Promiscuous acylase as a green catalyst: to directly catalyze the conjugate addition reaction for the synthesis of brivaracetam intermediates

Abstract

Epilepsy, a predominant neurological disorder affecting about 1% of the worldwide population, demands effective treatment options. An antiepileptic drug called brivaracetam has proven amazing efficacy in preventing epilepsy progression, garnering attention for novel synthesis methods. Despite recent progress in conventional synthesis routes, challenges such as expensive catalysts, inconvenient substrates, and hazardous solvents persist. In this context, we share the first finding that immobilized penicillin G acylase (IPGA) can catalyze the polarity reversal conjugate addition reaction. This synthesis is straightforward and does not require any purification. Yield up to 92.41% was achieved at 55 °C using dimethyl sulfoxide as a solvent. The catalytic specificity of IPGA was demonstrated through control experiments. Nonetheless, this research demonstrates the potential of IPGA and other biocatalysts to enable sustainable and effective organic synthesis processes and showcase the promiscuity of existing enzymes.

Graphical abstract