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Coupling process for preparing intermediate of semi-synthetic Cephalosperin antibiotics from penicillin fermentation liquid

A penicillin fermentation and penicillin technology, applied in the field of coupling process, can solve the problems of reporting or application of semi-synthetic antibiotic intermediates, and achieve the effects of saving extraction agent, shortening process flow, and improving light transmittance

Inactive Publication Date: 2007-05-09
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these technologies have not been reported or applied in the field of production of semi-synthetic antibiotic intermediates

Method used

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  • Coupling process for preparing intermediate of semi-synthetic Cephalosperin antibiotics from penicillin fermentation liquid
  • Coupling process for preparing intermediate of semi-synthetic Cephalosperin antibiotics from penicillin fermentation liquid

Examples

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Effect test

Embodiment 1

[0054] Embodiment 1, using the coupling process provided by the present invention to realize the production of 6-APA from penicillin G fermentation broth

[0055] Under low temperature (8~10 ℃), penicillin fermentation filtrate (1) obtains penicillin G filtrate (2) 500ml (titer is 31225 active units) through drum filtration (A); Ethylene oxide-polypropylene oxide block copolymer (wherein polyethylene oxide accounts for 50% by weight of copolymer) and the butyl acetate of 300ml join in the penicillin G filtrate, adjust pH with 10% sulfuric acid Make the pH=2.65, mix evenly and centrifuge at low speed (2000rpm, 3 minutes), and form a stable liquid-liquid-liquid three-phase system (B). The upper phase is a clear organic phase (3) loaded with penicillin; the middle phase is a reddish-brown aqueous phase rich in copolymers, and the interface contains impurities; the lower phase is a light yellow aqueous phase. As shown in Figure 2(a) and Table 1. Separate each phase, carry the pe...

Embodiment 2

[0056] Embodiment 2, coupling process realizes the penicillin G fermentation broth to produce 6-APA

[0057] Under low temperature, the penicillin fermentation filtrate is filtered through an ultrafiltration membrane to obtain 300ml of penicillin G filtrate (titer is 24512 active units); 100g of ammonium sulfate, 140g of polyethylene glycol, 5ml of isopropanol and 140ml of butyl acetate are mixed under stirring conditions Add it to the penicillin G filtrate, adjust the pH with 10% sulfuric acid to make the pH = 2.56, mix uniformly and let it settle for 10 minutes to form a stable liquid-liquid-liquid three-phase system. The upper phase is a clear organic phase loaded with penicillin; the middle phase is a reddish-brown aqueous phase rich in copolymers, and the interface is clear and free of impurities; the lower phase is a light yellow aqueous phase. Figure 2(b). Each phase is separated, and the butyl acetate organic phase loaded with penicillin is back-extracted with 7% pota...

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Abstract

The invention relates to a coupling process for preparing intermediate of semi-synthetic Cephalosperin antibiotics from penicillin fermentation liquid, which comprises the following five steps of fermentation liquor filtering, liquid-liquid-liquid extracting, inversed extracting, gas aid solvent extracting and hydrolyzing. The disclosed process can integrate the procedures of abstraction and impurity separation, and improve selectivity of the destination product.

Description

technical field [0001] The invention belongs to the technical field of antibiotic production, in particular to a production of hemizygous antibiotic intermediates such as 6-aminopenicillanic acid (6-APA) or 7-deacetylcephalosporanic acid (7- ADCA) coupling process. Background technique [0002] Penicillin is an important β-lactam antibiotic, and it is also the drug of choice for clinical antibacterial. The long-term use of penicillin in large quantities has led to the development of bacterial resistance. In order to solve these problems, new hemisynthetic penicillins have been continuously developed recently, and the demand is increasing. [0003] 6-APA and 7-ADCA are important intermediate raw materials for the production of hemisynthetic antibodies of β-lactams. At present, the traditional penicillin semi-synthesis technology is generally used in production. First, the fermentation liquid fermented by the strain is made into penicillin G potassium salt or sodium salt sol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D499/21C07D499/10C07D499/18C07D501/18C07D501/02
Inventor 申淑锋常志东刘会洲孙兴华安振涛胡欣刘吉
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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