Continuous-Flow Synthesis of Spiroindole Derivatives Catalyzed by Amano Acylase in Micro-Packed-Bed Reactors

Herein, we report the synthesis of spiroindole dervatives from a variety of isatin compounds, catalyzed by enzymes within micro-packed-bed reactors. This innovative approach was conducted in a micro-packed-bed reactor that was filled with enzymes, which facilitated efficient catalysis and significantly reduced the reaction time compared to traditional methods. The methodology was robust and versatile, succesfully affording a broad spectrum of spiroindole dervatives, with over 26 examples achieved in good to excellent yields. The yields were consistently high, demonstrating the reliability of the process. Furthermore, the developed process is highly scalable, making it suitable for induetrial applications, and operates under environmentally friendly conditions, which is crucial for sustainable chemical manufacturing. This study presents a significant advancement in the field of enzymatic synthesis, offering a green and efficient alternative for the production of spiroindole derivatives.