Tomoko Matsuda

Recent developments in asymmetric reduction of ketones with biocatalysts

Herein we review recent advances in the asymmetric reduction of ketones by biocatalysts. Included are discussions on recent developments in methodologies to control enantioselectivities of catalytic reactions, and examples of practical applications that reduce various types of ketones are also shown.

Asymmetric reduction of ketones by the acetone powder of Geotrichum candidum

Aromatic ketones, β-keto esters, and simple aliphatic ketones were reduced with excellent selectivity to the corresponding (S)-alcohols by using the acetone powder of Geotrichum candidum. This method is superior in reactivity and stereoselectivity to reduction by the whole-cell. The experimental conditions for the reduction system such as ratio of the biocatalyst to the substrate, kinds of coenzymes, alcohol for coenzyme regeneration, and buffer, pH, and reaction temperature were investigated, and stability and preservability of the biocatalyst were also examined. This method is very convenient for the synthesis of optically pure alcohols on a gram scale.

Reactions of supercritical alcohols with unsaturated hydrocarbons

Abstract The reactions of some supercritical alcohols were investigated using 1,1-diphenylethylene, styrene, allylbenzene, and diphenylacetylene as the reaction partners. 1,1-Diphenylethylene in supercritical methanol was hydroxymethylated to afford 3,3-diphenyl-1-propanol as the major product. The alkenes containing a single and no conjugate phenyl group were also hydroxymethylated in supercritical methanol, but the reaction rates were significantly reduced when compared with that for 1,1-diphenylethylene. Styrene was converted to the hydroxyalkylated products in supercritical ethanol and 2-propanol as well as in supercritical methanol. The rates of the hydroxyalkylation of styrene were strongly dependent on the structures of the supercritical alcohols; the order of reactivity was 2-propanol>ethanol>methanol. The relation between the structures of the alcohols and the rates of hydroxyalkylation suggests that the reaction begins with an attack on the electrophile ( + CR 2 OH or δ+ CR 2 OH) by the pi electrons of the styrene double bond. All the examined alkenes afforded their hydrogenated derivatives other than the hydroxyalkylated ones. In addition, supercritical alcohols acted as hydroxyalkylating or hydrogenating reagents for the triple bond in the reaction with diphenylacetylene.

MICROBIAL DERACEMIZATION OF 1-ARYLETHANOL

Abstract When racemic 1-arylethanol is reacted with Geotrichum candidum IFO 5767 in water, ( R )-1-arylethanol is obtained in high yield with excellent ee. It has been found that ( S )-1-arylethanol is converted into the antipode via oxidation to the corresponding aryl methyl ketone and successive reduction of the ketone to the ( R )-alcohol. Ally alcohol as an additive enhances deracemization.

Recent progress in biocatalysis using supercritical carbon dioxide

The latest advances in biocatalysis using supercritical carbon dioxide (scCO(2)) are reviewed. Stability and stabilization methodologies of enzymes in scCO(2) as well as reactions for organic synthesis are described. Especially, varieties of examples for lipase-catalyzed synthesis of chiral compounds using scCO(2) are given. Furthermore, asymmetric reduction by alcohol dehydrogenase in scCO(2) and carboxylation by decarboxylase in scCO(2) are also introduced.

Control on enantioselectivity with pressure for lipase-catalyzed esterification in supercritical carbon dioxide

Abstract The enantioselectivity of lipase-catalyzed esterification of 1-( p -chlorophenyl)-2,2,2-trifluoroethanol in supercritical carbon dioxide changed continuously from E =10 to 50 by decreasing the pressure at 55°C. The effect of the solvent on enantioselectivity was examined without changing the kind of solvent.

Organic synthesis using enzymes in supercritical carbon dioxide

Enzymes have been used in supercritical carbon dioxide (scCO2) rather than in the conventional media to make enzyme reactions greener. This review introduces some enzymatic asymmetric synthesis in scCO2 such as esterification by a lipase and reduction by an alcohol dehydrogenase. A carboxylation by a decarboxylase is also described.

Asymmetric reduction of trifluoromethyl ketones containing a sulfur functionality by the alcohol dehydrogenase from Geotrichum

Abstract The reduction of trifluoromethyl ketones containing a sulfur functionality by the crude alcohol dehydrogenase from Geotrichum proceeded successfully, and the corresponding optically active alcohols were synthesized with high yields and excellent enantioselectivities.

Different stereochemistry for the reduction of trifluoromethyl ketones and methyl ketones catalyzed by alcohol dehydrogenase from Geotrichum

Abstract Reduction of trifluoromethyl ketones by a crude alcohol dehydrogenase from Geotrichum afford (S)-trifluoromethyl carbinols in excellent ee, whereas the reduction of methyl ketones gives the corresponding alcohols of the opposite configuration in excellent ee.

Asymmetric synthesis of (R)-2-chloro-1-(m-chlorophenyl)ethanol using acetone powder of Geotrichum candidum

The asymmetric synthesis of (R)-2-chloro-1-(m-chlorophenyl)ethanol, a precursor for a key intermediate of an important class of drugs, was achieved by reduction of the corresponding ketone using an acetone powder of Geotrichum candidum with 98% ee and 94% yield based on the starting amount of ketone.