Biocatalytic access to nonracemic γ-oxo esters via stereoselective reduction using ene-reductases. Issue 2 (27th October 2016)

• Record Type: Journal Article
• Authors: Turrini, Nikolaus G.; Cioc, Răzvan C.; van der Niet, Daan J. H.; Ruijter, Eelco; Orru, Romano V. A.; Hall, Mélanie; Faber, Kurt
• Is Part Of: Green chemistry. Volume 19:Issue 2(2017)
• Page Start: 511
• Page End: 518
• Publication Date: 2016-10-27
• Subjects: Environmental chemistry -- Industrial applications -- Periodicals; Environmental management -- Periodicals; 660
• DOI: 10.1039/c6gc02493a
• Languages: English
• ISSNs: 1463-9262

Abstract

Abstract : α, β-Unsaturated γ-keto esters were asymmetrically reduced by ene-reductases to yield versatile chiral intermediates in up to 99% ee. Abstract : The asymmetric bioreduction of α, β-unsaturated γ-keto esters using ene-reductases from the Old Yellow Enzyme family proceeds with excellent stereoselectivity and high conversion levels, covering a broad range of acyclic and cyclic derivatives. Various strategies were employed to provide access to both enantiomers, which are versatile precursors of bioactive molecules. The regioselectivity of hydride addition on di-activated alkenes was elucidated by isotopic labeling experiments and showed strong preference for the keto moiety as activating/binding group as opposed to the ester. Finally, chemoenzymatic synthesis of ( R )-2-(2-oxocyclohexyl)acetic acid was achieved in high ee on a preparative scale combining enzymatic reduction followed by ester hydrogenolysis.