Research on Chemical Intermediates

, Volume 39, Issue 8, pp 3911–3917 | Cite as

A scalable chemoenzymatic process for 7-amino-3-[Z-2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid (ATCA)

  • Chun Hui Gao
  • Cheng Guo Jia
  • Wei Li
  • Yue Zhang
  • Yi Feng Yu
Article
  • 112 Downloads

Abstract

An efficient chemoenzymatic process has been developed for preparation of 7-amino-3-[Z-2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid, featuring removal of para-methoxybenzyl by trichloroacetic acid and cleavage of phenylacetyl E-isomer by immobilized penicillin acylase enzyme. The E-isomer of 7-amino-3-[Z-2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylic acid could be easily decreased to less than 0.2 % by salt formation. Importantly, trichloroacetic acid and immobilized penicillin acylase enzyme could be recovered and reused. The enzyme reaction could be run in a flow reactor. Only two crystallizations are involved as the purification procedure in the six-step sequence.

Keywords

Cefditoren pivoxil ATCA Deprotection Trichloroacetic acid Immobilized penicillin acylase Process 

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Chun Hui Gao
    • 1
  • Cheng Guo Jia
    • 2
  • Wei Li
    • 2
  • Yue Zhang
    • 1
  • Yi Feng Yu
    • 1
  1. 1.School of Chemical EngineeringHebei University of Science and TechnologyShijiazhuangChina
  2. 2.Department of R&DBrant Pharmaceuticals Co., Ltd.Jinzhou, ShijiazhuangChina

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