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过程工程学报 ›› 2020, Vol. 20 ›› Issue (6): 711-717.DOI: 10.12034/j.issn.1009-606X.219233

• 生化工程 • 上一篇    下一篇

青霉素发酵液直接氧化制备青霉素G亚砜反应条件优化

闫 峰, 张为革*   

  1. 沈阳药科大学制药工程学院,辽宁 沈阳 110016
  • 收稿日期:2019-06-12 修回日期:2019-10-14 出版日期:2020-06-22 发布日期:2020-06-19
  • 通讯作者: 张为革 zhangweige2000@sina.com

Optimization of reaction conditions for preparation of penicillin G sulfoxide by direct oxidation of penicillin fermentation broth

Feng YAN, Weige ZHANG*   

  1. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
  • Received:2019-06-12 Revised:2019-10-14 Online:2020-06-22 Published:2020-06-19

摘要: 以过氧乙酸为氧化剂,研究了青霉素发酵液直接氧化制备青霉素G亚砜的过程,考察了不同影响因素对青霉素G亚砜转化率的影响,分析了氧化后菌丝中青霉素残留,建立并优化了青霉素发酵液直接氧化工艺。结果表明,搅拌转速、反应温度、过氧乙酸投料量、过氧乙酸浓度等因素是青霉素G亚砜转化率的关键影响因素,其他因素对青霉素发酵液直接氧化过程影响较小。过氧乙酸直接氧化青霉素发酵液可释放出残留在菌丝体内的青霉素,相比氧化青霉素G钾盐的转化率更高。最佳氧化工艺条件为反应温度5~10℃,搅拌转速100 r/min,30 min匀速加入青霉素摩尔量1.3倍的高浓度过氧乙酸,继续搅拌反应10 min。青霉素G亚砜的转化率可达98.6%,比青霉素G钾盐为原料的转化率提高1.2%。

关键词: 青霉素, 发酵液, 青霉素G钾盐, 青霉素G亚砜, 氧化

Abstract: The process of direct oxidation of penicillin G sulfoxide with penicillin fermentation broth was studied with peroxyacetic acid as oxidant, and a series of experiments were conducted to investigate the effects of different influencing factors on the conversion rate of penicillin G sulfoxide. The residual penicillin in the mycelium after oxidation was analyzed. The direct oxidation process of penicillin fermentation broth was established and optimized. The results showed that the stirring speed, reaction temperature, peroxyacetic acid feeding dosage and peroxyacetic acid concentration were the key factors affecting the conversion rate of penicillin G sulfoxide, other factors had little effect on the process. Peroxyacetic acid directly oxidized the penicillin fermentation broth and released penicillin remaining in the mycelium. So its conversion rate was higher than the conversion of penicillin G potassium salt. The optimum oxidation process conditions were reaction temperature of 5~10℃, stirring speed of 100 r/min, adding a high concentration of peroxyacetic acid in a molar ratio of 1.3 times of penicillin at 30 minutes, stirring reaction for 10 minutes after adding peroxyacetic acid. The conversion rate of penicillin G sulfoxide reached 98.6%, and the conversion rate increased by 1.2% than that of penicillin G potassium salt.

Key words: penicillin, penicillin fermentation, penicillin G potassium salt, penicillin G sulfoxide, oxidation