Gao, C.H., Jia, C.G., Li, W. et al. Res Chem Intermed (2013) 39: 3911. doi:10.1007/s11164-012-0907-0
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.