- Synthesis and reactivity towards carbon monoxide of an optically active endo five-membered ortho-cyclopalladated imine: X-ray molecular structure of trans-(μ-Cl)2[Pd(κ2-C,N-(R)-C6H4-CH{double bond, long}N-CHMe-Ph)]2
-
(R)-1-Phenylethyl-benzylidene-amine (1) reacted with Pd(OAc)2 in acetic acid at 60 °C under nitrogen affording the acetato-bridged dinuclear endo five-membered ortho-cyclopalladated compound (μ-OAc)2[Pd(κ2-C,N-(R)-C6H4-CH{double bond, long}N-CHMe-Ph)]2 (2) in 65% yield. Compound 2 was converted by a metathesis reaction with LiCl into the corresponding chloro-bridged dinuclear cyclopalladated compound (μ-Cl)2[Pd(κ2-C,N-(R)-C6H4-CH{double bond, long}N-CHMe-Ph)]2 (3). 1H NMR of CDCl3 solutions of compounds 2 and 3 treated separately with py-d5, (R)-1-phenylethylamine and racemic 1-phenylethylamine were consistent with the endo cyclopalladated structure and the R absolute configuration of the chiral carbon atoms of compounds 2 and 3. Compounds 2 and 3 reacted with carbon monoxide in methanol affording, as major compounds, methyl 2-formylbenzoate (91% chemical yield) and the epimers of 3-methoxy-2-[(R)-1-phenylethyl]isoindolin-1-one (64% chemical yield) in ca. 20% diastereomeric excess, respectively. The trans isomer of compound 3 crystallized in the P21 monoclinic space group with a = 10.430(4) A?, b = 12.082(8) A?, c = 11.168(4) A? and β = 95.20(3)° and presented C-H?Cl intramolecular and C-H?Pd intermolecular non-conventional hydrogen bonds.
- Albert, Joan,D'Andrea, Luci?a,Granell, Jaume,Tavera, Raquel,Font-Bardia, Mercè,Solans, Xavier
-
-
Read Online
- Crystallization-based resolution of 1,4-benzodioxane-2-carboxylic acid enantiomers via diastereomeric 1-phenylethylamides
-
Unlike the diastereomeric 1-phenylethylammonium salts, the diastereomeric N-1-phenylethylamides of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid show significant differences in fusibility and solubility so as to be efficiently resolved by precipitation of the less soluble diastereomer (>98% de), while chromatographic purification of the unprecipitated fraction affords the more soluble one (>99% de). Overall, 95% of the former and 80% of the latter are recovered. The hydrolysis of the two resolved amides provides the two acid enantiomers and the resolving amine in quantitative yield and with unchanged stereoisomeric purity.
- Fumagalli, Laura,Bolchi, Cristiano,Bavo, Francesco,Pallavicini, Marco
-
-
Read Online
- Determination of absolute configurations of amines and amino acids using nonchiral derivatizing agents (NCDA) and deuterium NMR.
-
Enantiomeric analysis and empirical determination of the absolute configuration of amines and amino acids can be easily performed using acetyl-d(3) chloride as a nonchiral derivatizing agent (deuterium probe) and deuterium NMR in a chiral solvent (Courtieu's method). In the case of amino acids, derivatization to amido esters, performed with methanol-d(4) and acetyl-d(3) chloride, gives a double opportunity for enantiomeric analysis.
- Chalard,Bertrand,Canet,Thery,Remuson,Jeminet
-
-
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
-
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
-
p. 124 - 128
(2020/09/21)
-
- Artificial plant cell walls as multi-catalyst systems for enzymatic cooperative asymmetric catalysis in non-aqueous media
-
The assembly of cellulose-based artificial plant cell wall (APCW) structures that contain different types of catalysts is a powerful strategy for the development of cascade reactions. Here we disclose an APCW catalytic system containing a lipase enzyme and nanopalladium particles that transform a racemic amine into the corresponding enantiomerically pure amide in high yieldviaa dynamic kinetic resolution.
- B?ckvall, Jan-E.,Córdova, Armando,Deiana, Luca,Naidu, Veluru Ramesh,Rafi, Abdolrahim A.,Tai, Cheuk-Wai
-
supporting information
p. 8814 - 8817
(2021/09/07)
-
- Method for recycling perindopril intermediate resolving agent (R)-(+)-alpha-phenylethylamine
-
The invention discloses a method for recycling and reusing a perindopril intermediate resolving agent (R)-(+)-alpha-phenylethylamine. The method comprises the following steps: S1, heating the free mother liquor to 30-45 DEG C, dropwise adding inorganic alkali to adjust the pH to be alkaline, adding an organic solvent A to extract twice, combining organic layers, controlling the temperature to be less than or equal to 50 DEG C for desolventizing under reduced pressure, and re-dissolving the distilled mother liquor in an organic solvent B; s2, cooling the distillation mother liquor to be less than or equal to 10 DEG C, dropwise adding inorganic acid to adjust the pH to be alkalescent, crystallizing, carrying out suction filtration, and filtering and washing with an organic solvent B to obtain a wet product; s3, dissolving the wet product in drinking water, heating the product to 30-45 DEG C, dropwise adding inorganic alkali to adjust the pH to be alkaline, and adding an organic solvent A for extraction. The method is different from a conventional chiral amine recovery method of alkaline extraction and reduced evaporation, an improved method of alkaline extraction, desolvation, acid crystallization, alkaline extraction and reduced evaporation is adopted, the process stability is high, and the obtained recovered (R)-(+)-alpha-phenylethylamine is colorless and transparent in appearance, high in purity, good in application effect and large in cycle index.
- -
-
Paragraph 0045-0048
(2021/07/10)
-
- Generation of Oxidoreductases with Dual Alcohol Dehydrogenase and Amine Dehydrogenase Activity
-
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.
-
supporting information
p. 3315 - 3325
(2020/12/11)
-
- Biochemical and Structural Characterization of an (R)-Selective Transaminase in the Asymmetric Synthesis of Chiral Hydroxy Amines
-
An (R)-selective transaminase RbTA with excellent stereoselectivity (>99% ee) in the asymmetric amination of hydroxy ketones was identified. Biochemical characterization showed that RbTA exhibited the highest activity toward 4-hydroxy-2-butanone among reported enzymes, and that it has broad substrate specificity, including for aliphatic, aromatic, and alicyclic ketones. Crystallization of RbTA were performed, as were molecular docking and mutagenesis studies. Residue Tyr125 plays a key role in substrate recognition by forming a hydrogen bond with hydroxy ketone. The applicability of the enzyme was determined in preparative-scale synthesis of (R)-3-amino-1-butanol, demonstrating the potential of RbTA as a green biocatalyst for production of value-added chiral hydroxy amines. This study provides an efficient tool for enzymatic synthesis of chiral hydroxy amines, as well as structural insight into substrate recognition by transaminases in the asymmetric amination of hydroxy ketones. (Figure presented.).
- Li, Fulong,Liang, Youxiang,Wei, Yuwen,Zheng, Yukun,Du, Yan,Yu, Huimin
-
supporting information
p. 4582 - 4589
(2021/08/07)
-
- Iterative Alanine Scanning Mutagenesis Confers Aromatic Ketone Specificity and Activity of L-Amine Dehydrogenases
-
Direct reductive amination of prochiral ketones catalyzed by amine dehydrogenases is attractive in the synthesis of active pharmaceutical ingredients. Here, we report the protein engineering of L-Bacillus cereus amine dehydrogenase to allow reactivity on synthetically useful aromatic ketone substrates using an iterative, multiple-site alanine scanning mutagenesis approach. Mutagenesis libraries based on molecular docking, iterative alanine scanning, and double-proximity filter approach significantly expand the scope of active pharmaceutical ingredients relevant building blocks. The eventual quintuple mutant (A115G/T136A/L42A/V296A/V293A) showed reactivity toward aromatic ketones 12 a (5-phenyl-pentan-2-one) and 13 a (6-phenyl-hexan-2-one), which have not been reported to serve as targets of reductive amination by currently available amine dehydrogenases. Docking simulation and tunnel analysis provided valuable insights into the source of the acquired specificity and activity.
- Mu, Xiaoqing,Wu, Tao,Mao, Yong,Zhao, Yilei,Xu, Yan,Nie, Yao
-
p. 5243 - 5253
(2021/11/16)
-
- Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
-
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
- Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
-
supporting information
p. 390 - 398
(2021/01/13)
-
- Rational Design of Chiral Nanohelices from Self-Assembly of Meso-tetrakis (4-Carboxyphenyl) Porphyrin-Amino Acid Conjugates
-
In this article, meso-tetrakis (4-carboxyphenyl) porphyrins modified with different amino acids were designed, synthesized, and researched. The chiral self-assembly behavior of these porphyrin-amino acid molecules can be precisely controlled by adjusting the pH, constituent amino acids, and temperature, thereby giving rise to chiral nanostructures with precisely tailored helical pitch and handedness. This research provides a certain reference for the design and preparation of chiral nanomaterials and has potential application prospects in chiral resolution and chiral catalysis.
- Yang, Xuejiao,Shen, Yuhe,Liu, Jiayu,Wang, Yuefei,Qi, Wei,Su, Rongxin,He, Zhimin
-
p. 13067 - 13074
(2021/11/16)
-
- An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions
-
Asymmetric reductive amination (ARA) is one of the most promising methods for the synthesis of chiral amines. Herein we report our efforts on merging two ARA reactions into a single-step transformation. Catalyzed by a complex formed from iridium and a steric hindered phosphoramidite, readily available and inexpensive aromatic ketones initially undergo the first ARA with ammonium acetate to afford primary amines, which serve as the amine sources for the second ARA, and finally provide the enantiopure C2-symmetric secondary amine products. The developed process competently enables the successive coupling of inorganic and organic nitrogen sources with ketones in the same reaction system. The Br?nsted acid additive plays multiple roles in this procedure: it accelerates the formation of imine intermediates, minimizes the inhibitory effect of N-containing species on the iridium catalyst, and reduces the primary amine side products.
- Chang, Mingxin,Gao, Zhaofeng,Geng, Huiling,Huang, Haizhou,Liu, Jingwen
-
supporting information
p. 27307 - 27311
(2021/11/17)
-
- Transaminase Engineering and Process Development for a Whole-Cell Neat Organic Process to Produce (R)-α-Phenylethylamine
-
The production of (R)-α-phenylethylamine ((R)-α-PEA) from acetophenone is a classic reaction for the characterization of transaminases. However, developing a commercially viable transaminase process to manufacture (R)-α-PEA usually suffers from two drawbacks. One is related to the biocatalyst itself, since transaminases are easily inhibited by (R)-α-PEA at low concentrations. The other drawback is a common low space-time yield of typical transaminase processes, because the reaction equilibrium greatly favors the formation of acetophenone(R)-α-PEA. In this study, an (R)-selective amine transaminase (TA) from Aspergillus fumigatus Af293 was engineered by a directed evolution for an efficient process to produce (R)-α-PEA. The evolved variant showed an3000-fold increase in activity and a tolerance with 2.0 M isopropylamine as well as the complete absence of inhibition by (R)-α-PEA. At the same time, using this evolved TA variant, a continuous neat organic process using whole-cells was developed where the biocatalyst and remaining acetophenone can be efficiently separated from (R)-α-PEA and reused repetitively. This not only decreases the overall cost and waste generation but also achieves a very high space-time yield of up to 168 g L-1 d-1 of (R)-α-PEA in an industrial pilot scale setup.
- Bocola, Marco,Bong, Yong Koy,Cai, Baoqin,Chen, Haibin,Daussmann, Thomas,He, Kuifang,Hong, Ruimei,Hu, Hu,Ji, Yaoyao,Liu, Sitong,Luo, Xiao,Peng, Qinli,Shang, Chuanyang,Sun, Lei,Wang, Jiyong,Wang, Juanjuan,Wang, Zikun,Yang, Zhuhong,Zhang, Chengxiao,Zhou, Ameng,Zhu, Ying
-
-
- Enantioselective Bioamination of Aromatic Alkanes Using Ammonia: A Multienzymatic Cascade Approach
-
Chiral amines are common drug building blocks and important active pharmaceutical ingredients. Preparing these functionalized compounds from simple materials, such as alkanes, is of great interest. We recently developed an artificial bioamination cascade for the C?H amination of cyclic alkanes by combining P450 monooxygenase, alcohol dehydrogenase, and amine dehydrogenase. Herein, this system has been extended to the synthesis of chiral aromatic amines. In the first hydroxylation step, process optimization increased the conversion to 77 %. Two stereoselectively complementary alcohol dehydrogenases and an amine dehydrogenase were selected for the bioconversion of aromatic hydrocarbons to amines. The amination reaction was optimized with respect to cofactor addition and enzyme dosage. Isopropanol was added to decrease ketone intermediate accumulation in the amination step, which further enhanced the overall conversion. This cascade system converted a panel of hydrocarbon substrates into the corresponding amines with excellent optical purity (>99 % ee) and moderate conversion ratios (13–53 %).
- Chen, Fei-Fei,Wang, Hui,Xu, Jian-He,Yu, Hui-Lei,Zheng, Yu-Cong
-
-
- Parallel interconnected kinetic asymmetric transformation (PIKAT) with an immobilized ω-transaminase in neat organic solvent
-
Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.
- B?hmer, Wesley,Koenekoop, Lucien,Mutti, Francesco G.,Simon, Timothée
-
-
- Enzymatic Primary Amination of Benzylic and Allylic C(sp3)-H Bonds
-
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.
-
supporting information
p. 10279 - 10283
(2020/07/27)
-
- Development of a new synthesis approach for S-pregabalin by optimizing the preparation stages
-
In the present study, we aimed to optimize the synthesis stages of S-pregabalin ((S)-3-(aminomethyl)-5-methylhexanoic acid), a well-known anticonvulsant drug. We used appropriate solvents and compounds to reach a straightforward and applicable method. The advantages of this research were avoiding use of expensive and environment pollutant reagents and solvents, and also using a recoverable reagent. Discarding prevention of the intermediates and reagents besides attaining a higher yield of the obtained product were the additional achievements. All structures were characterized by FT-IR, 1H NMR, and the purity of S-pregabalin was evaluated using the HPLC assay.
- Mansoori, Arsalan,Zahednezhad, Fahimeh,Bavili Tabrizi, Ahad,Shahbazi Mojarrad, Javid
-
-
- Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen
-
The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 percent yield and 74 percent ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)-f-binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user-friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 percent achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.
- Ernst, Martin,Ghosh, Tamal,Hashmi, A. Stephen K.,Schaub, Thomas
-
supporting information
(2020/07/14)
-
- Asymmetric Synthesis of Primary and Secondary β-Fluoro-arylamines using Reductive Aminases from Fungi
-
The synthesis of chiral amines is of central importance to pharmaceutical chemistry, and the inclusion of fluorine atoms in drug molecules can both increase potency and slow metabolism. Optically enriched β-fluoroamines can be obtained by the kinetic resolution of racemic amines using amine transaminases (ATAs), but yields are limited to 50 %, and also secondary amines are not accessible. In order to overcome these limitations, we have applied NADPH-dependent reductive aminase enzymes (RedAms) from fungal species to the reductive amination of α-fluoroacetophenones with ammonia, methylamine and allylamine as donors, to yield β-fluoro primary or secondary amines with >90 % conversion and between 85 and 99 % ee. In addition, the effect of the progressive introduction of fluorine atoms to the α-position of the acetophenone substrate reveals the effect of mono-, di- and tri-fluorination on the proportion of amine and alcohol in product mixtures, shedding light on the promiscuous ability of imine reductase (IRED)-type dehydrogenases to reduce fluorinated acetophenones to alcohols.
- González-Martínez, Daniel,Cuetos, Aníbal,Sharma, Mahima,García-Ramos, Marina,Lavandera, Iván,Gotor-Fernández, Vicente,Grogan, Gideon
-
p. 2421 - 2425
(2020/03/25)
-
- Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases
-
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.
-
p. 5052 - 5057
(2020/06/09)
-
- Stereochemical analysis of chiral amines, diamines, and amino alcohols: Practical chiroptical sensing based on dynamic covalent chemistry
-
Practical chiroptical sensing with a small group of commercially available aromatic aldehydes is demonstrated. Schiff base formation between the electron-deficient 2,4-dinitrobenzaldehyde probe and either primary amines, diamines, or amino alcohols proceeds smoothly in chloroform at room temperature and is completed in the presence of molecular sieves within 2.5 hours. The substrate binding coincides with a distinct circular dichroism signal induction at approximately 330 nm, which can be correlated to the absolute configuration and enantiomeric composition of the analyte. The usefulness of this sensing method is highlighted with the successful sensing of 18 aliphatic and aromatic amines and amino alcohols and five examples showing quantitative %ee determination with good accuracy.
- Hassan, Diandra S.,Thanzeel, F. Yushra,Wolf, Christian
-
supporting information
p. 457 - 463
(2020/02/15)
-
- Addition of Highly Polarized Organometallic Compounds to N-tert-Butanesulfinyl Imines in Deep Eutectic Solvents under Air: Preparation of Chiral Amines of Pharmaceutical Interest
-
Highly polarized organometallic compounds of s-block elements are added smoothly to chiral N-tert-butanesulfinyl imines in the biodegradable d-sorbitol/choline chloride eutectic mixture, thereby granting access to enantioenriched primary amines after quantitatively removing the sulfinyl group. The practicality of the method is further highlighted by proceeding at ambient temperature and under air, with very short reaction times (2 min), enabling the preparation of diastereoisomeric sulfinamides in very good yields (74–98 %) and with a broad substrate scope, and the possibility of scaling up the process. The method is demonstrated in the asymmetric syntheses of both the chiral amine side-chain of (R,R)-Formoterol (96 % ee) and the pharmaceutically relevant (R)-Cinacalcet (98 % ee).
- Capriati, Vito,Cicco, Luciana,García-álvarez, Joaquín,González-Sabín, Javier,Perna, Filippo M.,Ríos-Lombardía, Nicolás,Salomone, Antonio,Vitale, Paola
-
-
- Asymmetric Stepwise Reductive Amination of Sulfonamides, Sulfamates, and a Phosphinamide by Nickel Catalysis
-
Asymmetric reductive amination of poorly nucleophilic sulfonamides was realized in the presence of nickel catalysts and titanium alkoxide. A wide range of ketones, including enolizable ketones and some biaryl ones, were converted into sulfonamides in excellent enantiomeric excess. The cyclization of sulfamates and intermolecular reductive amination of a diarylphosphinamide were also successful. Formic acid was used as a safe and economic surrogate of high-pressure hydrogen gas.
- Zhao, Xiaohu,Xu, Haiyan,Huang, Xiaolei,Zhou, Jianrong Steve
-
p. 292 - 296
(2018/12/13)
-
- Preparation of chiral primary amine through asymmetric reductive amination of simple ketone under catalytic action of ruthenium-diphosphine catalyst
-
The invention relates to a method for preparing chiral primary amine. The method comprises the steps: performing a hydrogenation reductive amination reaction on simple ketone and an ammonium salt RCOONH4 under the action of a ruthenium-chiral diphosphine catalyst, then adding an acid, performing heating for hydrolysis, and adopting a one-pot method to prepare the chiral primary amine. The method has the advantages of good universality of the substrate, high reaction efficiency and the like.
- -
-
Paragraph 0060-0067
(2019/07/04)
-
- Deracemization of Racemic Amines to Enantiopure (R)- and (S)-amines by Biocatalytic Cascade Employing ω-Transaminase and Amine Dehydrogenase
-
A one-pot deracemization strategy for α-chiral amines is reported involving an enantioselective deamination to the corresponding ketone followed by a stereoselective amination by enantiocomplementary biocatalysts. Notably, this cascade employing a ω-transaminase and amine dehydrogenase enabled the access to both (R)-and (S)-amine products, just by controlling the directions of the reactions catalyzed by them. A wide range of (R)-and (S)-amines was obtained with excellent conversions (>80 %) and enantiomeric excess (>99 % ee). Finally, preparative scale syntheses led to obtain enantiopure (R)- and (S)-13 with the isolated yields of 53 and 75 %, respectively.
- Yoon, Sanghan,Patil, Mahesh D.,Sarak, Sharad,Jeon, Hyunwoo,Kim, Geon-Hee,Khobragade, Taresh P.,Sung, Sihyong,Yun, Hyungdon
-
p. 1898 - 1902
(2019/02/27)
-
- Method for synthesizing chiral amine compound
-
The present invention provides a method for synthesizing a chiral amine compound. The method comprises the following steps: (1) reacting a compound of formula I with t-butylsulfonamide in the presenceof a catalyst to obtain a compound having a structure represented by formula II; 2) reacting the compound of the formula II in a hydrogen atmosphere in the presence of an iridium catalyst and a ligand to obtain a compound of formula III; and (3) carrying out a t-butylsulfonyl group removal reaction on the compound of the formula III to obtain the chiral amine compound. The method constructs the structure of sulfonamide by a keto carbonylgroup, and synthesizes the chiral amine compound with the aralkylamine structure by an asymmetric catalytic hydrogenation reaction of the sulfonamide structure, the ee value is generally 80% or above, the highest ee value is 99% or above, the yield of each step reaction can reach 90% or above, and the total yield is high.
- -
-
-
- Nickel-Catalyzed Asymmetric Hydrogenation of N-Sulfonyl Imines
-
An efficient nickel-catalyzed asymmetric hydrogenation of N-tBu-sulfonyl imines was developed with excellent yields and enantioselectivities using (R,R)-QuinoxP* as a chiral ligand. The use of a much lower catalyst loading (0.0095 mol %, S/C=10500) represents the highest catalytic activity for the Ni-catalyzed asymmetric hydrogenations reported so far. Mechanistic studies suggest that a coordination equilibrium exists between the nickel salt and its complex, and that excess nickel salt promotes the formation of the active Ni-complex, and therefore improved the efficiency of the hydrogenation. The catalytic cycle was also investigated by calculations to determine the origin of the enantioselectivity. An extensive network of numerous weak attractive interactions was found to exist between the catalyst and substrate in the transition state and may also contribute to the high catalytic activity.
- Li, Bowen,Chen, Jianzhong,Zhang, Zhenfeng,Gridnev, Ilya D.,Zhang, Wanbin
-
supporting information
p. 7329 - 7334
(2019/05/01)
-
- Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
-
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
-
-
- Generation of amine dehydrogenases with increased catalytic performance and substrate scope from ε-deaminating L-Lysine dehydrogenase
-
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.
-
-
- Amine Transaminase from Exophiala Xenobiotica - Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones
-
Amine transaminases are frequently used for the production of chiral amines starting from prochiral ketones. These amines can be applied as active pharmaceutical ingredients or drug precursors. However, there are still limitations to the use of amine transaminases when it comes to bulky ketone substrates, such as biaryl ketones. Using data mining, an (R)-selective amine transaminase from Exophiala xenobiotica was identified which naturally converts biaryl ketone substrates to the corresponding amines with up to 85% conversion and excellent enantioselectivity (>99% ee). Its protein crystal structure was obtained with a resolution of 1.52 ?, which enabled us to explain this interesting substrate acceptance. Structure-guided protein engineering resulted in a quintuple variant with increased stability. Moreover, the amino acid exchange T273S increased the activity and broadened the substrate scope, enabling conversions of various biaryl ketones with up to >99%. A preparative biotransformation of 1-(4-(pyridin-3-yl)phenyl)ethenone at 75 mM (15 g/L) resulted in 96% of isolated yield of the respective amine.
- Telzerow, Aline,Paris, Juraj,H?kansson, Maria,González-Sabín, Javier,Ríos-Lombardía, Nicolás,Schürmann, Martin,Gr?ger, Harald,Morís, Francisco,Kourist, Robert,Schwab, Helmut,Steiner, Kerstin
-
p. 1140 - 1148
(2019/01/21)
-
- Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
-
ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.
- Han, Sang-Woo,Shin, Jong-Shik
-
p. 3287 - 3295
(2019/06/21)
-
- Decorated single-enantiomer phosphoramide-based silica/magnetic nanocomposites for direct enantioseparation
-
The nano-composites Fe3O4SiO2(-O3Si[(CH2)3NH])P(O)(NH-R(+)CH(CH3)(C6H5))2 (Fe3O4SiO2PTA(+)) and Fe3O4SiO2(-O3Si[(CH2)3NH])P(O)(NH-S(-)CH(CH3)(C6H5))2 (Fe3O4SiO2PTA(-)) were prepared and used for the chiral separation of five racemic mixtures (PTA = phosphoric triamide). The separation results show chiral recognition ability of these materials with respect to racemates belonging to different families of compounds (amine, acid, and amino-acid), which show their feasibility to be potential adsorbents in chiral separation. The nano-composites were characterized by FTIR, TEM, SEM, EDX, XRD, and VSM. The VSM curves of nano-composites indicate their superparamagnetic property, which is stable after their use in the separation process. Fe3O4, Fe3O4SiO2, Fe3O4SiO2PTA(+) and Fe3O4SiO2PTA(-) are regularly spherical with uniform shape and the average sizes of 17-20, 18-23, 36-47 and 43-52 nm, respectively.
- Karimi Ahmadabad, Fatemeh,Pourayoubi, Mehrdad,Bakhshi, Hadi
-
p. 27147 - 27156
(2019/09/12)
-
- Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2
-
A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.
- Tan, Xuefeng,Gao, Shuang,Zeng, Weijun,Xin, Shan,Yin, Qin,Zhang, Xumu
-
supporting information
p. 2024 - 2027
(2018/02/19)
-
- METHOD FOR THE HOMOGENEOUS CATALYTIC REDUCTIVE AMINATION OF CARBONYL COMPOUNDS
-
The present invention relates to a method for the reductive amination of a carbonyl compound, comprising one or more carbonyl groups amenable to reductive amination, forming the corresponding primary amine, characterized in that the reaction is carried out in the presence of a homogeneously dissolved catalyst complex K, comprising at least one metal atom from Group 8, 9 or 10 of the periodic table, bearing a bidentate phosphane ligand, a carbonyl ligand, a neutral ligand and a hydride ligand, and also an acid as co-catalyst.
- -
-
Paragraph 0212; 0222-0223; 0224; 0225-0226
(2018/07/29)
-
- A Practical Electrophilic Nitrogen Source for the Synthesis of Chiral Primary Amines by Copper-Catalyzed Hydroamination
-
A mild and practical method for the catalytic installation of the amino group across alkenes and alkynes has long been recognized as a significant challenge in synthetic chemistry. As the direct hydroamination of olefins using ammonia requires harsh conditions, the development of suitable electrophilic aminating reagents for formal hydroamination methods is of importance. Herein, we describe the use of 1,2-benzisoxazole as a practical electrophilic primary amine source. Using this heterocycle as a new amino group delivery agent, a mild and general protocol for the copper-hydride-catalyzed hydroamination of alkenes and alkynes to form primary amines was developed. This method provides access to a broad range of chiral α-branched primary amines and linear primary amines, as demonstrated by the efficient synthesis of the antiretroviral drug maraviroc and the formal synthesis of several other pharmaceutical agents.
- Guo, Sheng,Yang, Jeffrey C.,Buchwald, Stephen L.
-
supporting information
p. 15976 - 15984
(2018/11/23)
-
- n-Butylamine as an alternative amine donor for the stereoselective biocatalytic transamination of ketones
-
Formal reductive amination has been a main focus of biocatalysis research in recent times. Among the enzymes able to perform this transformation, pyridoxal-5′-phosphate-dependent transaminases have shown the greatest promise in terms of extensive substrate scope and industrial application. Despite concerted research efforts in this area, there exist relatively few options regarding efficient amino donor co-substrates capable of allowing high conversion and atom efficiency with stable enzyme systems. Herein we describe the implementation of the recently described spuC gene, coding for a putrescine transaminase, exploiting its unusual amine donor tolerance to allow use of inexpensive and readily-available n-butylamine as an alternative to traditional methods. Via the integration of SpuC homologues with tandem co-product removal and cofactor regeneration enzymes, high conversion could be achieved with just 1.5 equivalents of the amine with products displaying excellent enantiopurity.
- Slabu, Iustina,Galman, James L.,Iglesias, Cesar,Weise, Nicholas J.,Lloyd, Richard C.,Turner, Nicholas J.
-
-
- Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding, Control of Selectivity, and Chirality Sensing with a Single System
-
Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central-to-axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.
- Ni, Cailing,Zha, Daijun,Ye, Hebo,Hai, Yu,Zhou, Yuntao,Anslyn, Eric V.,You, Lei
-
supporting information
p. 1300 - 1305
(2018/01/27)
-
- Enantioselective synthesis of amines via reductive amination with a dehydrogenase mutant from Exigobacterium sibiricum: Substrate scope, co-solvent tolerance and biocatalyst immobilization
-
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
-
p. 1387 - 1392
(2018/03/21)
-
- Asymmetric Synthesis of 1-Phenylethylamine from Styrene via Combined Wacker Oxidation and Enzymatic Reductive Amination
-
An enantioselective chemoenzymatic two-step one-pot transformation of styrene to 1-phenylethylamine has been developed based on combining an initial Pd/Cu-catalyzed Wacker oxidation of styrene with a subsequent reductive amination of the in situ formed acetophenone. As a nitrogen source only ammonia is needed. The incompatible catalysts were separated by means of a polydimethylsiloxane membrane, thus leading to quantitative conversion and an excellent enantiomeric excess of the corresponding amine. The overall one-pot process formally corresponds to an asymmetric hydroamination of styrene with ammonia.
- Uthoff, Florian,Gr?ger, Harald
-
p. 9517 - 9521
(2018/08/01)
-
- Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines
-
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.
-
p. 1338 - 1346
(2017/10/06)
-
- Chiral Organic Cages with a Triple-Stranded Helical Structure Derived from Helicene
-
We report the use of helicene with an intrinsic helical molecular structure to prepare covalent organic cages via imine condensation. The organic cages revealed a [3+2]-type architecture containing a triple-stranded helical structure with three helicene units arranged in a propeller-like fashion with the framework integrally twisted. Such structural chirality was retained upon dissolution in organic solvents, as indicated by a strong diastereotopy effect in proton NMR and unique Cotton effects in circular dichroism spectra. Further study on chiral adsorption showed that the chiral organic cages possess considerable enantioselectivity toward a series of aromatic racemates.
- Malik, Abaid Ullah,Gan, Fuwei,Shen, Chengshuo,Yu, Na,Wang, Ruibin,Crassous, Jeanne,Shu, Mouhai,Qiu, Huibin
-
supporting information
p. 2769 - 2772
(2018/03/08)
-
- Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
-
A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
- Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
-
p. 1067 - 1078
(2018/08/01)
-
- Biocatalytic transamination with near-stoichiometric inexpensive amine donors mediated by bifunctional mono- and di-amine transaminases
-
The discovery and characterisation of enzymes with both monoamine and diamine transaminase activity is reported, allowing conversion of a wide range of target ketone substrates with just a small excess of amine donor. The diamine co-substrates (putrescine, cadaverine or spermidine) are bio-derived and the enzyme system results in very little waste, making it a greener strategy for the production of valuable amine fine chemicals and pharmaceuticals.
- Galman, James L.,Slabu, Iustina,Weise, Nicholas J.,Iglesias, Cesar,Parmeggiani, Fabio,Lloyd, Richard C.,Turner, Nicholas J.
-
supporting information
p. 361 - 366
(2017/08/14)
-
- Two-Enzyme Hydrogen-Borrowing Amination of Alcohols Enabled by a Cofactor-Switched Alcohol Dehydrogenase
-
The NADPH-dependent secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (TeSADH), displaying broad substrate specificity and low enantioselectivity, was engineered to accept NADH as a cofactor. The engineered TeSADH showed a >10 000-fold switch from NADPH towards NADH compared to the wildtype enzyme. This TeSADH variant was applied to a biocatalytic hydrogen-borrowing system that employed catalytic amounts of NAD+, ammonia, and an amine dehydrogenase, which thereby enabled the conversion a range of alcohols into chiral amines.
- Thompson, Matthew P.,Turner, Nicholas J.
-
p. 3833 - 3836
(2017/09/25)
-
- Co-immobilized Phosphorylated Cofactors and Enzymes as Self-Sufficient Heterogeneous Biocatalysts for Chemical Processes
-
Enzyme cofactors play a major role in biocatalysis, as many enzymes require them to catalyze highly valuable reactions in organic synthesis. However, the cofactor recycling is often a hurdle to implement enzymes at the industrial level. The fabrication of heterogeneous biocatalysts co-immobilizing phosphorylated cofactors (PLP, FAD+, and NAD+) and enzymes onto the same solid material is reported to perform chemical reactions without exogeneous addition of cofactors in aqueous media. In these self-sufficient heterogeneous biocatalysts, the immobilized enzymes are catalytically active and the immobilized cofactors catalytically available and retained into the solid phase for several reaction cycles. Finally, we have applied a NAD+-dependent heterogeneous biocatalyst to continuous flow asymmetric reduction of prochiral ketones, thus demonstrating the robustness of this approach for large scale biotransformations.
- Velasco-Lozano, Susana,Benítez-Mateos, Ana I.,López-Gallego, Fernando
-
supporting information
p. 771 - 775
(2017/01/13)
-
- A right-handed phenethylamine salt and a right the preparation method of the phenethylamine
-
The invention provides a preparation method for R-(+)-alpha-phenylethylamine salt and R-(+)-alpha-phenylethylamine. The preparation method comprises a step of subjecting DL-alpha-phenylethylamine and a resolving agent to a salt formation reaction in a reaction solvent, wherein the resolving agent is one selected from the group consisting of N-p-nitrobenzoyl-L-glutamic acid, L-glutamic acid and gulonic acid, the reaction solvent is one or more selected from the group consisting of acetone and ethanol, the salt formation reaction is to add the resolving agent into the reaction solvent, then add DL-alpha-phenylethylamine and carry out the reaction, DL-alpha-phenylethylamine is added drop by drop for 20 to 40 min, the ethanol is 95% ethanol, and a ratio of the volume of the reaction solvent to the mass of DL-alpha-phenylethylamine is 2-8: 1, preferably 3-5: 1. The method is finished in only one step, does not need refining, produces little waste water, has high yield, enables high-optical purity R-(+)-alpha-phenylethylamine salt and R-(+)-alpha-phenylethylamine to be obtained, uses commercially available reagents and raw materials and is applicable to industrialization.
- -
-
-
- Enantioselective precipitate of amines, amino alcohols, and amino acids via schiff base reaction in the presence of chiral ionic liquid
-
Two novel chiral ionic liquids are synthesized as the chiral selector. Racemates of amines, amino alcohols, and amino acids could generate enantioselective precipitate with multicomponent self-assemblies under mild conditions. The approach allows for enan
- Wu, Datong,Cai, Pengfei,Zhao, Xiaoyong,Pan, Yuanjiang
-
p. 5018 - 5021
(2017/11/06)
-
- Asymmetric catalysis of the carbonyl-amine condensation: Kinetic resolution of primary amines
-
A Br?nsted acid catalyzed kinetic resolution of primary amines is described that is based on the condensation between an amine and a carbonyl compound. 1,3-Diketones react with racemic α-branched amines to furnish the corresponding enantioenriched enaminone and recovered starting material. Good to excellent enantioselectivity was observed with both aromatic and aliphatic primary amines. This process represents the first small-molecule catalyzed kinetic resolution of aliphatic amines.
- Das, Sayantani,Majumdar, Nilanjana,De, Chandra Kanta,Kundu, Dipti Sankar,Dohring, Arno,Garczynski, Anika,List, Benjamin
-
supporting information
p. 1357 - 1359
(2017/02/10)
-
- Amine dehydrogenases: Efficient biocatalysts for the reductive amination of carbonyl compounds
-
Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study-operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme-performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the (R)-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH-Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product.
- Knaus, Tanja,B?hmer, Wesley,Mutti, Francesco G.
-
p. 453 - 463
(2017/08/14)
-
- SYNTHESIS OF AMIDES AND AMINES FROM ALDEHYDES OR KETONES BY HETEROGENEOUS METAL CATALYSIS
-
This invention concerns the first mild and efficient synthesis of primary amines and amides from aldehydes or ketones using a heterogeneous metal catalystand amine donor. The initial heterogeneous metal- catalyzed reaction between the carbonyl and the amine donor components is followed up with the addition of a suitable acylating agent component in one-pot. Hence, the present invention provides a novel catalytic one-pot three-component synthesis of amides. Moreover, the integration of enzyme catalysis allows for eco-friendly one-pot co-catalytic synthesis ofamides from aldehyde and ketone substrates, respectively. The process can be applied to the co-catalytic one-pot three-component synthesis of capsaicin and its analogues from vanillin or vanillyl alcohol. It can also be applied for asymmetric synthesis. In the present invention, a novel co-catalytic reductive amination/dynamic kinetic resolution (dkr) relay sequence for the asymmetric synthesis of optically active amides from ketones is disclosed. Moreover, implementation of a catalytic reductive amination/kinetic resolution (kr) relay sequence produces the corresponding optically active amide product and optical active primary amine product with the opposite stereochemistry from the starting ketones.
- -
-
Page/Page column 25
(2016/07/05)
-
- Integrated Heterogeneous Metal/Enzymatic Multiple Relay Catalysis for Eco-Friendly and Asymmetric Synthesis
-
Organic synthesis is in general performed using stepwise transformations where isolation and purification of key intermediates is often required prior to further reactions. Herein we disclose the concept of integrated heterogeneous metal/enzymatic multiple relay catalysis for eco-friendly and asymmetric synthesis of valuable molecules (e.g., amines and amides) in one-pot using a combination of heterogeneous metal and enzyme catalysts. Here reagents, catalysts, and different conditions can be introduced throughout the one-pot procedure involving multistep catalytic tandem operations. Several novel cocatalytic relay sequences (reductive amination/amidation, aerobic oxidation/reductive amination/amidation, reductive amination/kinetic resolution and reductive amination/dynamic kinetic resolution) were developed. They were next applied to the direct synthesis of various biologically and optically active amines or amides in one-pot from simple aldehydes, ketones, or alcohols, respectively.
- Palo-Nieto, Carlos,Afewerki, Samson,Anderson, Mattias,Tai, Cheuk-Wai,Berglund, Per,Córdova, Armando
-
p. 3932 - 3940
(2016/07/06)
-
- METHOD FOR PRODUCING NOVEL ORGANOMETALLIC COMPLEX AND AMINE COMPOUND
-
The purpose of the invention is to provide a novel organometallic compound that can be utilized as a catalyst having high generality, high activity, and excellent functional group selectivity. The invention pertains to a novel organometallic compound represented by general formula (1) that catalyzes a reductive amination reaction.
- -
-
Paragraph 0206
(2016/03/19)
-
- Identification of novel thermostable ω-transaminase and its application for enzymatic synthesis of chiral amines at high temperature
-
A novel thermostable ω-transaminase from Thermomicrobium roseum which showed broad substrate specificity and high enantioselectivity was identified, expressed and biochemically characterized. The advantage of this enzyme to remove volatile inhibitory by-products was demonstrated by performing asymmetric synthesis and kinetic resolution at high temperature.
- Mathew, Sam,Deepankumar, Kanagavel,Shin, Giyoung,Hong, Eun Young,Kim, Byung-Gee,Chung, Taeowan,Yun, Hyungdon
-
p. 69257 - 69260
(2016/08/05)
-
