Determination of lumped kinetic parameters and their thermal dependence for the synthesis of cephalexin with immobilized penicillin acylase in organic medium

The kinetically controlled synthesis of β-lactam antibiotics with penicillin acylase is favored at low temperatures and high cosolvent concentrations. The synthesis of cephalexin from 7-amino 3-desacetoxy cephalosporanic acid and phenylglycine methyl ester has been performed at varying temperatures below 20 °C with glyoxyl agarose-immobilized penicillin acylase in ethylene glycol medium at previously optimized pH, cosolvent concentration and nucleophile to acyl donor ratio. An equation for batch reactor performance was derived considering the kinetic mechanism proposed for the kinetically controlled synthesis of β-lactam antibiotics. From the experimental data gathered at different temperatures and the model of batch reactor performance developed, lumped kinetic parameters were determined at each temperature by a numerical method and temperature explicit polynomial functions for each kinetic parameter were derived.