Enantio-Complementary Continuous-Flow Synthesis of 2-Aminobutane Using Covalently Immobilized Transaminases

Chiral amines are a common feature of many active pharmaceutical ingredients. The synthesis very small chiral is particularly challenging, even via biocatalytic routes, as the level discrimination between similarly sized R-groups must be exceptional, yet their creates attractive building blocks that may then used to prepare diverse compounds in further steps. Herein, one smallest amines, 2-aminobutane, using transaminases, being investigated. After screening panel mainly wild-type two candidates were identified: an (S)-selective transaminase from Halomonas elongata (HEwT) and precommercial (R)-selective Johnson Matthey (*RTA-X43). Notably, single strategic point mutation enhanced enantioselectivity HEwT 45 >99.5% ee. By covalently immobilizing these candidates, both enantiomers 2-aminobutane synthesized on multigram scale, feasibility isolation by distillation without need for any solvents other than water was demonstrated. atom economy process calculated 56% E-factors (including waste generated during enzyme expression immobilization) 55 48 (R)-2-aminobutane (S)-2-aminobutane, respectively.