Manipulating the Activity and Diastereoselectivity of ω-Transaminase for the Synthesis of Bulky Aminopiperidines with Contiguous Stereocenters

Chiral aminopiperidines with contiguous stereocenters are valuable pharmaceutical intermediates, yet their asymmetric syntheses remain challenging. In this study, two variants of ATA-412 termed M3a and M10 with high activity and diastereoselectivity toward bulky substrates were obtained by protein engineering, and M10 showed reversed diastereoselectivity toward the atogepant intermediate. Furthermore, M10 was applied to catalyze the asymmetric synthesis of bulky aminopiperidines with high diastereoselectivity, providing a green and economical strategy for accessing these pharmaceutically relevant compounds.