Article

Research on Chemical Intermediates

, Volume 39, Issue 8, pp 3911-3917

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

  • Chun Hui GaoAffiliated withSchool of Chemical Engineering, Hebei University of Science and Technology
  • , Cheng Guo JiaAffiliated withDepartment of R&D, Brant Pharmaceuticals Co., Ltd.
  • , Wei LiAffiliated withDepartment of R&D, Brant Pharmaceuticals Co., Ltd.
  • , Yue ZhangAffiliated withSchool of Chemical Engineering, Hebei University of Science and Technology Email author 
  • , Yi Feng YuAffiliated withSchool of Chemical Engineering, Hebei University of Science and Technology

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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