Unconventional Biocatalytic Approaches to the Synthesis of Chiral Sulfoxides

Abstract

Sulfoxides are a class of organic compounds that find wide application in medicinal and organic chemistry. Several biocatalytic approaches have been developed to synthesise enantioenriched sulfoxides, mainly by exploiting oxidative enzymes. Recently, the use of reductive enzymes such as Msr and Dms has emerged as a new, alternative method to obtain enantiopure sulfoxides from racemic mixtures. In parallel, novel oxidative approaches, employing nonclassical solvents such as ionic liquids (ILs) and deep eutectic solvents (DESs), have been developed as greener and more sustainable biocatalytic synthetic pathways. This minireview aims highlights the recent advances made in the biocatalytic synthesis of enantioenriched sulfoxides by employing such unconventional approaches.

Keywords: biocatalysis; deep eutectics; ionic liquids; reductive enzymes; sulfoxides.

Figure 1

Natural sulfoxide‐ and sulfoxide‐containing drugs and ligands.

Scheme 1

Synthesis of sulfoxides by using a whole E. coli cell system overexpressing pmMsrA.

Scheme 2

Conversions of racemic sulfoxides using the crude pmMsrA‐DTT system.

Scheme 3

Conversion of racemic sulfoxides by using the crude paMsrA‐DTT system.

Scheme 4

Conversion of racemic sulfoxides by using a whole E. coli cell system overexpressing akMsrB.

Scheme 5

Deracemisation of racemic sulfoxides in a biphasic aqueous buffer/decane system by using whole cell MsrA and oxaziridine 13.

Scheme 6

Selectivity of DmsABC found in different anaerobic bacteria species.

Scheme 7

Kinetic resolution of alkyl aryl sulfoxides by using DmsABC.

Scheme 8

Mechanism of the electroenzymatic kinetic resolution of rac‐18 a–c.

Scheme 9

Chemoenzymatic deracemisation of rac‐19 by using whole‐cell E. coli DmsABC.

Scheme 10

GOX‐/Cip‐catalysed enantioselective sulfoxidation of aryl sulfoxides in IL [BMIM]PF₆.

Scheme 11

CPO‐catalysed sulfoxidation of methyl phenyl sulfide 23 in ILs.

Scheme 12

Asymmetric sulfoxidations with P450pyr in a KP Buffer/IL system.

Scheme 13

Synthesis of (R)‐modafinil 29 by using CPO from C. fumago in a biphasic aqueous buffer/IL.

Scheme 14

Bienzymatic sulfoxidation of 30 by using AnChOx and rAaeUPO.