Abstract
Synthesis of cephalothin from thienylacetic acid (TAA) and 7-aminocephalosporanic acid (7ACA) has been carried out in the presence of high concentrations of organic cosolvents (e.g., 50% N,N′dimethyl-formamide) and under a wide range of experimental conditions (pH, temperature, etc.) by using very active and highly stabilized derivatives of Penicillin G acylase. We have been able to find the compromising solutions under which: (a) synthetic yields were markedly increased compared to those obtained in fully aqueous medium, (b) derivatives preserved a good percentage of catalytic activity, (c) derivatives were quite stable, and (d) high concentrations of substrates could be used. Under optimal conditions, 50 mM solutions of 7ACA in the presence of a slight excess of TAA were converted to cephalothin with yields higher than 95% and final concentrations of product up to 20 g/L were obtained.
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Fernandez-Lafuente, R., Alvaro, G., Blanco, R.M. et al. Equilibrium controlled synthesis of cephalothin in water-cosolvent systems by stabilized penicillin G acylase. Appl Biochem Biotechnol 27, 277–290 (1991). https://doi.org/10.1007/BF02921542
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DOI: https://doi.org/10.1007/BF02921542