Biocatalytic asymmetric ring-opening of meso-epoxides to enantiopure cyclic trans-β-amino alcohols involving a key amine transaminase

Abstract

Chiral cyclic β-amino alcohols are vital building blocks for the synthesis of numerous pharmaceuticals and bioactive molecules. Asymmetric ring-opening of cyclic meso-epoxides is a straightforward and appealing method for their synthesis. However, developing an environmentally friendly and cost-effective approach for this process remains elusive. Herein, the synthesis of enantiomerically pure cyclic β-amino alcohols through a fully biocatalytic asymmetric ring-opening of cyclic meso-epoxides is described. A novel amine transaminase (CepTA) from Capronia epimyces with comparable activity and excellent enantioselectivity toward small molecule cyclic α-hydroxy ketones was discovered and proved to be efficient on a wide range of substrates. Homology modelling, molecular docking, and molecular dynamics simulations were also performed to elucidate the highly efficient catalytic mechanisms of CepTA for small cyclic α-hydroxy ketones. The asymmetric ring-opening of cyclic meso-epoxides (4′j–k) was successfully achieved by using combined recombinant E. coli (SpEH-AnDDH-BsLDH) and E. coli (CepTA) resting cells, leading to the production of cyclic (1R,2R)-trans-β-amino alcohols (1′j–k) up to 81.8% conversions and >99% ee. This study marks the first instance of achieving fully biocatalytic asymmetric ring-opening of meso-epoxides to chiral cyclic β-amino alcohols, offering a novel pathway for the environmentally friendly synthesis of chiral cyclic β-amino alcohols from readily available, cost-effective meso-epoxides.