Asymmetric Ketone Reduction by Imine Reductases.
Maike Lenz1, Jan Meisner2, Leann Quertinmont3
1Institute of Technical Biochemistry, Universitaet Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Chembiochem : a European Journal of Chemical Biology
|December 3, 2016
Summary
Imine reductases (IREDs) now offer new ways to create chiral amines through stereoselective reduction. This study expands their use to trifluoroacetophenone, reducing both imine and carbonyl bonds.
Area of Science:
- Biocatalysis and enzyme engineering
- Organic synthesis
- Medicinal chemistry
Background:
- Chiral amines are crucial building blocks in pharmaceuticals and agrochemicals.
- Imine reductases (IREDs) are enzymes that catalyze the asymmetric reduction of imines to chiral amines.
- Expanding the substrate scope and catalytic capabilities of IREDs is essential for broader synthetic applications.
Purpose of the Study:
- To expand the substrate scope of imine reductases (IREDs) to include fluorinated ketones.
- To investigate the stereoselective reduction of both imine (C=N) and carbonyl (C=O) bonds using IREDs.
- To explore the influence of substrate reactivity on the chemoselectivity of IRED-catalyzed reactions.
Main Methods:
- In silico analysis of energy barriers to guide enzyme selection and reaction optimization.
- Asymmetric hydrogenation reactions using engineered imine reductases.
- Substrate screening including 2,2,2-trifluoroacetophenone and related imines and ketones.
Main Results:
- Demonstrated the stereoselective reduction of 2,2,2-trifluoroacetophenone, a challenging fluorinated substrate, by IREDs.
- Achieved asymmetric reduction of both imine (C=N) and carbonyl (C=O) bonds within the same molecule using IREDs.
- In silico analysis correlated with experimental results, providing insights into enzyme selectivity and reactivity.
Conclusions:
- Imine reductases exhibit a broader substrate scope and catalytic versatility than previously recognized.
- IREDs can be employed for the asymmetric synthesis of valuable chiral amines from fluorinated precursors.
- This work provides a foundation for the development of novel biocatalytic routes to complex chiral molecules.
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