synthesis process for preparing eslicarbazepine with a microbial method. In view of the defects of high toxicity of all reagents, more reaction steps, difficulty in splitting, low raw material conversion rate and the like in the prior art, the invention provides a novel synthesis process for preparing eslicarbazepine acetate, wherein the eslicarbazepine is prepared through biotransformation reaction by taking oxcarbazepine as a substrate and an enzyme-containing thalli cell, obtained through fermenting saccharomyces cerevisiae CGMCC No.2230, as a biocatalyst.

Description

technical field [0001] The invention relates to the technical fields of heterocyclic chemistry and microorganisms, in particular to the technical field of preparation of a chiral compound and the application of microorganisms. Background technique [0002] Eslicarbazepine acetate (ESL, S-(-)-10-acetoxy-10, 11-dihydro-5H-dibenz / b, f / azepine-5-carboxamide), code name BIA 2-093, Also known as eslicarbazepine acetate, eslicarbazepine acetate molecular formula C 17 h 16 N 2 o 3 , molecular weight 296.32, CAS number: 236395-14-5, structural formula as follows: [0003] [0004] Eslicarbazepine acetate [0005] It is a new type of anti-epileptic drug, which can selectively inhibit the rapid discharge of nerve cells that cause epileptic seizures, and produces therapeutic effects by regulating the activity of sodium channels. It has good safety, especially low neuropsychiatric side effects. Not only can it significantly reduce the frequency of seizures in patients with refra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/12C12N1/16C12R1/865
Inventor 欧志敏沈文和车大庆
Owner 瑞博(杭州)医药科技有限公司
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