Читать книгу Enzyme-Based Organic Synthesis - Cheanyeh Cheng - Страница 30

There are natural organosulfur compounds such as sulfur containing amino acids (cysteine, methionine, and cystine), allicin, lipoic acid, and unnatural organosulfur compounds such as dibenzothiophene in petroleum products or penicillin in pharmaceutical products. Among the variety of organosulfur compounds, chiral organic sulfoxides (COSs) are useful chiral building blocks or stereodirecting groups in asymmetric synthesis of important pharmaceuticals that contain a functional sulfinyl group attached to the alkyl moieties [101, 102]. However, the preparation of COSs also can be obtained through sulfoxidation by the high regioselectivity and stereoselectivity of enzymes [103]. For example, the purified catalase‐peroxidase (KatG) characterized as a heme‐containing protein from the bacterium Bacillus pumillis was employed for stereoselective oxidation of β‐lactams, represented by penicillin‐G, penicillin‐V, and cephalosporin‐G to their R‐sulfoxides [104].

The use of co‐expression system that is the co‐expression of formate dehydrogenase from gene originated from Candida boidinii and the cyclohexanone monooxygenase (CHMO) gene cloned from Acinetobacter calcoaceticus NCIMB 9871 in E. coli BL21 has been used as the whole‐cell biocatalyst to selectively synthesize chiral R‐phenyl methyl sulfoxide (R‐PMSO) from thioanisole. In this reaction system, NADPH has also been regenerated to improve the catalytic efficiency [105]. Another strategy was utilized to selectively synthesize corresponding S‐sulfoxide from p‐chlorothioanisole as shown by Scheme 2.25 [106]. In this investigation, the asymmetric oxygenation of sulfide to S‐sulfoxide was with co‐expressed E. coli that contains the P450SMO gene from Rhodococcus sp. and the glucose dehydrogenase gene from Bacillus subtilis. In this study, NADPH was efficiently regenerated when glucose was supplied to the reaction.

Scheme 2.25 Synthesis of optically pure S‐sulfoxide by co‐expressed E. coli.

The enantioselective sulfoxidation of benzyl methyl sulfide to its corresponding S‐sulfoxide was performed by phenylacetone monooxygenase (PAMO) from Thermobifida fusca in a nonconventional Tris‐HCl buffer medium containing hydrophilic organic solvents such as polyethylene glycol (PEG), methanol (MeOH), acetonitrile, iso‐propanol, and alcohol with high conversion rate and moderate e.e.% [107]. The reaction also used glucose 6‐phosphate/glucose‐6‐phosphate dehydrogenase (G6P/G6PDH) as secondary ancillary system for regenerating the NADPH cofactor. An alternative method for producing enantiopure sulfoxides by direct asymmetric oxidation of prochiral sulfides was the optical resolution of racemic sulfoxides [108]. Therefore, S‐phenyl methyl sulfoxide (S‐PMSO) accompanied by a by‐product sulfone was formed at 93.7% ee(S) in a fed‐batch reaction with the use of bacterium Rhodococcus sp. ECU0066. For other substrates such as para‐substituted (methyl and chloro) PMSOs and ethyl phenyl sulfoxide, an S‐enantioselectivity (ee(S)) larger than 99.0% was also obtained.