Kinetic Hydrolysis of Sulfinamides toward S(IV) Chirality Enabled by Visible-Light-Excited Ene-Reductases

Previously
reported enzymatic approaches to chiral S(IV)
stereogenic
compounds were limited to the natural enzyme reactivity. Herein, we
report a photoenzymatic kinetic resolution strategy by repurposing
ene-reductases as unnatural photohydrolases, synthesizing enantioenriched
arylsulfinamides (up to 99.5:0.5 er). Mechanistic investigations and
computational studies suggest an excited ene-reductase-triggered nitrogen-centered
radical (NCR) pathway. This work further demonstrates the potential
for reprogramming enzyme functionality through direct visible-light
excitation and provides an alternative biocatalytic route to chiral
sulfinamides.