Bioreduction asymmetric

Stuermer, R., Hauer, B., Hall, M. and Faber, K. (2007) Asymmetric bioreduction of activated C C bonds using enoate reductases from the old yellow enzyme family. Current Opinion in Chemical Biology, 11, 203-213. 

Inoue, K., Makino, Y., Dairi, T. and Itoh, N. (2006) Gene cloning and expression of Leifsonia alcohol dehydrogenase (LSADH) involved in asymmetric hydrogen-transfer bioreduction to produce (/ )-form chiral alcohols. Bioscience Biotechnology and Biochemistry, 70 (2), 418-426. 

Itoh, N., Nakamura, M., Inoue, K. and Makino, Y. (2007) Continuous production of chiral 1,3-butanediol using immobilized biocatalysts in a packed bed reactor promising biocatalysis method with an asymmetric hydrogen-transfer bioreduction. Applied Microbiology and Biotechnology, 75 (6), 1249-1256. 

Oxidoreductases are, after lipases, the second most-used kinds of biocatalysts in organic synthesis. Two main processes have been reported using this type of enzymes-bioreduction of carbonyl groups [39] and biohydroxylation of non-activated substrates [40]. However, in recent few years other processes such as deracemization of amines or alcohols [41] and enzymatic Baeyer-Villiger reactions of ketones and aldehydes [42] are being used with great utility in asymmetric synthesis. 

K. Lorraine, S. King, R. Greasham, and M. Chartrain, Asymmetric bioreduction of a ketosulfone to the corresponding trans-hydroxysulfone by the yeast Rhodotorula rubra MY 2169, Enzyme Microb. Technol. 1996, 39, 250-255. 

Flail M, Stueckler C et al (2008) Asymmetric bioreduction of activated C=C bonds using Zymomonas mobilis NCR enoate reductase and old yellow enzymes OYE 1-3 from yeasts. Eur J Org Chem 2008 1511-1516... 

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. 

Hall, M., Stueckler, C., Kroutil, W., Macheroux, P., and Faber, K. 2007. Asymmetric bioreduction of activated alkenes using cloned 12-oxophytodienoate reductase isoenzymes OFR-1 and OPR-3 from Lycopersicon esculentum (Tomato) A striking change of stereoselectivity. Angew. Chem. Int. Ed., 46, 3934-3937. 

Swiderska, M. A., and Stewart, J. D. 2006b. Asymmetric bioreduction of P-nitro acrylates as a route to chiral p2-amino acids. Org. Lett., 8, 6131-6133. 

Bioreduction of ketones often leads to (he creation of an asymmetric center and. thereby, two possible stereoisomeric alcohols. " For example, reduction of acetophenone by a soluble rabbit kidney reductase leads to the enantiomeric alcohols (5)(-)- and (R)( + )-mcthylphen lcarbinol. with the (.V)(-) isomer predominating (3 1 ratio). The preferential formation of one stereoisomer over the other is termed product stereoselectivity in drug metabolism. " Mechanistically, ketone reduction involves a "hydride" transfer from the reduced nicotinamide moiety of the cofactor NADPH or NADH to (he carbonyl carbon atom of the ketone. It is generally agreed that this step proceeds with considerable stereoselectivity." Consequently, it is not surprising to find many reports of xenobiotic ketones that are i uced prefer-emi ly to a predominant stereoisomer. Often, ketone reduction yields dcohol metabolites that arc pharmacologically active. 

Here the biotransformation (Fig. 19-6) is preferred over the chemical reduction with commercially available asymmetric catalysts (BH3- or noble-metal-based), since with the chemocatalysts the desired high enantiomeric excess (ee > 98%, 99.8% after purification) is not achievable. Since the ketone has only a very low solubility in the aqueous phase, 1 kg ketone is added as solution in 4 L 0.9 M H2SO4 to the bioreactor. The bioreduction is essentially carried out in a two-phase system, consisting of the aqueous phase and small droplets made up of substrate and product. The downstream processing consists of multiple extraction steps with methyl ethyl ketone and precipitation induced by pH titration of the pyridine functional group (pfCa = 4.66) with NaOH. The (R)-amino alcohol is an important intermediate for the synthesis of (1-3-agonists that can be used for obesity therapy and to decrease the level of associated type II diabetes, coronary artery disease and hypertension. 

Hunt, P. Salmon, D. Roush, S. Yamazaki, T. Wang, E. Grabowski, B. Buckland, R. Grea-sham, Asymmetric bioreduction of (2-(4-ni-tro-phenyl)-N-(2-oxo-2-pyridin-3-yl-ethyl)-acetamide) to its corresponding (R) alcohol [(R)-N-(2-hydroxy-2-pyridin-3-yl-ethyl)-2-(4-nitro-phenyl)-acetamide] by using Candida sorbophila MY 1833, Enz. Microb. Tech-nol. 1999, 25, 489-496. 

Application of bioreduction to the asymmetric syntheses of chiral drugs 01MI118. 

Scheme 2.134 Asymmetric bioreduction of activated alkenes using flavin-dependent ene-reductases...

The following crude guidelines for the asymmetric bioreduction of activated alkenes using ene-reductases can be delineated ... 

Recent breakthroughs in the cloning of oxygen-stable ene-reductases enables the asymmetric bioreduction of activated carbon-carbon double bonds for preparative-scale applications. NADH recycling is performed on industrial scale, for the more sensitive NADPH analog improvements would be desirable. 

M., and Faber, K. (2012) Asymmetric bioreduction of activated alkenes to industrially relevant optically active compoimds./. Biotechnd., 162,... 

N., and Faber, K. (2010) Nicotinamide-independent asymmetric bioreduction of C=C-bonds via disproportionation of enones by enoate reductases. Tetrahedron, 66, 663-667. 

Mueller, N.J., Stueckler, C., Hauer, B., Baudendistel, N., Housden, H., Bruce, N. C., and Faber, K. (2010) The substrate spectra of pentaerythritol tetranitrate reductase, morphinone reductase, N-ethylmaleimide reductase and estrogen-binding protein in the asymmetric bioreduction of activated alkenes. Adv. Synth. Catal., 352, 387-394. 

Toogood, H.S., Fryszkowska, A., Hare, V., Fisher, K., Roujeinikova, A., Leys, D., Gardiner, J.M., Stephens, G.M., and Scmtton, N.S. (2010) Structure-based insight into the asymmetric bioreduction of the C=C double bond of a,p-imsaturated nitroalkenes by pentaerythritol tetranitrate reductase. Adv. Synth. Catal., 350, 2789-2803. 

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