Atroposelective Synthesis of Aldehydes via Alcohol Dehydrogenase-Catalyzed Stereodivergent Desymmetrization

作者：Mengjing Ye, Congcong Li, Dongguang Xiao, Ge Qu, Bo Yuan, Zhoutong Sun · 发表于：JACS Au · 年份：2024 · DOI：10.1021/jacsau.3c00814 · 被引用次数：29 · 研究领域：Axial and Atropisomeric Chirality Synthesis、Molecular spectroscopy and chirality、Sphingolipid Metabolism and Signaling

Axially chiral aldehydes have emerged recently as a unique class of motifs for drug design. However, few biocatalytic strategies have been reported to construct structurally diverse atropisomeric aldehydes. Herein, we describe the characterization of alcohol dehydrogenases to catalyze atroposelective desymmetrization of the biaryl dialdehydes. Investigations into the interactions between the substrate and key residues of the enzymes revealed the distinct origin of atroposelectivity. A panel of 13 atropisomeric monoaldehydes was synthesized with moderate to high enantioselectivity (up to >99% ee) and yields (up to 99%). Further derivatization allows enhancement of the diversity and application potential of the atropisomeric compounds. This study effectively expands the scope of enzymatic synthesis of atropisomeric aldehydes and provides insights into the binding modes and recognition mechanisms of such molecules.