Method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid by one-step enzymatic reaction

A technology of aminoadipic acid and cephalosporin, applied in the direction of fermentation, can solve the problems of difficult control of the process, insufficient yield, purity and cost of the two-step enzymatic method, and achieve mild, safe and fast reaction conditions, and eliminate waste liquid. The effect of pollution, simple equipment

Inactive Publication Date: 2014-02-05
HARBIN PHARMA GRP CO LTD GENERAL PHARMA FACTORY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the two-step enzymatic method solves the environmental pollution problem of the chemical method, the two-step enzymatic method is somewhat insufficient in terms of yield, purity and cost, and the process of the previous step GL-7-ACA is difficult to control
[0011] Although these methods are superior to the two-step enzymatic method for preparing 7-aminocephalosporanic acid by one-step enzymatic method, the efficiency of different enzymes is very different, and its specific treatment method will also have an impact on the yield and purity of the product. , and does not involve the recovery and treatment of α-aminoadipic acid, the present invention finds a method that combines the chemical method (high yield and high purity) and the two-step enzymatic method ( The advantages of environmental protection and high yield), and at the same time, a simple and efficient method for recovering α-aminoadipic acid is provided, which is simpler than the 7-ACA obtained by the existing one-step enzymatic method, and the product yield is higher and the purity is higher High, the reaction conditions are milder and faster, and the discharged wastewater has almost no pollution, which not only saves production costs, protects the environment, but also creates new benefits

Method used

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  • Method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid by one-step enzymatic reaction
  • Method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid by one-step enzymatic reaction
  • Method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid by one-step enzymatic reaction

Examples

Experimental program
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Effect test

Embodiment 1

[0057] Take 10 liters of cephalosporin C (CPC) fermentation filtrate (750mM, equivalent to 311 grams of pure CPC), filter through a 1μm membrane, and adjust the pH to 10 with ammonia water.

Embodiment 2

[0058] Embodiment 2 reaction conditions control:

[0059] Add (NRB-103) enzyme 1800g to the reactor, wash twice with water, add CPC solution, under rapid stirring, control pH to 8-10 with ammonia water, react for 30 minutes, 7-ACA conversion rate is 98%.

Embodiment 3

[0060] The processing of embodiment 3 lysate (7-ACA liquid):

[0061] To the resulting 15 liters of 7-ACA solution was added 100 g of Na 2 S 2 o 4 , adjust the pH to 7 with ammonia water, add Tween 80, 10 ml, add 2000 ml of dichloromethane, stir for 10 minutes, separate phases, add 20 grams of activated carbon to the water phase, add 10 grams of EDTA, stir for 15 minutes, filter to remove carbon 7-ACA treatment solution was obtained.

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Abstract

The invention relates to a method for preparing 7-ACA (aminocephalosporanic acid) and obtaining alpha-aminoadipic acid. The method comprises the following steps of (1) treating cephalosporin C fermentation liquid; (2) performing an enzymolysis reaction of cephalosporin C under the effect of cephalosporin C acyltransferase to obtain 7-ACA; (3) treating the 7-ACA lysate after the enzymolysis; (4) separating out the 7-ACA; (5) separating alpha-aminoadipic acid from the separated 7-ACA lysate.

Description

Technical field: [0001] The invention relates to the application of an enzymatic cleavage method, in particular to a one-step enzymatic application for preparing 7-aminocephalosporanic acid and obtaining alpha-aminoadipic acid. Background technique: [0002] 7-aminocephalosporanic acid (7-aminocephalosporanic acid, 7-ACA), [0003] Structural formula: [0004] It is an important basic raw material for semi-synthetic cephalosporins. At present, cephalosporin C (Cephalosporin C, CPC) is usually cleaved by chemical method or two-step enzymatic method in industry to remove the 7-position D-α-aminohexadiene Acyl side chains give 7-ACA. [0005] α-Aminoadipic acid [0006] α-Aminoadipic acid (α-Aminoadipic acid), molecular weight 161.16, molecular formula C6H11N1O4, white crystal or white crystalline powder. It was first found in corn seeds or in the urine of humans and guinea pigs. Belonging to a kind of amino acid, it is widely used in medicine, food and feed, cosmetics i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P35/06C12P35/02C12P13/04
Inventor 朱彦民王喜军刘治林
Owner HARBIN PHARMA GRP CO LTD GENERAL PHARMA FACTORY
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