Reduction Of Prochiral Ketones Research Articles

Highly stereoselective reduction of prochiral ketones by a bacterial reductase coupled with cofactor regeneration

A carbonyl reductase gene (yueD) from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli, and the encoded protein (BYueD) was purified to homogeneity and characterized. The NADPH-dependent reductase showed a broad substrate spectrum towards different aromatic ketones, and α- and β-ketoesters. Although the enantioselectivity was high to moderate for the reduction of α-ketoesters, all the tested β-ketoesters and aromatic ketones were reduced to the corresponding chiral alcohols in enantiomerically pure forms. Furthermore, the practical applicability of this enzyme was evaluated for the reduction of ethyl 4-chloro-3-oxobutanoate (1a). Using Escherichia coli cells coexpressing BYueD and glucose dehydrogenase, 215 g L(-1) (1.3 M) of 1a was stoichiometrically converted to ethyl (R)-4-chloro-3-hydroxybutanoate ((R)-1b) in an aqueous-toluene biphasic system by using a substrate fed-batch strategy, resulting in an overall hydroxyl product yield of 91.7% with enantiomeric purity of 99.6% ee.

Asymmetric transfer hydrogenation of acetophenone derivatives with novel chiral phosphinite based η 6- p-cymene/ruthenium(II) catalysts

Enantioselective reduction of prochiral ketones to optically active secondary alcohols is an important subject in synthetic organic chemistry because the resulting chiral alcohols are extremely useful, biologically active compounds. The new chiral ligands (2 R)-2-[benzyl{(2-((diphenylphosphanyl)oxy)ethyl)}amino]butyldiphenylphosphinite, 1 and (2 R)-2-[benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, 2 and the corresponding ruthenium(II) complexes 3 and 4 have been prepared. The structures of these complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. 31P–{ 1H} NMR, DEPT, 1H– 13C HETCOR or 1H– 1H COSY correlation experiments were used to confirm the spectral assignments. These ruthenium(II)–phosphinite complexes have been used as catalysts for the asymmetric transfer hydrogenation of acetophenone derivatives. Under optimized conditions, aromatic ketones were reduced in good conversions and in moderate to good enantioselectivities (up to 85% ee).

A density functional theory study of the enantioselective reduction of prochiral ketones promoted by chiral spiroborate esters

Recently, chiral spiroborate ester [(R)-2-((1,3,2-dioxaborolan-2-yloxy)methyl)pyrrolidine] has been experimentally employed as an effective chiral catalyst in the borane-mediated asymmetric reduction of prochiral ketones to produce the corresponding secondary alcohols. In this article, we have theoretically investigated the mechanism of the reduction using density functional theory. The results reveal that this reaction is accomplished via four steps. Fully geometry optimized reactants, products, transition states, and intermediates were obtained at the B3LYP/6-31G (d, p) level. The analysis of these results reveals one pathway that is more energetically favorable, and its associated geometries correlate well with the final products of the reaction. The further calculations show that the solvent effect of THF has no great influence on enantioselectivity of this reduction. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

ChemInform Abstract: Synthesis of Novel Chiral Ionic Liquid and Its Application in Reduction of Prochiral Ketones to the Corresponding Chiral Alcohols Using NaBH4.

AbstractThe optically active alcohols are obtained in low to moderate enantiomeric excess and in short reaction times (no yields given).

Enantioselective reduction of ketones and imines catalyzed by (CN-box)Re(V)-oxo complexes.

The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to 1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and 2) the enantioselective reduction of imines.

Enantioselective reduction of prochiral ketones by engineered bifunctional fusion proteins

NADPH-dependent oxidoreductases are useful catalysts for the production of chiral synthons. However, preparative applications of oxidoreductases require efficient methods for in situ regeneration of the expensive nicotinamide cofactors. An advantageous method for cofactor regeneration is the construction of bifunctional fusion proteins composed of two enzymes, one catalysing the reduction reaction and the other one mediating the recycling of cofactors. Herein, we describe the in-frame fusion between an NADP+-accepting mutant of FDH (formate dehydrogenase) from Mycobacterium vaccae N10 and KR [3-ketoacyl-(acyl-carrier-protein) reductase] from Synechococcus sp. strain PCC 7942. The generation of linker insertion mutants led to a fusion protein exhibiting 100 and 80% of the enzymatic activities of native KR and FDH respectively. Escherichia coli cells expressing the fusion protein showed an approx. 2-fold higher initial reaction rate in the production of chiral alcohols than cells expressing the enzymes separately. The application of the engineered fusion protein in whole-cell bioreduction of pentafluoroacetophenone resulted in a substrate conversion of 99.97% with an excellent enantiomeric excess of 99.9% (S)-1-(pentafluorophenyl)ethanol.

Studies on the application of organophosphorus reagents in asymmetric reactions

Owning to their structure diversity,organophosphorus compounds play an outstanding role in the asymmetric tranformations.They have been successfully employed as chiral ligand,chiral catalyst,chiral auxiliary,additive,substrate as well as chiral reagent in different type of asymmetric reactions.This account outlines our efforts on the application of organophosphorus compounds in some asymmetric reactions during the past seveval years,such as silylcyanation of aldehydes,desymmetrization of meso epoxide,Friedel-Crafts alkylation of indole,Michael addition to nitroolefins,aza-Henry reaction,aza-Morita-Baylis-Hillman reaction,borane reduction of prochiral ketones.

ChemInform Abstract: A New Family of Modular Chiral Ligands for the Catalytic Enantioselective Reduction of Prochiral Ketones.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Borane Reduction of Prochiral Ketones Using Aluminum Triethoxide and Chiral Amino Alcohols.

The asymmetric borane reduction of prochiral ketones with catalysts prepared in situ from aluminum triethoxide and chiral amino alcohols was examined, and the corresponding chiral alcohols were obtained in high optical purity.

ChemInform Abstract: Microgel-Supported Oxazaborolidines: Novel Catalysts for Enantioselective Reductions.

Abstract Microgel-bound oxazaborolidines have been prepared and used as catalysts in the enantioselective reduction of prochiral ketones. The preparation of these soluble, crosslinked polymer molecules was accomplished by solution polymerisation. The approach involved the preparation of microgels bearing free boronic acid functionalities and their subsequent conversion to oxazaborolidines. The selectivities of these supported catalysts are in most cases comparable to those achieved with low molecular weight analogues. The advantage of the application of microgel-bound catalysts is their good solubility together with low viscosity of the solution. Reagents of this type can easily be removed by ultrafiltration and the process can be performed in a continuous mode in a membrane reactor.

Flexibility of a biotinylated ligand in artificial metalloenzymes based on streptavidin--an insight from molecular dynamics simulations with classical and ab initio force fields.

In the field of enzymatic catalysis, creating activity from a non catalytic scaffold is a daunting task. Introduction of a catalytically active moiety within a protein scaffold offers an attractive means for the creation of artificial metalloenzymes. With this goal in mind, introduction of a biotinylated d6-piano-stool complex within streptavidin (SAV) affords enantioselective artificial transfer-hydrogenases for the reduction of prochiral ketones. Based on an X-ray crystal structure of a highly selective hybrid catalyst, displaying significant disorder around the biotinylated catalyst [η6-(p-cymene)Ru(Biot-p-L)Cl], we report on molecular dynamics simulations to shed light on the protein–cofactor interactions and contacts. The results of these simulations with classical force field indicate that the SAV-biotin and SAV-catalyst complexes are more stable than ligand-free SAV. The point mutations introduced did not affect significantly the overall behavior of SAV and, unexpectedly, the P64G substitution did not provide additional flexibility to the protein scaffold. The metal-cofactor proved to be conformationally flexible, and the S112K or P64G mutants proved to enhance this effect in the most pronounced way. The network of intermolecular hydrogen bonds is efficient at stabilizing the position of biotin, but much less at fixing the conformation of an extended biotinylated ligand. This leads to a relative conformational freedom of the metal-cofactor, and a poorly localized catalytic metal moiety. MD calculations with ab initio potential function suggest that the hydrogen bonds alone are not sufficient factors for full stabilization of the biotin. The hydrophobic biotin-binding pocket (and generally protein scaffold) maintains the hydrogen bonds between biotin and protein.Electronic supplementary materialThe online version of this article (doi:10.1007/s10822-010-9369-x) contains supplementary material, which is available to authorized users.

Synthesis of Novel Chiral Ionic Liquid and Its Application in Reduction of Prochiral Ketones to the Corresponding Chiral Alcohols Using NaBH4

A novel chiral ionic liquid (CIL) based on nicotinium salt has been synthesized and used as an efficient asymmetric chiral catalyst for reduction of acetophenone derivatives with NaBH4 in methanol at room temperature. The optically active alcohols were obtained in low to moderate enantiomeric excess in a short reaction time.

Synthesis, resolution, and applications of 3-amino-2,2-dimethyl-1,3-diphenylpropan-1-ol, a conformationally restricted 1,3-aminoalcohol

Efficient synthetic routes to both syn and anti diastereomers of a conformationally restricted 1,3-aminoalcohol were devised. Resolution of the aminoalcohols was accomplished through diastereomeric salt with R-(−)- O-acetyl mandelic acid. These aminoalcohols were examined as ligands for two standard reactions, namely, enantioselective addition of Et 2Zn to aldehydes and reduction of prochiral ketones with BH 3.

Hexahydropyrrolo[2,3‐b]indoles: A New Class of Structurally Rigid Tricyclic Skeleton for Oxazaborolidine‐Catalyzed Asymmetric Borane Reduction

AbstractA new class of structurally rigid tricyclic chiral ligands based on the hexahydropyrrolo[2,3‐b]indole skeleton has been rationally designed and the catalytic abilities in asymmetric catalysis have been shown in the enantioselective borane reduction of prochiral ketones to afford the chiral alcohols in excellent yields and high enantioselectivities (up to 97% ee).

Preparation and Characterization of Chiral Oxazaborolidine Complex Immobilized SBA-15 and Its Application in the Asymmetric Reduction of Prochiral Ketones

The immobilization of chiral oxazaborolidine complex in the well-ordered mesochannels of SBA-15 is demonstrated by a postsynthetic approach using 3-aminopropyltriethoxysilane as a reactive surface modifier. The immobilized catalysts are characterized by various techniques, such as XRD, nitrogen adsorption, HRSEM, UV/Vis diffuse reflectance spectroscopy, and FTIR spectroscopy. The catalysts are used for the enantioselective reduction of aromatic prochiral ketones. The activity of the chiral oxazaborolidine complex immobilized SBA-15 catalysts is also compared with that of the pure chiral oxazaborolidine complex, which is a homogeneous catalyst. It is found that the activity of the chiral complex immobilized SBA-15 heterogeneous catalyst is comparable with that of the homogeneous catalyst.

Candida tropicalis CE017: a new Brazilian enzymatic source for the bioreduction of aromatic prochiral ketones

The reactivity and stereoselectivity showed by a new strain of Candida tropicalis in the reduction of prochiral ketones have been compared with the ones previously attained in our laboratory using microorganisms from the Brazilian biodiversity. In this manner, Candida tropicalis has demonstrated its versatility as stereoselective agent in the bioreduction of a series of aromatic ketones. These prochiral compounds were converted into their corresponding optically alcohols with moderate to excellent stereopreference depending on the substrate structure. Among ketones tested, nitroacetophenones were enzymatically reduced to enantiopure (S)-alcohol with complete conversion.

Towards chiral diamines as chiral catalytic precursors for the borane-mediated enantioselective reduction of prochiral ketones

Two chiral diamines (3S)-3-anilinomethyl-1,2,3,4-tetrahydroisoquinoline (1) and (2R)-2-anilinomethylpiperidine (2) have been employed as chiral catalytic sources in the borane-mediated asymmetric reduction of prochiral ketones thus providing the resulting secondary alcohols in good enantiomeric purities (up to 81% ee).

A Continuously Operated Bimembrane Reactor Process for the Biocatalytic Production of (2R,5R)-Hexanediol

Alcohol dehydrogenase-catalyzed reductions of prochiral ketones to chiral alcohols require the regeneration of consumed cofactors such as NADH or NADPH. In the substrate-coupled cofactor regeneration approach, where 2-propanol is oxidized to acetone, complete conversion is inhibited by a thermodynamic limitation. This can be overcome by applying methods of in situ product removal techniques such as pervaporation. Here we present a new reactor concept which enables a continuous biocatalytic ketone reduction process with concurrent in situ removal of the byproduct acetone. In such a bimembrane reactor system recombinant Escherichia coli cells expressing alcohol dehydrogenase from Lactobacillus brevis were applied for the continuous reduction of 2,5-hexanedione. The product (2R,5R)-hexanediol could be synthesized with exceedingly high space-time yield of >170 g/(L·d) and catalyst usage (17.9 gP/gwetcellweight).

ChemInform Abstract: Chiral Ligand Derived from (1S,2R)‐Norephedrine as a Catalyst for Enantioselective Prochiral Ketone Reduction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Enantioselective Reduction of Prochiral Ketones Employing Sprouted Pisum sativa as Biocatalyst.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.