title: Penicillin acylase-catalyzed synthesis ofN-bromoacetyl-7-aminocephalosporanic acid, the key intermediate for the production of cefathiamidine.
abstract: BACKGROUND
  Enzymatic approaches have become promising alternatives to chemical methods for the production of semi-synthetic β-lactam antibiotics. In this work, enzymatic synthesis ofN-bromoacetyl-7-aminocephalosporanic acid (N-bromoacetyl-7-ACA), the key intermediate for the production of cefathiamidine, was reported for the first time.
  
  
  RESULTS
  Of the immobilized penicillin acylases (PAs) tested, PGA-750 was the best biocatalyst. Optimization of the biocatalytic process was conducted. The optimal acyl donor, molar ratio of acyl donor to 7-ACA, pH, temperature, 7-ACA concentration, and enzyme dosage were methyl bromoacetate, 3, 7.5, 20 °C, 50 mmol/L and 4 U/mL, respectively. Under the optimal conditions, enzymaticN-acylation of 7-ACA with methyl bromoacetate afforded the desired product with the yield of 85% in 2 h, where the synthesis/hydrolysis (S/H) ratio was approximately 1.5. The immobilized enzyme PGA-750 exhibited good operational stability, and the relative yields of approximately 90% and 63% were achieved, respectively, when it was reused in 7th and 11th batch.
  
  
  CONCLUSIONS
  An enzymatic approach toN-bromoacetyl-7-ACA, the key intermediate for the industrial production of cefathiamidine, has been developed successfully in a fully aqueous medium. The present work may open up a novel opportunity for the production of cefathiamidine through a simple and green process.Graphical abstractEnzymatic synthesis ofN-bromoacetyl-7-ACA, the key intermediate for the production of cefathiamidine, was reported for the first time.
authors.affiliation: School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510640 China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510640 China.
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zong
authors.affiliation: School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510640 China.
authors.forename: Ning
authors.identifier: 0000-0003-1684-4454
authors.initials: N
authors.lastname: Li
keywords: 7-Aminocephalosporanic acid; Cephalosporins; Enzyme catalysis; Penicillin acylase; Semi-synthetic antibiotics