Shifting the equilibrium of a biocatalytic cascade synthesis to enantiopure epoxides using anion exchangers

Hydroxide-loaded anion exchangers have been successfully employed to shift the equilibrium of a one-pot, two-step, two-enzyme cascade reaction affording enantiopure epoxides starting from prochiral α-chloroketones. The α-chloroketones were asymmetrically reduced employing an alcohol dehydrogenase and then transformed further to the corresponding epoxides employing halohydrin dehalogenases. Each epoxide enantiomer could be obtained with up to 93% conversion in enantiomerically pure form (>99% ee). In contrast to previous studies the amount of hydride donor (2-propanol) could be reduced due to favoured halohydrin formation in the reduction of α-chloroketones.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(S)-1,2-Epoxy-3-phenoxypropaneC9H10O2Ee >99%[α]D20=+4.5 (c 1, CHCl3)Source of chirality: asymmetric synthesis (biotransformation)Absolute configuration: (S)

(R)-1,2-EpoxyoctaneC8H16OEe >99%[α]D20=+4.8 (c 1, CHCl3)Source of chirality: asymmetric synthesis (biotransformation)Absolute configuration: (R)

(R)-Styrene oxideC8H8OEe >99%[α]D20=-19.5 (c 1, CHCl3)Source of chirality: asymmetric synthesis (biotransformation)Absolute configuration: (R)