1 research outputs found
Atroposelective Synthesis of Aldehydes via Alcohol Dehydrogenase-Catalyzed Stereodivergent Desymmetrization
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