Trypsin-catalyzed aldol reactions of isatins with ketones and the mechanism probe of substrate selectivity by molecular simulations

Bovine trypsin displays a promiscuous activity to catalyze aldol reactions between isatins and ketones for easy access to 3-hydroxyindolin-2-ones. Detailed optimizations on the reaction conditions afforded the products with good yields, this system, which was compatible with various isatins. However, gradually enlarging the structure of ketones led to a significant decrease in yields. Molecular simulations were utilized to reveal the possible source of substrate selectivity. These results may provide valuable information for organic synthesis catalyzed by hydrolases.