Synergetic enzymatic reactive crystallization of cefaclor catalyzed by PGA

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In the context of the severe global carbon emission crisis, green and sustainable enzymatic reactions are garnering widespread attention in the industry. However, these processes still face numerous challenges, such as limitations imposed by reaction equilibrium, product decomposition, and inhibition. Product removal via crystallization has the potential to address these issues. More importantly, crystal product properties can be directly manipulated during enzymatic reactive crystallization (ERC), such as polymorphic purity, size, and morphology in a single batch. In the synthesis of cefaclor catalyzed by penicillin G acylase (PGA), primary and secondary hydrolysis greatly limited the efficiency of the reaction. Thus, ERC was performed to combine the advantages of green enzymatic reactions and controllable direct crystallization. Initially, a supersaturated solution of the substrate was established, and cefaclor crystals were seeded to the enzymatic reaction system at a proper time. Subsequently, operating parameters were adjusted to facilitate selective crystallization of cefaclor. It is noteworthy that both immobilized and free enzymes were examined in our research. Ultimately, cefaclor crystals with purity exceeding 99% were obtained directly. The yield of cefaclor reached as high as 88%. It is believed that this method held significant promise for the green and efficient production of high-purity cefaclor and demonstrated considerable potential for application in more similar pharmaceutical scenarios.