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

Abstract

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 (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.

Putting precision and elegance in enzyme immobilisation with bio-orthogonal chemistry

“…However, some enzymes such as P450 monooxygenases 11 and ω-transaminase, 39 exhibited reduced activities (less than 50% of the free enzymes) which may have resulted from aggregation of enzymes in the internal pores of EZiG™ and hidden active sites inaccessible for substrates.…”

Biocatalyzed Redox Processes Employing Green Reaction Media

“…An attractive approach towards sustainable biocatalytic processes is to carry out enzymatic reactions directly in the substrate(s) without the addition of any solvent, since high productivity, competitiveness and reduced waste can be achieved [ 12 ]. There are several solvent-free systems including redox enzymes described in literature, using either whole-cells or isolated biocatalysts [ 34 , 35 , 36 , 37 ]. In all these examples, both the immobilization of isolated enzymes and/or the addition of a small amount of water (‘structural water’) were required to maintain the activity and flexibility of the biocatalysts.…”