Asymmetric Reductive Amination of Ketones Catalyzed by Imine Reductases. Issue 12 (19th May 2016)

• Record Type: Journal Article
• Authors: Wetzl, Dennis; Gand, Martin; Ross, Alfred; Müller, Hubertus; Matzel, Philipp; Hanlon, Steven P.; Müller, Michael; Wirz, Beat; Höhne, Matthias; Iding, Hans
• Is Part Of: ChemCatChem. Volume 8:Issue 12(2016)
• Page Start: 2023
• Page End: 2026
• Publication Date: 2016-05-19
• Subjects: amines -- asymmetric synthesis -- biocatalysis -- imine reductase -- reductive amination; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201600384
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: Biocatalysis employing imine reductases is a promising approach for the one‐step generation of chiral amines from ketones. The enzymes reported for this process suffer from low activity and moderate stereoselectivity. We identified a set of enzymes that facilitate this reaction with high to quantitative conversions from a library of 28 imine reductases. This enabled the conversion of ketones with ammonia, methylamine, or butylamine into the corresponding amines. Most importantly, we performed preparative (>100 mg) scale syntheses of amines such as (1 S, 3 R )‐ N, 3‐dimethylcyclohexylamine and ( R )‐ N ‐methyl‐2‐aminohexane with excellent stereochemical purities (98 % de, 96 % ee ) in good yields. Abstract : Matching pairs : Imine reductases can form chiral amines by direct reductive amination from ketones. We investigate this reaction by screening a library of 28 imine reductases to identify suitable enzymes. The identified imine reductases are applied in the preparation of chiral amines at ketone concentrations up to 1 % w/v with excellent conversions (>95 %) and stereoselectivities (>94 % ee or de ).