An enzymatic synthesis process of Amoxicillin

A technology of amoxicillin and enzymatic synthesis, which is applied in the field of drug synthesis, can solve the problems of difficult screening and evaluation of immobilized enzymes, cumbersome production process steps, and long reaction time, and achieve good clarity, shortened reaction time, and fast reaction time short time effect

Inactive Publication Date: 2015-08-12
AMICOGEN CHINA BIOPHARM CO LTD
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

[0005] Aiming at the problems such as difficult screening and evaluation of immobilized enzymes, cumbersome production process steps, poor control points, long reaction time and lo

Method used

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  • An enzymatic synthesis process of Amoxicillin
  • An enzymatic synthesis process of Amoxicillin
  • An enzymatic synthesis process of Amoxicillin

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Experimental program
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Effect test

Embodiment 1

[0035] In the reactor, 1300 u of immobilized amoxicillin synthase LK218 was added to 130 mL of deionized water, and the stirring was started. 0.06 mol of 6-APA and 0.0612 mol of D-p-hydroxyphenylglycine methyl ester were added. Sodium hydroxide was added to adjust the reaction pH to 6.3. The reaction temperature was maintained at 19-20°C. Reaction 55min. The reaction solution was separated from the immobilized amoxicillin synthase. The obtained product was dissolved by adjusting the pH value to 0.9-1.1 with hydrochloric acid, filtered, adjusted the pH value with sodium hydroxide and crystallized, and the final pH value was 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of amoxicillin is obtained.

Embodiment 2

[0037] In the reactor, 1300 u of immobilized amoxicillin synthase LK218 was added to 130 mL of deionized water, and the stirring was started. 0.06 mol of 6-APA and 0.0618 mol of D-p-hydroxyphenylglycine methyl ester hydrochloride were added. Sodium hydroxide was added to adjust the reaction pH to 6.3. The reaction temperature was maintained at 14-15°C. Reaction 65min. The reaction solution was separated from the immobilized amoxicillin synthase. The obtained product was dissolved by adjusting the pH value to 0.9-1.1 with hydrochloric acid, filtered, adjusted the pH value with sodium hydroxide and crystallized, and the final pH value was 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of amoxicillin is obtained.

Embodiment 3

[0039] In the reactor, 1300 u of immobilized amoxicillin synthase LK218 was added to 130 mL of deionized water, and the stirring was started. 0.06 mol of 6-APA and 0.0612 mol of D-p-hydroxyphenylglycine methyl ester were added. Sodium hydroxide was added to adjust the reaction pH to 6.3. The reaction temperature was maintained at 10-11°C. Reaction 70min. The reaction solution was separated from the immobilized amoxicillin synthase. The obtained product was dissolved by adjusting the pH value to 0.9-1.1 with hydrochloric acid, filtered, adjusted the pH value with sodium hydroxide and crystallized, and the final pH value was 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of amoxicillin is obtained.

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Abstract

The invention relates to a synthesis method of medicines, and particularly relates to screening of an immobilized Amoxicillin synthase and an enzymatic synthesis process of Amoxicillin. The process includes immobilizing by adoption of an amino epoxy type carrier to obtain an immobilized Amoxicillin enzyme LK218, adding the immobilized Amoxicillin enzyme LK218, 6-aminopenicilanic acid and a D-p-hydroxyphenylglycine derivative into water, stirring, mixing to obtain a mixture, adjusting the pH value of the mixture by utilization of a hydrochloric acid solution and a sodium hydroxide solution, controlling the temperature and reaction time of the mixture, and finishing the reaction until the residual concentration of the 6-APA is 0-2 mg/mL. Aiming at problems, namely difficult screening and evaluation of immobilized enzymes, tedious production steps, poor reference points, long reaction time, low conversion ratios, and the like, the immobilized Amoxicillin enzyme and the novel synthesis process of the Amoxicillin are provided.

Description

technical field [0001] The invention relates to a method for synthesizing medicines, in particular to screening of immobilized amoxicillin synthase and a process for enzymatically synthesizing amoxicillin. Background technique [0002] Amoxicillin, whose real name is amoxicillin, is one of the most commonly used broad-spectrum β-lactam antibiotics. It has a bacteriolytic effect and is mainly used to treat bacterial infections caused by susceptible microorganisms. Amoxicillin is convenient to take, has high safety, good curative effect, few adverse reactions and low price, and is favored by doctors and patients. Among antibiotics, amoxicillin leads the way in sales, accounting for about 50% of the world's total sales of penicillin antibiotics. [0003] Since the mid-1990s, the enzymatic synthesis of amoxicillin has become a research focus. Compared with chemical methods, enzymatic methods have obvious advantages in terms of environmental protection and cost. The process of...

Claims

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Application Information

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IPC IPC(8): C12P37/04C12N11/02
Inventor 林炳旺王玲罗文军杨申永刘庆文乔浩
Owner AMICOGEN CHINA BIOPHARM CO LTD
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