Engineered Biocatalysts for Enantioselective Reductive Aminations of Cyclic Secondary Amines

Reductive aminases (RedAms) have recently emerged as promising biocatalysts for the synthesis of chiral secondary amines by coupling primary with aldehydes/ketones. However, access to tertiary remains more problematic, particularly when ketones amines. Here we show that scope these enzymes can be extended allow selective reductive aminations cyclic amines, such piperidines and morpholines, both aldehydes ketones. These biotransformations provide important motifs found in active pharmaceutical ingredients other bioactive molecules. RedAm-361, discovered from a metagenomic library, was engineered via directed evolution efficient carbonyl partners, including dynamic kinetic resolutions α-functionalized enantioselective amination RedAms now serve valuable scaffolds engineering industrial produce key intermediates.