Sulfoxidation cyclohexanone monooxygenase

Walsh and coworkers oxidized ethyl p-tolyl sulfide on an analytical scale to the S-sulfoxide of 64% enantiomeric purity using a bacterial flavoenzyme cyclohexanone monooxygenase derived from Adnetobacter . Using a flavin adenine dinucleotide containing monooxygenase purified from hog liver microsomes yielded the R-sulfoxide of 90% enantiomeric purity. HPLC on a column containing a 3,5-dinitrobenzoyl-D-phenylglycine chiral stationary phase was used to determine the optical purity of the sulfoxides. 

Light DR, Waxman DJ, Walsh C. 1982. Studies on the chirality of sulfoxidation catalyzed by bacterial flavoenzyme cyclohexanone monooxygenase and hog liver flavin adenine dinucleotide containing monooxygenase. Biochemistry 21 2490-2498. 

Stereoselective Synthesis of )0-Hydroxy Sulfoxides Catalyzed by Cyclohexanone Monooxygenase... 

Colonna, S., Gaggero, N., Pasta, P., Ottolina G., Enantioselective oxidation of sulfides to sulfoxides catalysed by bacterial cyclohexanone monooxygenases. Chem. Commun., 1996, 2303. 

The (S)-(-)-sulfoxide is predominantly produced (82 % S, 18 % R) from p-tolyl ethyl sulfide when cyclohexanone monooxygenase from Acinetobacter sp. NCIB 9871191 was used, whereas the the FAD-containing monooxygenase from hog liver micro-somes oxidizes p-tolyl ethyl sulfide to yield the (R)-(+)-sulfoxide enantiomer as the major product (95 % R, 5 % S) 15). 

Scheme 19. Directed evolution of a cyclohexanone monooxygenase for the asymmetric sulfoxidation of a prochiral thioether.

A systematic study of the sulfoxidation by cyclohexanone monooxygenase from Acinetobacter using as the substrates many alkyl aryl sulfides, dialkyl sulfides and dialkyl disulfides has been carried out by Carrea, Colonna, and colleagues in the presence of NADP and a NADPH-regenerating system [143,144]. Chemical yields are good (at 0.8 mmol scale), with wide variations of ee s (from 0 to 98%) according to the structure of the sulfides. 

Cyclohexanone and Cyclopentanone Monooxygenases as Baeyer-Villigerases and Sulfoxidation Catalysts... 

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