Bioreduction of β‐ketosulfides Using Deep Eutectic Solvents as Cosolvents

ABSTRACT The β‐hydroxysulfide motif is present in both natural and synthetic compounds with notable bioactivities. Herein, the synthesis of a set of optically active ( R )‐ and ( S )‐β‐hydroxysulfides starting from β‐ketosulfides using ketoreductases (KREDs) in nonconventional media aqueous buffer/deep eutectic solvents (DESs) has been developed. Several Type III DESs have been tested as cosolvents, being observed for most of the biotransformations higher conversions and enantiomeric excesses in the presence of some glycerol‐ or ethylenglycol‐based DESs. Bioreductions can be performed up to 70% v/v of DESs with good conversions, demonstrating the high performance of these nonconventional media in biocatalyzed reductive processes. Additionally, it was observed that the lipase CalB partially retained activity in DES‐containing media for the hydrolysis of β‐alkylsulfide enol esters, thus being possible to develop a one‐pot, two‐enzyme cascade that combined CaalB‐catalyzed hydrolysis of a β‐alkylsulfide enol ester with the subsequent KRED reduction of the β‐ketosulfide obtained to the ( R )‐β‐hydroxysulfide in both sequential and concurrent ways, affording high stereoselectivity.