Biocatalytic dynamic kinetic reductive resolution with ketoreductase from Klebsiella pneumoniae: the asymmetric synthesis of functionalized tetrahydropyrans?

Organic & Biomolecular Chemistry Pub Date: 2019-08-31 DOI: 10.1039/C9OB01681C

Abstract

Ketoreductase from growing cells of Klebsiella pneumoniae (NBRC 3319) acts as an efficient reagent for converting racemic α-benzyl/cinnamyl substituted-β-ketoesters to the corresponding β-hydroxy esters with excellent yields and stereoselectivities (ee and de >99 %). The reactions described herein followed a biocatalytic dynamic kinetic reductive resolution (DKRR) pathway, which is reported for the first time with such substrates. It was found that the enzyme system can accept substituted mono-aryl rings with different electronic natures. In addition, it also accepts a substituted naphthyl ring and heteroaryl ring in the α-position of the parent β-ketoester. The synthesized enantiopure β-hydroxy esters were then synthetically manipulated to valuable tetrahydropyran building blocks.

Graphical abstract: Biocatalytic dynamic kinetic reductive resolution with ketoreductase from Klebsiella pneumoniae: the asymmetric synthesis of functionalized tetrahydropyrans
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