Trypsin-catalyzed asymmetric aldol reactions of isatins with cyclic ketones and the mechanistic insights on activity differences at theoretical level

The promiscuous activity of bovine trypsin was explored in asymmetric aldol reactions between isatins and cyclic ketones. Detailed screening on the conditions with model substrates allowed to provide better catalytic performance. Especially, addition of calcium ion, as a natural stabilizer of trypsin, could improve stereoselectivity although slight losing yield. Furthermore, acceptability of various substrates was examined, a greatly impact on the yield and stereoselectivity have been observed from the different sizes of cyclic ketones. Docking and dynamics simulations were utilized to reveal the possible molecular basis of these phenomena.