Chemo-enzymatic synthesis of chiral precursor molecules with chiral ring hydroxyenone and acetoxyenone structures

Abstract

A biocatalytic transformation has the potential to perform organic reactions that are quite challenging to achieve with synthetic organic chemistry. They also catalyze these reactions with a chemo and enantio selective manner. The discovery and development of new chemoenzymatic methods for the synthesis of these chiral structures is essential to the production of a wide range of bioactive compounds. In this study, two important pharmaceutical precursors were synthesized chemoenzymatically and subjected to biocatalytic conversions with different dehydrogenases. One of these compound is an α-acetoxy enone structure 4-methoxy-2-oxacyclohex-3-enyl acetate and the other is an α-hydroxy ketone 6-hydroxy-3-methoxycycyclohex-2-enone. To obtain these pharmaceutical precursors, 3-methoxy-cyclohex-2-enone was prepared using 1,3-diketone as a starting material. After obtaining this material, α-acetoxy enone was synthesized by chemical acetylation and α-hydroxy ketone prepared by enzymatic deacetylation. The structure of these products was elucidated by NMR analysis. In addition, biocatalytic reduction reactions involving the enzymes galactitol dehydrogenase (GatDH), shikimate dehydrogenase (SDH) and diaphorase were carried out with these products.