- Asymmetric synthesis of amines by the reductive amination of ketones using (+) and (-) norepinephrine followed by periodate oxidation
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A new route for the synthesis of aralkyl primary amines is reported, where the commercially available (+) or (-) norepinephrine is condensed with aralkyl ketones followed by hydrogenation of the Schiff base using platinum catalyst. The chiral β-aminoalcohols thus obtained were oxidized by periodate to yield the aralkyl primary amines in 54-66% enantiomeric excess.
- Sreekumar,Pillai
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Read Online
- Ruthenium-catalysed asymmetric hydrosilylation of ketoximes using chiral oxazolinylferrocenylphosphines
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Chiral ruthenium(II) complexes, RuCl2(PPh3)(oxazolinylferrocenylphosphine), have been found to be effective catalysts for asymmetric hydrosilylation of ketoximes to give the corresponding primary amines in good yields with high enant
- Takei,Nishibayashi,Ishii,Mizobe,Uemura,Hidai
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Read Online
- Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase
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Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.
- Zhang, Jian-Dong,Chang, Ya-Wen,Dong, Rui,Yang, Xiao-Xiao,Gao, Li-Li,Li, Jing,Huang, Shuang-Ping,Guo, Xing-Mei,Zhang, Chao-Feng,Chang, Hong-Hong
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p. 124 - 128
(2020/09/21)
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- Generation of Oxidoreductases with Dual Alcohol Dehydrogenase and Amine Dehydrogenase Activity
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The l-lysine-?-dehydrogenase (LysEDH) from Geobacillus stearothermophilus naturally catalyzes the oxidative deamination of the ?-amino group of l-lysine. We previously engineered this enzyme to create amine dehydrogenase (AmDH) variants that possess a new hydrophobic cavity in their active site such that aromatic ketones can bind and be converted into α-chiral amines with excellent enantioselectivity. We also recently observed that LysEDH was capable of reducing aromatic aldehydes into primary alcohols. Herein, we harnessed the promiscuous alcohol dehydrogenase (ADH) activity of LysEDH to create new variants that exhibited enhanced catalytic activity for the reduction of substituted benzaldehydes and arylaliphatic aldehydes to primary alcohols. Notably, these novel engineered dehydrogenases also catalyzed the reductive amination of a variety of aldehydes and ketones with excellent enantioselectivity, thus exhibiting a dual AmDH/ADH activity. We envisioned that the catalytic bi-functionality of these enzymes could be applied for the direct conversion of alcohols into amines. As a proof-of-principle, we performed an unprecedented one-pot “hydrogen-borrowing” cascade to convert benzyl alcohol to benzylamine using a single enzyme. Conducting the same biocatalytic cascade in the presence of cofactor recycling enzymes (i.e., NADH-oxidase and formate dehydrogenase) increased the reaction yields. In summary, this work provides the first examples of enzymes showing “alcohol aminase” activity.
- Tseliou, Vasilis,Schilder, Don,Masman, Marcelo F.,Knaus, Tanja,Mutti, Francesco G.
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supporting information
p. 3315 - 3325
(2020/12/11)
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- Enzymatic Primary Amination of Benzylic and Allylic C(sp3)-H Bonds
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Aliphatic primary amines are prevalent in natural products, pharmaceuticals, and functional materials. While a plethora of processes are reported for their synthesis, methods that directly install a free amine group into C(sp3)-H bonds remain unprecedented. Here, we report a set of new-to-nature enzymes that catalyze the direct primary amination of C(sp3)-H bonds with excellent chemo-, regio-, and enantioselectivity, using a readily available hydroxylamine derivative as the nitrogen source. Directed evolution of genetically encoded cytochrome P411 enzymes (P450s whose Cys axial ligand to the heme iron has been replaced with Ser) generated variants that selectively functionalize benzylic and allylic C-H bonds, affording a broad scope of enantioenriched primary amines. This biocatalytic process is efficient and selective (up to 3930 TTN and 96percent ee), and can be performed on preparative scale.
- Jia, Zhi-Jun,Gao, Shilong,Arnold, Frances H.
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supporting information
p. 10279 - 10283
(2020/07/27)
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- Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases
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Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms fromNeosartoryaspp. (NfRedAm andNfisRedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as (R)-2-aminohexane in space time yields up to 8.1 g L?1h?1. The remarkable features ofNfRedAmand NfisRedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.
- Cosgrove, Sebastian C.,Grogan, Gideon,Mangas-Sanchez, Juan,Marshall, James R.,Palmer, Ryan B.,Ramsden, Jeremy I.,Sharma, Mahima,Thorpe, Thomas W.,Turner, Nicholas J.
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p. 5052 - 5057
(2020/06/09)
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- Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
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In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
- Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
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- Generation of amine dehydrogenases with increased catalytic performance and substrate scope from ε-deaminating L-Lysine dehydrogenase
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Amine dehydrogenases (AmDHs) catalyse the conversion of ketones into enantiomerically pure amines at the sole expense of ammonia and hydride source. Guided by structural information from computational models, we create AmDHs that can convert pharmaceutically relevant aromatic ketones with conversions up to quantitative and perfect chemical and optical purities. These AmDHs are created from an unconventional enzyme scaffold that apparently does not operate any asymmetric transformation in its natural reaction. Additionally, the best variant (LE-AmDH-v1) displays a unique substrate-dependent switch of enantioselectivity, affording S- or R-configured amine products with up to >99.9% enantiomeric excess. These findings are explained by in silico studies. LE-AmDH-v1 is highly thermostable (Tm of 69 °C), retains almost entirely its catalytic activity upon incubation up to 50 °C for several days, and operates preferentially at 50 °C and pH 9.0. This study also demonstrates that product inhibition can be a critical factor in AmDH-catalysed reductive amination.
- Tseliou, Vasilis,Knaus, Tanja,Masman, Marcelo F.,Corrado, Maria L.,Mutti, Francesco G.
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- Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines
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A library of 132 racemic chiral amines (α-substituted methylbenzylamines, benzhydrylamines, 1,2,3,4-tetrahydronaphthylamines (THNs), indanylamines, allylic and homoallylic amines, propargyl amines) was screened against the most versatile monoamine oxidase (MAO-N) variants D5, D9 and D11. MAO-N D9 exhibited the highest activity for most substrates and was applied to the deracemisation of a comprehensive set of selected primary amines. In all cases, excellent enantioselectivity was achieved (e.e. >99%) with moderate to good yields (55–80%). Conditions for the deracemisation of primary amines using a MAO-N/borane system were further optimised using THN as a template addressing substrate load, nature of the enzyme preparation, buffer systems, borane sources, and organic co-solvents.
- Herter, Susanne,Medina, Florian,Wagschal, Simon,Benha?m, Cyril,Leipold, Friedemann,Turner, Nicholas J.
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p. 1338 - 1346
(2017/10/06)
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- Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase
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The NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm) was combined with an NADPH oxidase (NOX) to develop a redox system that recycles the co-factor. The AspRedAm-NOX system was applied initially for the kinetic resolution of a variety of racemic secondary and primary amines to yield S-configured amines with enantiomeric excess (ee) values up to 99 %. The addition of ammonia borane to this system enabled the efficient deracemization of racemic amines, including the pharmaceutical drug rasagiline and the natural product salsolidine, with conversions up to >98 % and >99 % ee Furthermore, by using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype AspRedAm.
- Aleku, Godwin A.,Mangas-Sanchez, Juan,Citoler, Joan,France, Scott P.,Montgomery, Sarah L.,Heath, Rachel S.,Thompson, Matthew P.,Turner, Nicholas J.
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p. 515 - 519
(2018/02/15)
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- Enantioselective synthesis of amines via reductive amination with a dehydrogenase mutant from Exigobacterium sibiricum: Substrate scope, co-solvent tolerance and biocatalyst immobilization
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In recent years, the reductive amination of ketones in the presence of amine dehydrogenases emerged as an attractive synthetic strategy for the enantioselective preparation of amines starting from ketones, an ammonia source, a reducing reagent and a cofactor, which is recycled in situ by means of a second enzyme. Current challenges in this field consists of providing a broad synthetic platform as well as process development including enzyme immobilization. In this contribution these issues are addressed. Utilizing the amine dehydrogenase EsLeuDH-DM as a mutant of the leucine dehydrogenase from Exigobacterium sibiricum, a range of aryl-substituted ketones were tested as substrates revealing a broad substrate tolerance. Kinetics as well as inhibition effects were also studied and the suitability of this method for synthetic purpose was demonstrated with acetophenone as a model substrate. Even at an elevated substrate concentration of 50 mM, excellent conversion was achieved. In addition, the impact of water-miscible co-solvents was examined, and good activities were found when using DMSO of up to 30% (v/v). Furthermore, a successful immobilization of the EsLeuDH-DM was demonstrated utilizing a hydrophobic support and a support for covalent binding, respectively, as a carrier.
- L?we, Jana,Ingram, Aaron A.,Gr?ger, Harald
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p. 1387 - 1392
(2018/03/21)
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- Simultaneous engineering of an enzyme's entrance tunnel and active site: The case of monoamine oxidase MAO-N
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A new directed evolution approach is presented to enhance the activity of an enzyme and to manipulate stereoselectivity by focusing iterative saturation mutagenesis (ISM) simultaneously on residues lining the entrance tunnel and the binding pocket. This combined mutagenesis strategy was applied successfully to the monoamine oxidase from Aspergillus Niger (MAO-N) in the reaction of sterically demanding substrates which are of interest in the synthesis of chiral pharmaceuticals based on the benzo-piperidine scaffold. Reversal of enantioselectivity of Turner-type deracemization was achieved in the synthesis of (S)-1,2,3,4-tetrahydro-1-methyl-isoquinoline, (S)-1,2,3,4-tetrahydro-1-ethylisoquinoline and (S)-1,2,3,4-tetrahydro-1-isopropylisoquinoline. Extensive molecular dynamics simulations indicate that the altered catalytic profile is due to increased hydrophobicity of the entrance tunnel acting in concert with the altered shape of the binding pocket.
- Li, Guangyue,Yao, Peiyuan,Gong, Rui,Li, Jinlong,Liu, Pi,Lonsdale, Richard,Wu, Qiaqing,Lin, Jianping,Zhu, Dunming,Reetz, Manfred T.
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p. 4093 - 4099
(2017/07/10)
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- (R)- SELECTIVE AMINATION
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The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c] from the corresponding ketones of the general formula [1][a] by using novel transaminases. These novel transaminases are selected from two different groups: either from a group of some 20 proteins with sequences as specified herein, or from a group of proteins having transaminase activity and isolated from a microorganism selected from the group of organisms consisting of Rahnella aquatilis, Ochrobactrum anthropi, Ochrobactrum tritici, Sinorhizobium morelense, Curtobacterium pusiffium, Paecilomyces lilacinus, Microbacterium ginsengisoli, Microbacterium trichothecenolyticum, Pseudomonas citronellolis, Yersinia kristensenii, Achromobacter spanius, Achromobacter insolitus, Mycobacterium fortuitum, Mycobacterium frederiksbergense, Mycobacterium sacrum, Mycobacterium fluoranthenivorans, Burkhoideria sp., Burkhoideria tropica, Cosmospora episphaeria, and Fusarium oxysporum.
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Paragraph 0120; 0121; 0122
(2016/03/22)
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- A Single Lipase-Catalysed One-Pot Protocol Combining Aminolysis Resolution and Aza-Michael Addition: An Easy and Efficient Way to Synthesise β-Amino Acid Esters
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A novel one-pot protocol combining aza-Michael addition and aminolysis resolution was developed to obtain chiral β-amino acid esters with lipase B from Candida antarctica (CAL-B) as the only catalyst. This method is conducted under mild reaction conditions and is very easy to handle. After a series of detailed optimization studies, ten racemic aromatic or aliphatic amines were subjected to this one-pot procedure, and twelve chiral β-amino acid esters and ten chiral amides were successfully synthesised with excellent ee values in theoretical yields. Scaled-up procedures also worked without apparent reduction in reaction rate or enantioselectivity, which makes this method suitable for large-scale production of chiral β-amino acid esters. A one-pot protocol for simultaneous synthesis of chiral β-amino acid esters and amides was developed by combining single lipase B from Candida antarctica (CAL-B) catalysed aza-Michael addition and aminolysis resolution. This method requires mild reaction conditions and is very easy to handle. Chiral β-amino acid esters and chiral amides were obtained with excellent ee values and in theoretical yields.
- Xu, Fan,Wu, Qiongsi,Chen, Xiaoyang,Lin, Xianfu,Wu, Qi
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p. 5393 - 5401
(2015/08/24)
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- ω-Transaminases for the amination of functionalised cyclic ketones
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The potential of a number of enantiocomplementary ω-transaminases (ω-TAms) in the amination of cyclic ketones has been investigated. After a preliminary screening of several compounds with increasing complexity, different approaches to shift the equilibrium of the reaction to the amine products were studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2-propylamine as an amine donor was tolerated by all five selected ω-TAms, and therefore used in further experiments. Due to the higher conversions observed and interest in chiral amines studies then focused on the amination of α-tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the corresponding amine with at least one of the employed enzymes. Moreover, the amination of 2-methylcyclohexanone was investigated in more detail due to the different stereoselectivities observed with TAms used. The highest yields and stereoselectivities were obtained using the ω-TAm from Chromobacterium violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete stereoselectivity at the (1S)-amine position and up to 24 : 1 selectivity for the cis : trans [(1S,2R) : (1S,2S)] isomer.
- Richter,Simon,Lechner,Kroutil,Ward,Hailes
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p. 8843 - 8851
(2015/08/24)
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- Substrate profile of an ω-transaminase from Burkholderia vietnamiensis and its potential for the production of optically pure amines and unnatural amino acids
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A new (S)-enantioselective ω-transaminase (ω-TA) gene from Burkholderia vietnamiensis G4 was functionally expressed in Escherichia coli BL21 (DE3), and the purified recombinant N-terminal His-tagged ω-TA (HBV-ω-TA) had a dimeric structure with optimum pH and temperature of 8.4 and 40 C, respectively. The enzyme showed higher activities toward aromatic amines than aliphatic amines and (S)-1-methylbenzylamine ((S)-α-MBA) was the most active amino donor. For amino acceptor, keto acids, keto esters and aldehydes were more reactive than ketones with pyruvate ethyl ester being most active. Several chiral amines and unnatural amino acids or esters were synthesized using HBV-ω-TA as the catalyst and isopropylamine or (S)-α-MBA as amino donor. Notably, HBV-ω-TA catalyzed the amino transfer to β-keto esters to give optically pure β-amino acid esters. In addition, glyoxylate was used as amino acceptor for the first time in the kinetic resolution of racemic amines and optically pure amines, such as (R)-1-methylbenzylamine, (R)-1-phenylpropylamine, (R)-2-amino-4-phenylbutane and (R)-1-aminotetraline, were obtained.
- Jiang, Jinju,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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- Asymmetric amination of tetralone and chromanone derivatives employing ω-transaminases
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Various (S)-selective and (R)-selective ω-transaminases were investigated for the amination of 1- and 2-tetralone and derivatives as well as of 3- and 4-chromanone. All ketones tested were aminated to give the corresponding enantiopure amines (ee > 99%) employing at least one of the enzymes investigated. In most of the cases the (S)- as well as the (R)-enantiomer was obtained in optically pure form. The amination of 3-chromanone was performed on a 100 mg scale leading to optically pure (R)-3-aminochromane (ee > 99%) with complete conversion and 78% isolated yield.
- Pressnitz, Desiree,Fuchs, Christine S.,Sattler, Johann H.,Knaus, Tanja,Macheroux, Peter,Mutti, Francesco G.,Kroutil, Wolfgang
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p. 555 - 559
(2013/06/05)
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- Enantioselective reduction of ketoxime ethers with borane-oxazaborolidines and synthesis of the key intermediate leading to (S)-rivastigmine
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The reduction of representative alkyl aryl (E)-ketoxime O-benzyl ethers with borane catalyzed by terpene oxazaborolidines, derived from (1R)-nopinone and (1R)-camphor, gave the corresponding amines with 82-99% ee. Oxazaborolidines derived from (1S)-2-carene and (1S)-3-carene were less selective. (S)-1-(3-Methoxyphenyl)ethanamine (94% ee) the key intermediate in the synthesis of (S)-rivastigmine, was obtained by the reduction of (E)-1-(3-methoxyphenyl) ethanone O-benzyl oxime with borane/oxazaborolidine generated from (S)-valinol.
- Pakulski, Marcin M.,Mahato, Sanjit K.,Bosiak, Mariusz J.,Krzeminski, Marek P.,Zaidlewicz, Marek
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p. 716 - 721
(2012/09/21)
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- N-octanoyldimethylglycine trifluoroethyl ester, an acyl donor leading to highly enantioselective protease-catalysed kinetic resolution of amines
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The use of N-octanoyldimethylglycine trifluoroethyl ester as acyl donor in the kinetic resolution of aliphatic amines catalysed by proteases led to enantiomeric ratios >200 in most cases. The resolutions mediated by Protex 6L were shown to be much faster
- Queyroy, Severine,Vanthuyne, Nicolas,Gastaldi, Stephane,Bertrand, Michele P.,Gil, Gerard
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supporting information; experimental part
p. 1759 - 1764
(2012/08/08)
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- Stereoselectivity of four (R)-selective transaminases for the asymmetric amination of ketones
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Four (R)-ω-transaminases originating from Hyphomonas neptunium (HN-ωTA), Aspergillus terreus (AT-ωTA) and Arthrobacter sp. (ArR-ωTA), as well as an evolved transaminase (ArRmut11-ωTA) were successfully employed for the amination of prochiral ketones leading to optically pure (R)-amines. The first three transaminases displayed perfect stereoselectivity for the amination of all substrates tested (ee >99%). Furthermore, the transaminase AT-ωTA led in most cases to better conversion than ArR-ωTA and HN-ωTA using D-alanine as amine donor. α-Tetralone, which was the only substrate not accepted by HN-ωTA, ArR-ωTA, and AT-ωTA, was successfully transformed with perfect enantioselectivity (ee >99%) into the corresponding optically pure amine employing the variant ArRmut11-ωTA. Copyright
- Mutti, Francesco G.,Fuchs, Christine S.,Pressnitz, Desiree,Sattler, Johann H.,Kroutil, Wolfgang
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experimental part
p. 3227 - 3233
(2012/01/03)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-50
(2010/12/31)
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- BENZIMIDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
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Provided is an ORL-1 receptor agonist having improved bioavailability based on superior metabolic stability and strong and high selectivity, as compared to conventional compounds. A compound represented by the formula (I) wherein each symbol is as defined
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Page/Page column 16
(2009/12/23)
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- Nonenzymatic kinetic resolution of amines in ionic liquids
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Ionic liquids are remarkably suitable and clean media for performing nonenzymatic kinetic resolution (KR) of amines through enantioselective N-acetylation: high levels of selectivity were obtained with a large variety of amines at room temperature (up to s = 30). Georg Thieme Verlag Stuttgart.
- Sabot, Cyrille,Subhash, Pithani V.,Valleix, Alain,Arseniyadis, Stellios,Mioskowski, Charles
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p. 268 - 272
(2008/09/21)
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- Efficient diastereoselective intermolecular rhodium-catalyzed C-H amination
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(Chemical Equation Presented) Successful matchmaking: The combination of a chiral nitrene precursor with a chiral rhodium(II) catalyst is the key factor that allows efficient intermolecular regioselective C-H amination. Good-to-excellent yields and excellent diastereoselectivities can be obtained with a stoichiometric amount of the C-H bond containing substrate. nttl = N-1,8-naphthoyl-tert-leucine.
- Liang, Chungen,Robert-Peillard, Fabien,Fruit, Corinne,Mueller, Paul,Dodd, Robert H.,Dauban, Philippe
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p. 4641 - 4644
(2007/10/03)
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- Kinetic resolution of amines: A highly enantioselective and chemoselective acetylating agent with a unique solvent-induced reversal of stereoselectivity
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Solvents lend a hand: Changing the polarity of the reaction solvent from 1,3-dimethyltetrahydropyrimidin-2-one (DMPU) to toluene reverses the stereo-selectivity observed in the acetylation of amines with (1S,2S)-1 (see scheme). Optimizing the reaction conditions led to an unprecedented 90% ee (S) in DMPU at -20°C with a 33% conversion.
- Arseniyadis, Stellios,Valleix, Alain,Wagner, Alain,Mioskowski, Charles
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p. 3314 - 3317
(2007/10/03)
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- Comparison of the ω-transaminases from different microorganisms and application to production of chiral amines
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Microorganisms that are capable of (S)-enantioselective transamination of chiral amines were isolated from soil samples by selective enrichment using (S)-α-methylbenzylamine ((S)-α-MBA) as a sole nitrogen source. Among them, Klebsiella pneumoniae JS2F, Bacillus thuringiensis JS64, and Vibrio fluvialis JS17 showed good ω-transaminase (ω-TA) activities and the properties of the ω-TAs were investigated. The induction level of the enzyme was strongly dependent on the nitrogen source for the strains, except for V. fluvialis JS17. All the ω-TAs showed high enantioselectivity (E>50) toward (S)-α-MBA and broad amino donor specificities for arylic and aliphatic chiral amines. Besides pyruvate, aldehydes such as propionaldehyde and butyraldehyde showed good amino acceptor reactivities. All the ω-TAs showed substrate inhibition by (S)-α-MBA above 200 mM. Moreover, substrate inhibition by pyruvate above 10 mM was observed for ω-TA from V. fluvialis JS17. In the case of product inhibition, acetophenone showed much greater inhibitions than L-alanine for all ω-TAs. Comparison of the enzyme properties indicates that ω-transaminase from V. fluvialis JS17 is the best one for both kinetic resolution and asymmetric synthesis to produce enantiomerically pure chiral amines. Kinetic resolution of sec-butylamine (20 mM) was done under reduced pressure (150 Torr) to selectively remove an inhibitory product (2-butanone) using the enzyme from V. fluvialis JS17. Enantiomeric excess of (R)-sec-butylamine reached 94.7% after 12 h of reaction.
- Shin, Jong-Shik,Kim, Byung-Gee
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p. 1782 - 1788
(2007/10/03)
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- High-affinity, non-peptide agonists for the ORL1 (Orphanin FQ/nociceptin) receptor
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The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-napthalene-2-yl)-1- phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. The
- R?ver, Stephan,Adam, Geo,Cesura, Andrea M.,Galley, Guido,Jenck, Fran?ois,Monsma Jr., Frederick J.,Wichmann, Jürgen,Dautzenberg, Frank M.
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p. 1329 - 1338
(2007/10/03)
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- Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds
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The enantiomerically pure chiral benzocyclic amines 6-8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a-c. The method involves: (a) formation of chiral imines 10a-c from the prochiral ketones 9a-c and the inexpensive c
- Gutman, Arie L.,Etinger, Marina,Nisnevich, Gennady,Polyak, Felix
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p. 4369 - 4379
(2007/10/03)
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- Asymmetric Supported Reactions: Synthesis Of Chiral Amines
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Deracemization of amines, linked via Schiff bases to a chiral polyacrylic polymer has been studied.An enantiomeric excess of 72percent has been obtained with α-methyl benzylamine.
- Calmes, Monique,Daunis, Jacques,Hanouneh, Ahmad,Jacquier, Robert
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p. 817 - 820
(2007/10/02)
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- Aryloxypropanolaminotetralins, a process for their preparation and pharmaceutical compositions containing them
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Aryloxypropanolaminotetralins with beta-antagonist activity of the formula STR1 wherein R is hydrogen, hydroxy or methoxy and Ar is an optionally substituted aromatic or heteroaromatic group, in optically active or inactive form as well as their acid addition salts are described.A process for their preparation and pharmaceutical compositions containing the compounds of formula (i) or their pharmaceutically acceptable acid addition salts, are also described.
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- Asymmetric Reduction of Ketoxime O-Alkyl Ethers with Chirally Modified NaBH4-ZrCl4
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Reducing agents prepared from sodium borohydride (NaBH4), zirconium tetrachloride (ZrCl4), and chiral amino alcohols have been successfully applied to the enantioselective reduction of oxime ethers.Optically active primary amines were obtained in high enantiomeric excess ( : : : .
- Itsuno, Shinichi,Sakurai, Yoshiki,Shimizu, Koji,Ito, Koichi
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p. 1859 - 1863
(2007/10/02)
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- Asymmetric Reduction of Ketoxime O-Alkyl Ethers with Sodium Borohydride-Lewis Acid
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Novel hydride agents formed by combining Lewis acids with sodium borohydride (NaBH4) reduce quantitatively ketoxime O-alkyl ethers to the corresponding optically active primary amines with high enantioselectivities (up to 95percent e.e.) in the presence of chiral amino alcohols.
- Itsuno, Shinichi,Sakurai, Yoshiki,Shimizu, Koji,Ito, Koichi
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p. 1548 - 1549
(2007/10/02)
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- Stereoisomers of Allenic Amines as Inactivators of Monoamine Oxidase Type B. Stereochemical Probes of the Active Site
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The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary α-allenic amines have been investigated in detail.The chirality of the allene group in N-methyl-N-aralkylpenta-2,3-dienamines was found to have a profound effect on the inactivation rate, with the (R)-allenes being up to 200-fold more potent than their (S)-allenic counterparts.The ability of (S)-allenes to inactivate MAO was severely compromised by the presence of N-phenethyl or N-α-substituted-aralkyl substituents.The opposing chiralities in both the allene and aralkyl groups of (R,R)- and (S,S)-N-methyl-N-(1,2,3,4-tetrahydro-1-naphthyl)-penta-2,3-dieneamine resulted in a difference of more than 3 oredrs of magnitude in inactivation rates.The stereoselectivity of MAO-B was examined further with a series of reversible aralkylamine inhibitors; thus (R)-1,2,3,4-tetrahydro-1-naphthylamine was determined to be 150-fold more potent than its enantiomer.
- Smith, Roger A.,White, Robert L.,Krantz, Allen
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p. 1558 - 1566
(2007/10/02)
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- Ureidotetralin compounds
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This invention relates to ureidotetralin compounds and derivatives and selected enantiomers thereof. This invention also relates to methods for the preparation of said compounds which are useful as animal growth regulators and/or herbicidal agents.
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- Compositions and method of using ureidotetralin compounds or derivatives thereof
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This invention relates to a method for enhancing the growth rate of animals, particularly farm animals such as livestock, by administering to said animals compositions containing a growth-enhancing amount of a ureidotetralin compound or derivative thereof.
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