Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent

• Main Authors: Wesley Böhmer, Lucien Koenekoop, Timothée Simon, Francesco G. Mutti
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Molecules
• Subjects: biocatalysis; asymmetric catalysis; kinetic resolution; α-chiral amines; enzyme immobilization; EziG
• Online Access: https://www.mdpi.com/1420-3049/25/9/2140

Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (<i>ee</i>, up to >99%) for the desired products. The progress of the conversion and <i>ee</i> was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.