Enzymic Asymmetric Carbonyl Reductions

Enzymic Asymmetric Carbonyl Reductions. Microbial reduction of ketones continues to result in the highest optical yields of chiral 

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Asymmetric Carbonyl Reduction. The enzyme-like CBS catalysts (e.g. 20) developed by Corey 25) have been applied to the synthesis of arylethanolamines. Recent reports documenting successful enantioselective synthesis of denopamine 18 26) in conjunction with the remarkably high enantioselectivities obtained with these catalysts provided the impetus for our successful approach to R-FNEs. The synthesis began with the production of chloroketones 19b,d from aldehydes 10b,d by a documented procedure (27) (Scheme 2). Reduction of 19b,d with BHa THF in the... 

A bioreduction system might be applied to many NAD(P)H-dependent enzyme reactions other than carbonyl reduction. Recently, two novel old yellow enzymes (OYEs) catalyzing the asymmetric hydrogenation of C=C bonds were found and applied to a bioreduction system for the production of double chiral compounds. 

Kataoka, M., Nomura, Y., Shimizu, S., and Yamada, H. 1992a. Enzymes involved in the NADPH regeneration system coupled with asymmetric reduction of carbonyl compounds in microorganisms. Biosci. Biotech. Biochem., 56,820-821. 

In contrast, there are now many examples in the literature to indicate that, when presented with organic compounds already labelled with fluorine, enzymes may be tolerant to the presence of fluorine, depending on the number of C-F bonds and their location [89, 90]. For example, baker s yeast may lead to significant asymmetric reduction of carbonyl (Figure 1.7). 

Enzymes distinguish also between the two faces of trigonal atoms Cabx, most frequently encountered as part of a double-bond system. An example in this respect is the distinguishing between the A and B side of pyridine nucleotides by dehydrogenases (C 2.1.1). Other examples are reductions at asymmetrically substituted carbonyl groups, e.g., reduction of acetaldehyde by alcohol dehydrogenase (D 2), and additions to carbon-carbon double bonds. 

Examples of this kind of enantiomorphic or chiral selectivity are now being found in organic synthesis. Asymmetric synthesis, for example, has been demonstrated with stereo-controlled Michael addition in the synthesis of beta-lactams using chiral catalysts, where an acyl ligand such as acetyl is bound to cyclo-pentadiene carbonyl triphenylphosphine. Essentially complete enantiomorphic selectivity has been achieved in this Michael addition synthesis. Another case is enantio-morhic ketone reduction in ethylbenzene reduction in the ethylation of benzaldehyde. Using chiral catalysts, 97% selectivity has been achieved. Closely related research involves the making of catalytic antibodies and hybrid enzymes. ... 

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