Synthesis of single stereoisomers of 2,2-disubstituted 3-hydroxycyclohexane-1-ones via enzymatic desymmetric reduction of the 1,3-cyclohexanediones

Abstract

Chiral 3-hydroxycyclohexane-1-ones are widely used as building blocks in the synthesis of natural products and bioactive compounds, and preparation of their single stereoisomers is still quite challenging. Through screening the available carbonyl reductases, two enzymes were found to catalyze the desymmetric reduction of 2-benzyl-2-methyl-1,3-cylcohexanedione analogues to give the corresponding (2R,3R) or (2S,3S) 3-hydroxycyclohexane-1-ones bearing an all-carbon chiral quaternary center with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (up to >99:1 dr). These results demonstrated the carbonyl reductases as powerful catalysts for the desymmetric reduction of 1,3-cylcohexanediones, although further studies are required to search for more enzymes to expand the substrate scope and stereopreference.

Keywords

• 2,2-Disubstituted 1,3-cyclohexanedione
• Desymmetric reduction
• Carbonyl reductase
• Chiral cyclic 3-hydroxy ketone
• Biocatalysis