Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine

A glutamate dipeptide and process system technology are applied in the preparation field of enzyme catalyzed synthesis of glutamate dipeptide, can solve the problems of affecting the purity and quality of glutamate dipeptide, long reaction synthesis route, large environmental pollution, etc., and achieve high economic value and market competitiveness, low cost, Equipment requires simple effects

Active Publication Date: 2015-04-29
JIANGSU CHENGXIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] CN101659691A and CN1786019A disclose a kind of chemical synthesis and industrialized production method (the following route) of dipeptide, but the reaction synthesis route of this method is long, the environment pollution is big, and the process cost is high
[0007] In the existing follow-up process of enzymatic synthesis to prepare dipeptide, the crude product will be mixed with enzymes in the reaction solution, which is difficult to remove and affects the purity and quality of dipeptide

Method used

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  • Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine
  • Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine
  • Preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine

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Experimental program
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Embodiment 1

[0058]Add 180kg of methanol into the 1000L reactor and cool down to 0°C; add 78.6kg of thionyl chloride dropwise into the reactor at 0°C; add 52.5kg of L-alanine in one go Put it into the reaction kettle, keep it warm and stir for 30min, then slowly raise the temperature to 25°C, stir for 1h, then raise the temperature to 45°C and stir for 2h; evaporate most of the solvent at 50°C under reduced pressure to obtain 90kg of L-alanine methyl ester salt;

Embodiment 2

[0060] Add 180kg of methanol into a 1000L reactor and cool down to 10°C; add 78.6kg of thionyl chloride dropwise into the reactor at 10°C; add lysine to the reactor at one time after the addition of thionyl chloride is complete , keep stirring for 30 minutes, then slowly raise the temperature to 30°C, stir for 1h, then raise the temperature to 50°C and stir for 2h; evaporate most of the solvent at 50°C under reduced pressure to obtain 82L-alanine methyl ester salt;

Embodiment 3

[0062] Add 180kg of methanol into the 1000L reactor, and lower the temperature to 5°C; add 78.6kg of thionyl chloride dropwise into the reactor at 5°C; , keep stirring for 30 minutes, then slowly raise the temperature to 28°C, stir for 1h, then raise the temperature to 48°C and stir for 2h; evaporate most of the solvent at 50°C under reduced pressure to obtain 88kg of L-alanine methyl ester salt;

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Abstract

The invention provides a preparation method and technological system for enzymatically synthesizing N(2)-L-alanyl-L-glutamine. The preparation method comprises the steps of synthesis of L-alanine methyl ester, synthesis of N(2)-L-alanyl-L-glutamine, inactivation of enzymes, filtration, preparation of a crude product I of N(2)-L-alanyl-L-glutamine and preparation of a crude product II of N(2)-L-alanyl-L-glutamine. The technological system also comprises a production line formed by an L-alanine methyl ester synthesis kettle (1), an L-alanine methyl ester storage tank (2), an N(2)-L-alanyl-L-glutamine synthesis reaction kettle (3), an enzyme storage tank (4), a storage tank (5), a resin column (6) and mother liquor recovery tanks (7). The preparation method and the technological system have the technical effects that impurities are effectively removed, thus improving the purity of a finished product; the requirements for equipment are simple; the yield is high, after-treatment is simple to carry out, and the cost is low.

Description

technical field [0001] The invention relates to a method for synthesizing dipeptide, in particular to a method for synthesizing dipeptide with high-efficiency enzyme-catalyzed synthesis technology, in particular to a preparation method and a process system for dipeptide synthesized by enzymes. Background technique [0002] N (2) -L-alanyl-L-glutamine (also known as alanyl glutamine) is a derivative of amino acid, referred to as proglutide, which is mainly used in the human health industry and is the most abundant amino acid in the human body An ideal substitute for glutamine. [0003] Due to the extremely important physiological functions and pharmacological effects of glutamine, its application in parenteral nutrition has received widespread attention. However, due to its low solubility and instability in solution, toxic pyroglutamic acid and ammonia are generated under heat sterilization conditions, so commercial amino acid preparations do not contain glutamine. Only by ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P21/02C12M1/00C07K5/062C07K1/36C07K1/34C07K1/30C07K1/22
Inventor 邢将军许刘华任世阔吴锋刘加根华俊国沈为标
Owner JIANGSU CHENGXIN PHARMA
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