One-pot two-stage biocatalytic upgrading of biomass-derived aldehydes to optically active β-amino alcohols via sequential hydroxymethylation and asymmetric reduction amination

Abstract

Chiral β-amino alcohols are crucial building blocks in the synthesis of pharmaceutically active molecules and natural products. Developing green and sustainable methods for synthesizing chiral β-amino alcohols from renewable feedstocks continues to pose a significant challenge. Herein, we proposed a simple one-pot two-stage artificial cascade biocatalysis system for highly efficient conversion of renewable biomass-derived aldehydes into chiral β-amino alcohols with good yields and excellent enantioselectivity via sequential hydroxymethylation and asymmetric reduction amination. The initial stage involves converting aldehydes into α-hydroxy ketones by providing formaldehyde through benzaldehyde lyase-catalyzed hydroxymethylation. The subsequent stage is to convert α-hydroxy ketones into chiral β-amino alcohols through amine transaminase-catalyzed asymmetric reduction amination. Combining the two different types of reactions with two different enzymes, biomass-derived furfural 1a could be easily converted into (R)-2-amino-2-(furan-2-yl)ethanol ((R)-3a) and (S)-2-amino-2-(furan-2-yl)ethanol ((S)-3a) with up to 95% and 92% conversions and >99% ee, respectively. In addition, with this cascade biocatalysis, several enantiopure arylglycinols 3b–e were synthesized (39.4–99.0% conversions and >99% ee) from the biomass-derived benzaldehydes (1b–c) and benzaldehyde derivatives (1d–e). Furthermore, biotransformation on a preparative scale gave (S)-3a and (R)-3a in good yields (64.6% and 60.4%) and excellent ee (>99%). This study presents an eco-friendly and sustainable approach for synthesizing chiral β-amino alcohols using biomass-derived aldehydes.