3886-69-9Relevant articles and documents
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
Albert, Joan,D'Andrea, Luci?a,Granell, Jaume,Tavera, Raquel,Font-Bardia, Mercè,Solans, Xavier
, p. 3070 - 3080 (2007)
(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.
Crystallization-based resolution of 1,4-benzodioxane-2-carboxylic acid enantiomers via diastereomeric 1-phenylethylamides
Fumagalli, Laura,Bolchi, Cristiano,Bavo, Francesco,Pallavicini, Marco
, p. 2009 - 2011 (2016)
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.
Determination of absolute configurations of amines and amino acids using nonchiral derivatizing agents (NCDA) and deuterium NMR.
Chalard,Bertrand,Canet,Thery,Remuson,Jeminet
, p. 2431 - 2434 (2000)
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.
Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
supporting information, p. 390 - 398 (2021/01/13)
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.
Rational Design of Chiral Nanohelices from Self-Assembly of Meso-tetrakis (4-Carboxyphenyl) Porphyrin-Amino Acid Conjugates
Yang, Xuejiao,Shen, Yuhe,Liu, Jiayu,Wang, Yuefei,Qi, Wei,Su, Rongxin,He, Zhimin
, p. 13067 - 13074 (2021/11/16)
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.
Transaminase Engineering and Process Development for a Whole-Cell Neat Organic Process to Produce (R)-α-Phenylethylamine
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
, (2022/01/04)
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.
Artificial plant cell walls as multi-catalyst systems for enzymatic cooperative asymmetric catalysis in non-aqueous media
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)
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.
Method for recycling perindopril intermediate resolving agent (R)-(+)-alpha-phenylethylamine
-
Paragraph 0045-0048, (2021/07/10)
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.
Generation of Oxidoreductases with Dual Alcohol Dehydrogenase and Amine Dehydrogenase Activity
Tseliou, Vasilis,Schilder, Don,Masman, Marcelo F.,Knaus, Tanja,Mutti, Francesco G.
supporting information, p. 3315 - 3325 (2020/12/11)
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.
Biochemical and Structural Characterization of an (R)-Selective Transaminase in the Asymmetric Synthesis of Chiral Hydroxy Amines
Li, Fulong,Liang, Youxiang,Wei, Yuwen,Zheng, Yukun,Du, Yan,Yu, Huimin
supporting information, p. 4582 - 4589 (2021/08/07)
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.).
