Stereoselectivity biochemical reductions

Kashiyama, E. Yokoi, T. Todaka, T. Odomi, M. Kamataki, T. Chiral inversion of drug role of intestinal bacteria in the stereoselective sulphoxide reduction of flosequinan. Biochem. Pharmacol. 1994, 48,... 

Finally, a stereo chemically controlled reduction to give the axial alcohol (this would be the stereoselectivity expected with NaBH4 for example see Chapter 18) gives myo-inositol. The number and position of the phosphate esters can be controlled biochemically. This control is vital in the biological activity and would be difficult in the laboratory. 

Wada, M., Kataoka, M., Kawabata, H., Yasohara, Y., Kizaki, N., Hasegawa, J., and Shimizu, S. 1998. Purification and characterization of NADPH-dependent carbonyl reductase, involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida magnoliae. Biosci. Biotechnol. Biochem., 62, 280-285. 

A MECHANISM FOR THE REACTION ] Reduction of Aldehydes and Ketones by Hydride Transfer 548 THE CHEMISTRY OF... Alcohol Dehydrogenase—A Biochemical Hydride Reagent 548 THE CHEMISTRY OF... Stereoselective Reductions of Carbonyl Groups 550... 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

Miya H, Kawada M, Sugiyama Y. Stereoselective reduction of ethyl 2-methyl-3-oxobutanoate by bacteria. Biosci. Biotechnol. Biochem. 1996 60 95-98. 

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