Preparation method of 6-aminopenicillanic acid

A technology of aminopenicillic acid and penicillin acylase, which is applied in the field of biomedicine, can solve problems such as difficulty in environmental protection, and achieve the effects of improving production efficiency and improving catalytic efficiency.

Inactive Publication Date: 2016-05-11
QINGDAO MUNICIPAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

On the other hand, it produces high-concentration organic wastewater that is environmentally friendly and difficult to treat
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Method used

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  • Preparation method of 6-aminopenicillanic acid
  • Preparation method of 6-aminopenicillanic acid
  • Preparation method of 6-aminopenicillanic acid

Examples

Experimental program
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Embodiment 1

[0029] Example 1: Preparation of 6-APA

[0030] Place 1,000 mL of penicillin fermentation broth with a concentration of 100,000 U / mL in a stirred reactor with a temperature of 30-34° C. and stir. When the temperature of the fermentation broth reaches 30~34℃, add 60g of penicillin acylase (enzyme activity 120U / g) and 5mg of penicillin acylase activator as shown in the following structure for lysis, and continue to drip during the lysis process Ammonia water with a concentration of 10% maintains the pH value in the reactor at about 7.6. When the pH value in the reactor remains unchanged within 20 minutes after stopping the addition of ammonia water, the reaction ends.

[0031] The mixed liquid after the lysis reaction is passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is passed through an ultrafilter with a molecular weight cutoff of 30,000 to 50,000 Daltons and an ultrafilter with a molecular weight cutoff of 3000 t...

Embodiment 2

[0038] Example 2: Preparation of 6-APA

[0039] Place 1000 mL of penicillin fermentation broth with a concentration of 100,000 U / mL in a stirred reactor with a temperature controlled at 26-30°C and stir. When the temperature of the fermentation broth reaches 26~30℃, add 60g of penicillin acylase (enzyme activity 120U / g) and 5mg of penicillin acylase activator for lysis, and continuously add 10% concentration during the lysis process Ammonia water, the pH value in the reactor is maintained at 7.0-7.6, when the pH value in the reactor remains unchanged within 20 minutes after the addition of ammonia water is stopped, the reaction ends.

[0040] The mixed liquid after the lysis reaction is passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is passed through an ultrafilter with a molecular weight cutoff of 30,000 to 50,000 Daltons and an ultrafilter with a molecular weight cutoff of 3000 to 5000 Daltons to remove impuriti...

Embodiment 3

[0045] Example 3: Preparation of 6-APA

[0046] Place 1,000 mL of the penicillin fermentation broth with a concentration of 100,000 U / mL in a stirred reactor whose temperature is controlled at 34-38°C and stir. When the temperature of the fermentation broth reaches 34~38℃, add 60g of penicillin acylase (enzyme activity 120U / g) and 5mg of penicillin acylase activator for lysis, and continuously add 10% concentration during the lysis process Ammonia water, the pH value in the reactor is maintained at 7.6-8.5, when the pH value in the reactor remains unchanged within 20 minutes after the addition of ammonia water is stopped, the reaction ends.

[0047] The mixed liquid after the lysis reaction is passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is passed through an ultrafilter with a molecular weight cutoff of 30,000 to 50,000 Daltons and an ultrafilter with a molecular weight cutoff of 3000 to 5000 Daltons to remove i...

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Abstract

The invention discloses a method for preparing 6-aminopenicillanic acid, a penicillin acylase activator and application thereof in preparing the 6-aminopenicillanic acid. The penicillin acylase activator is a compound with a novel structure separated from a dry mature fruit of citrus chirocarpus, the compound is first reported, has an effect for improving the transforming activity of the penicillin acylase and can be used for preparing the 6-aminopenicillanic acid. A test result shows that after the penicillin acylase activator is added, not only can the yield of the 6-aminopenicillanic acid (6-APA) be increased, but also the pyrolysis time can be remarkably shortened, and the production efficiency is three times of that when the penicillin acylase activator is not added; therefore, the penicillin acylase activator can remarkably improve the transforming activity of the penicillin acylase and has prominent substantive characteristics and remarkable progress compared to the prior art.

Description

Technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a preparation method of 6-aminopenicillanic acid, a penicillin acylase activator and its application in preparing 6-aminopenicillanic acid. Background technique [0002] 6-Aminopenicillanic acid (6-APA) is a white flaky crystal, which is an important intermediate for the synthesis of various semi-synthetic penicillins and has a wide range of uses. Using this as a raw material for chemical structure modification and attaching side chains of different structures can produce new semi-synthetic penicillins that are sensitive to penicillin-resistant bacteria and have a broader antibacterial spectrum, such as ampicillin, amoxicillin, and phenoxymethyl. Penicillin, and other semi-synthetic penicillins with a broader antibacterial spectrum. At present, the domestic annual output of 6-APA exceeds 30,000 tons. [0003] At present, the industrial removal of penicillin side chain and cleavag...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P37/06C12P7/40C07D499/42C07D471/14
CPCC07D471/14C07D499/42C12P7/40C12P37/06
Inventor 赵明亮
Owner QINGDAO MUNICIPAL HOSPITAL
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