- Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation
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Two cis-1,2-diol-type chiral ligands (T1 and T2) and their tri-coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dati
- Kilic, Ahmet,Balci, Tu?ba Ersayan,Arslan, Nevin,Aydemir, Murat,Durap, Feyyaz,Okumu?, Veysi,Tekin, Recep
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- Efficient synthesis of enantiopure amines from alcohols using resting: E. coli cells and ammonia
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α-Chiral amines are pivotal building blocks for chemical manufacturing. Stereoselective amination of alcohols is receiving increased interest due to its higher atom-efficiency and overall improved environmental footprint compared with other chemocatalytic and biocatalytic methods. We previously developed a hydrogen-borrowing amination by combining an alcohol dehydrogenase (ADH) with an amine dehydrogenase (AmDH) in vitro. Herein, we implemented the ADH-AmDH bioamination in resting Escherichia coli cells for the first time. Different genetic constructs were created and tested in order to obtain balanced expression levels of the dehydrogenase enzymes in E. coli. Using the optimized constructs, the influence of several parameters towards the productivity of the system were investigated such as the intracellular NAD+/NADH redox balance, the cell loading, the survival rate of recombinant E. coli cells, the possible toxicity of the components of the reaction at different concentrations and the influence of different substrates and cosolvents. In particular, the cofactor redox-balance for the bioamination was maintained by the addition of moderate and precise amounts of glucose. Higher concentrations of certain amine products resulted in toxicity and cell death, which could be alleviated by the addition of a co-solvent. Notably, amine formation was consistent using several independently grown E. coli batches. The optimized E. coli/ADH-AmDH strains produced enantiopure amines from the alcohols with up to 80% conversion and a molar productivity up to 15 mM. Practical applicability was demonstrated in a gram-scale biotransformation. In summary, the present E. coli-ADH-AmDH system represents an important advancement towards the development of 'green', efficient and selective biocatalytic processes for the amination of alcohols.
- Houwman, Joseline A.,Knaus, Tanja,Costa, Magda,Mutti, Francesco G.
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supporting information
p. 3846 - 3857
(2019/07/31)
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- Biocatalytic Racemization Employing TeSADH: Substrate Scope and Organic Solvent Compatibility for Dynamic Kinetic Resolution
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Racemization in combination with a kinetic resolution is the base for a dynamic kinetic resolution (DKR). Biocatalytic racemization was successfully performed for a broad scope of sec-alcohols by employing a single alcohol dehydrogenase (ADH) variant from Thermoanaerobacter pseudoethanolicus (formerly T. ethanolicus; TeSADH W110A I86A C295A). The catalyst employed as a lyophilized whole cell preparation or cell free extract, which tolerated various non-water miscible organic solvents under micro-aqueous or two-phase conditions, whereby cyclohexane and n-hexane suited best. Various concepts for combining the enzymatic racemization with an enzymatic kinetic resolution to achieve overall a bis-enzymatic DKR were evaluated. A proof of concept showed a successful DKR with racemization in aqueous phase combined with acylation in the organic phase.
- Pop?oński, Jaros?aw,Reiter, Tamara,Kroutil, Wolfgang
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p. 763 - 768
(2018/02/27)
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- Fungal mediated kinetic resolution of racemic acetates to (R)-alcohols using Fusarium proliferatum
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Fungal mediated kinetic resolution of seven acyclic/aromatic acetates was achieved using Fusarium proliferatum to furnish (R)-alcohols in high enantiomeric excess (>95%). The kinetic resolution was established as one-pot two-step de-esterification/oxidation biocatalytic process. Further, the preparative scale synthesis of (R)-(+)-1-phenylethanol was accomplished through de-esterification/oxidation of (±)-1-phenylethyl acetate using the whole cell of F. proliferatum NCIM 1105.
- Jadhav, Dipesh D.,Patil, Harshal S.,Chaya, Patil S.,Thulasiram, Hirekodathakallu V.
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p. 4563 - 4567
(2016/09/23)
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- Screening, Molecular Cloning, and Biochemical Characterization of an Alcohol Dehydrogenase from Pichia pastoris Useful for the Kinetic Resolution of a Racemic β-Hydroxy-β-trifluoromethyl Ketone
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The stereoselective synthesis of chiral 1,3-diols with the aid of biocatalysts is an attractive tool in organic chemistry. Besides the reduction of diketones, an alternative approach consists of the stereoselective reduction of β-hydroxy ketones (aldols). Thus, we screened for an alcohol dehydrogenase (ADH) that would selectively reduce a β-hydroxy-β-trifluoromethyl ketone. One potential starting material for this process is readily available by aldol addition of acetone to 2,2,2-trifluoroacetophenone. Over 200 strains were screened, and only a few yeast strains showed stereoselective reduction activities. The enzyme responsible for the reduction of the β-hydroxy-β-trifluoromethyl ketone was identified after purification and subsequent MALDI-TOF mass spectrometric analysis. As a result, a new NADP+-dependent ADH from Pichia pastoris (PPADH) was identified and confirmed to be capable of stereospecific and diastereoselective reduction of the β-hydroxy-β-trifluoromethyl ketone to its corresponding 1,3-diol. The gene encoding PPADH was cloned and heterologously expressed in Escherichia coli BL21(DE3). To determine the influence of an N- or C-terminal His-tag fusion, three different recombinant plasmids were constructed. Interestingly, the variant with the N-terminal His-tag showed the highest activity; consequently, this variant was purified and characterized. Kinetic parameters and the dependency of activity on pH and temperature were determined. PPADH shows a substrate preference for the reduction of linear and branched aliphatic aldehydes. Surprisingly, the enzyme shows no comparable activity towards ketones other than the β-hydroxy-β-trifluoromethyl ketone.
- Bulut, Dalia,Hummel, Werner,Gr?ger, Harald,Duangdee, Nongnaphat,Berkessel, Albrecht
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p. 1349 - 1358
(2016/12/24)
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- Discrimination of the prochiral hydrogens at the C-2 position of n-alkanes by the methane/ammonia monooxygenase family proteins
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The selectivity of ammonia monooxygenase from Nitrosomonas europaea (AMO-Ne) for the oxidation of C4-C8n-alkanes to the corresponding alcohol isomers was examined to show the ability of AMO-Ne to recognize the n-alkane orientation within the catalytic site. AMO-Ne in whole cells produces 1- and 2-alcohols from C4-C8n-alkanes, and the regioselectivity is dependent on the length of the carbon chain. 2-Alcohols produced from C4-C7n-alkanes were predominantly either the R- or S-enantiomers, while 2-octanol produced from n-octane was racemic. These results indicate that AMO-Ne can discriminate between the prochiral hydrogens at the C-2 position, with the degree of discrimination varying according to the n-alkane. Compared to the particulate methane monooxygenase (pMMO) of Methylococcus capsulatus (Bath) and that of Methylosinus trichosporium OB3b, AMO-Ne showed a distinct ability to discriminate between the orientation of n-butane and n-pentane in the catalytic site.
- Miyaji, Akimitsu,Miyoshi, Teppei,Motokura, Ken,Baba, Toshihide
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p. 8261 - 8270
(2015/08/03)
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- Ruthenium-catalyzed oxidative kinetic resolution of unactivated and activated secondary alcohols with air as the hydrogen acceptor at room temperature
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Enantiopure alcohols are versatile building blocks for asymmetric synthesis and the kinetic resolution (KR) of racemic alcohols is a reliable method for preparing them. Although many KR methods have been developed, oxidative kinetic resolution (OKR), in which dioxygen is used as the hydrogen acceptor, is the most atom-efficient. Dioxygen is ubiquitous in air, which is abundant and safe to handle. Therefore, OKR with air has been intensively investigated and the OKR of benzylic alcohols was recently achieved by using an Ir catalyst without any adjuvant. However, the OKR of unactivated alcohols remains a challenge. An [(aqua)Ru(salen)] catalyzed OKR with air as the hydrogen acceptor was developed, in which the aqua ligand is exchanged with alcohol and the Ru complex undergoes single electron transfer to dioxygen and subsequent alcohol oxidation. This OKR can be applied without any adjuvant to activated and unactivated alcohols with good to high enantioselectivity. The unique influence of substrate inhibition on the enantioselectivity of the OKR is also described. Alcohol resolution: An (aqua)ruthenium salen complex catalyzes the efficient oxidative kinetic resolution of both activated and unactivated secondary alcohols with air as the hydrogen acceptor at room temperature. The reaction is compatible with various functional groups, including halogen, ether, silyl ether, and ester groups. The reaction rate is lower at higher substrate concentrations as a result of substrate inhibition.
- Mizoguchi, Hirotaka,Uchida, Tatsuya,Katsuki, Tsutomu
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supporting information
p. 3178 - 3182
(2014/04/03)
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- Highly enantioselective Rh-catalysed hydrogenation of 1-alkyl vinyl esters using phosphine-phosphoramidite ligands
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MatPhos, a good mate for hard tasks: The asymmetric hydrogenation of 1-alkyl vinyl esters, thwarted so far by mediocre ee values and low activities, can now be achieved with MatPhos/Rh catalysts with ee values of 96-99 % for a variety of substrates at low catalyst loadings (0.1-1 mol %) and under mild conditions (5-20 bar H2, room temperature). After hydrolysis, the corresponding chiral secondary alkyl alcohols can be obtained in high enantiopurities providing a general and practical route to this important product class. Copyright
- Konrad, Tina Maria,Schmitz, Pascal,Leitner, Walter,Francio, Giancarlo
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supporting information
p. 13299 - 13303
(2013/10/08)
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- Phosphorus-bearing axially chiral biaryls by catalytic asymmetric cross-cyclotrimerization and a first application in asymmetric hydrosilylation
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A novel and efficient, two-step route to axially chiral biaryls is demonstrated. In a direct asymmetric cross-cyclotrimerization in the presence of a chiral cobalt(I) catalyst, axially chiral biaryls bearing phosphoryl moieties have been prepared, and through indirect evidence the authors have been able to clarify the origin of the stereochemical induction and the nature of the central intermediate in the catalytic cycle. By subsequent reduction of the phosphoryl moiety to the corresponding phosphine, a very efficient and atom-economical approach to chiral systems has been developed. These chiral systems clearly have great potential use as axially chiral monodentate P- or bidentate P,O-ligands, as has been demonstrated by the employment of the novel NAPHEP as a new monodentate acting ligand in an asymmetric hydrosilylation reaction.
- Heller, Barbara,Gutnov, Andrey,Fischer, Christine,Drexler, Hans-Joachim,Spannenberg, Anke,Redkin, Dmitry,Sundermann, Corinna,Sundermann, Bernd
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p. 1117 - 1128
(2007/10/03)
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- Biocatalytic asymmetric hydrogen transfer employing Rhodococcus ruber DSM 44541
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Nonracemic sec-alcohols of opposite absolute configuration were obtained either by asymmetric reduction of the corresponding ketone using 2-propanol as hydrogen donor or by enantioselective oxidation through kinetic resolution of the rac-alcohol using acetone as hydrogen acceptor employing whole lyophilized cells of Rhodococcus ruber DSM 44541. The microbial oxidation/reduction system exhibits not only excellent stereo- and enantioselectivity but also a broad substrate spectrum. Due to the exceptional tolerance of the biocatalyst toward elevated concentrations of organic materials (solvents, substrates and cosubstrates), the process is highly efficient. The simple preparation of the biocatalyst and its ease of handling turns this system into a versatile tool for organic synthesis.
- Stampfer, Wolfgang,Kosjek, Birgit,Faber, Kurt,Kroutil, Wolfgang
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p. 402 - 406
(2007/10/03)
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- New chiral hosts derived from dimeric tartaric acid: Efficient optical resolution of aliphatic alcohols by inclusion complexation
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The novel, chiral, host compounds 8 and 9 were derived from tartaric acid. Inclusion complexation with these host compounds permitted highly efficient resolution of some aliphatic alcohols (10-13). The symmetrical dimer host compound 8 is effective for optical resolution of alcohols 10, 12, and 13 by a combination of enantioselective inclusion complexation and distillation techniques. The unsymmetrical dimer host compound 9 is effective for optical resolution of cyanohydrin 11. The crystal structures of the inclusion complexes were analyzed by X-ray diffraction methods in order to elucidate the mechanism of the efficient chiral recognition in the inclusion crystals.
- Tanaka, Koichi,Honke, Shinji,Urbanczyk-Lipkowska, Zofia,Toda, Fumio
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p. 3171 - 3176
(2007/10/03)
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- Enzymatic resolution of alcohols via lipases immobilized in microemulsion-based gels
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Lipases immobilized in microemulsion-based gel (MBG) were used in the resolution of racemic alcohols, in a new, convenient method of catalysis in organic solvents which employs small amounts of the enzyme.
- De Jesus,Rezende,Nascimento
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- ORGANOSULPHUR COMPOUNDS XLVII ALKYLATION OF SULPHINIC ACIDS BY O-ALKYLISOUREAS: O-VERSUS S-REACTIVITY AND ASYMMETRIC SYNTHESIS OF ALKYL SULPHINATES
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The reaction of O-alkylisoureas with sulphinic acids was found to produce the corresponding sulphones and sulphinates, the latter being predominantly formed.The sulphinate to sulphone ratio is strongly influenced by the kind of alkyl groups in the O-alkylisourea and appeared to be also dependent on the solvent used.A few optically active sulphinates (e.e. up to 8.1percent) were prepared in the reaction between benzenesulphinic acid and a series of O-alkylisoureas bearing optically active substituents at the nitrogen atom.A possible reaction mechanism is discussed.
- Kielbasinski, Piotr,Zurawinski, Remigiusz,Drabowitz, Jozef,Mikolajczyk, Marian
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p. 6687 - 6692
(2007/10/02)
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- Stereochemistry of Aliphatic Carbocations, 14. Alkyl Shifts from Secondary to Primary Carbon Atoms
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Alkyl shifts from secondary to primary carbon atoms have been induced by the nitrous acid deamination of suitable amines (4, 22, 39, 51); they include sequential rearrangements (-CH3,CH3 and -CH3,H).Predominant although incomplete inversion at the migration origin has been observed (Me 70percent, Et 62-64percent, nPr 65percent, iPr 64percent, tBu 55percent).Our results require the intervention of open secondary carbocations which may be preceded by less stable bridged intermediates.
- Kirmse, Wolfgang,Guenther, Bernd-Rainer,Knist, Johannes,Kratz, Sigrid,Loosen, Karin,et al.
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p. 2127 - 2139
(2007/10/02)
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