Recent advances in imine reductase-catalyzed reactions

Abstract

Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric reduction of various imines to the corresponding amine products. Owing to the increasing roles of chiral amines and heterocyclic compounds as intermediates for pharmaceuticals, the demand for novel selective synthesis strategies is vitally important. Recent studies have demonstrated the discovery and structural characterization of a number of stereoselective imine reductase enzymes. Here, we highlight recent progress in applying imine reductases for the formation of chiral amines and heterocycles. It particularly focuses on the utilization of imine reductases in reductive aminations of aldehydes and ketones with various amine nucleophiles, one of the most powerful reactions in the synthesis of chiral amines. Second, we report on the synthesis of saturated substituted N-heterocycles by combining them with further biocatalysts, such as carboxylic acid reductases, oxidases or transaminases. Finally, we summarize the latest applications of imine reductases in the promiscuous asymmetric hydrogenation of a highly reactive carbonyl compound and the engineering of the cofactor specificity from NADPH to NADH.

The identification and use of robust transaminases from a domestic drain metagenome

“…These factors mean, that as well as offering the advantages attributed to biocatalysis,4 biocatalytic aminations in particular are significantly more sustainable than their chemical counterpart. A number of different enzymes catalyse the formation of chiral amines, including transaminases (TAms),5,6 monoamine oxidases,7 imine reductases,8,9 lipases10 and amine dehydrogenases 11,12…”

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

“…Due to their high biological potential, N ‐heterocyclic β‐amino acids are important motifs in pharmaceutical and organic chemistry . A number of fluorine‐containing acyclic α‐ and β‐amino acids exhibit antitumoral or antibiotic properties . Biomolecules containing β‐fluorinated or β‐trifluorinated amine moieties are remarkable scaffolds in medicinal chemistry or agrochemistry .…”

Artificial imine reductases: developments and future directions

“…Biocatalysis remains an attractive target, capable of achieving high chemo-, regio-and enantio-selectivities under milder conditions than those required for traditional organometallic catalysis. 1,2 The preparation of chiral amines is a highly desirable target for biocatalysis. The enantioselective reduction of imines represents one key pathway to achieving some of these intermediates/products.…”