2627-86-3Relevant articles and documents
Catalytic Behaviour of Optically Active Amino Alcohol-Borane Complex in the Enantioselective Reduction of Acetophenone Oxime O-Alkyl Ethers
Itsuno, Shinichi,Sakurai, Yoshiki,Ito, Koichi,Hirao, Akira,Nakahama, Seiichi
, p. 395 - 396 (1987)
In the presence of the optically active amino alcohol-borane complex, an oxime ether was reduced with various hydride reducing agents to give a chiral primary amine of high optical purity.Catalytic use of the chiral complex was also investigated.
Influence of Z,E-isomerism on the chiral-optical properties of amides
Dem'yanovich,Shishkina
, p. 807 - 811 (1996)
The study of the chiral-optical properties of N-acyl-(-)-1-methyl-1,2,3,4-tetrahydroisoquinolines and their acyclic analogs, the n-acyl-(-)-1-phenylethylamines, with the known ratio of Z- and E-isomers showed that the Z-isomers are characterized by the negative Cotton effect in the region of the absorption band of the amide chromophore. The observed Cotton effects of amides of phenylethy lamine, which are higher by comparison with those of amides of tetrahydroisoquinoline, are explained by the interaction of the amide and aromatic chromophores, which are in proximity in certain conformations, possible for acyclic conformationally free phenylethylamides. 1997 Plenum Publishing Corporation.
Tuneable 3D printed bioreactors for transaminations under continuous-flow
Peris, Edgar,Okafor, Obinna,Kulcinskaja, Evelina,Goodridge, Ruth,Luis, Santiago V.,Garcia-Verdugo, Eduardo,O'Reilly, Elaine,Sans, Victor
, p. 5345 - 5349 (2017)
A method to efficiently immobilize enzymes on 3D printed continuous-flow devices is presented. Application of these chemically modified devices enables rapid screening of immobilization mechanisms and reaction conditions, simple transfer of optimised conditions into tailored printed microfluidic reactors and development of continuous-flow biocatalytic processes. The bioreactors showed good activity (8-20.5 μmol h-1 mgenz-1) in the kinetic resolution of 1-methylbenzylamine, and very good stability (ca. 100 h under flow).
Chromobacterium violaceum ω-transaminase variant Trp60Cys shows increased specificity for (S)-1-phenylethylamine and 4′-substituted acetophenones, and follows Swain-Lupton parameterisation
Cassimjee, Karim Engelmark,Humble, Maria Svedendahl,Land, Henrik,Abedi, Vahak,Berglund, Per
, p. 5466 - 5470 (2012)
For biocatalytic production of pharmaceutically important chiral amines the ω-transaminase enzymes have proven useful. Engineering of these enzymes has to some extent been accomplished by rational design, but mostly by directed evolution. By use of a homology model a key point mutation in Chromobacterium violaceum ω-transaminase was found upon comparison with engineered variants from homologous enzymes. The variant Trp60Cys gave increased specificity for (S)-1-phenylethylamine (29-fold) and 4′-substituted acetophenones (～5-fold). To further study the effect of the mutation the reaction rates were Swain-Lupton parameterised. On comparison with the wild type, reactions of the variant showed increased resonance dependence; this observation together with changed pH optimum and cofactor dependence suggests an altered reaction mechanism.
Towards a continuous dynamic kinetic resolution of 1-phenylethylamine using a membrane assisted, two vessel process
Roengpithya, Chayaporn,Patterson, Darrell A.,Livingston, Andrew G.,Taylor, Paul C.,Irwin, Jacob L.,Parrett, Mark R.
, p. 3462 - 3463 (2007)
A continuous process with two separated reaction vessels provides a solution to the problems surrounding the combination of two catalysts in dynamic kinetic resolution reactions by retaining the biocatalyst in a lower temperature vessel with a microfiltration membrane and allowing the racemisation to occur efficiently in a higher temperature vessel. The Royal Society of Chemistry.
'Easy-on, easy-off' resolution of chiral 1-phenylethylamine catalyzed by Candida antarctica lipase B
Torres-Gavilan,Escalante,Regla,Lopez-Munguia,Castillo
, p. 2621 - 2624 (2007)
An 'easy-on, easy-off' process for the effective resolution of (±)-1-phenylethylamine was designed using the lipase B of Candida antarctica. This two step lipase-catalyzed process for the resolution of a chiral arylalkylamine involves a high-conversion enantioselective condensation of (R)-(+)-1-phenylethylamine with capric acid (conversion 99%, 24 h), followed by the hydrolysis of the corresponding synthesized (R)-(+)-amide (conversion 98%, 48 h). As a result, this efficient enzymatic process yields both (R)- and (S)-enantiomers of 1-phenylethylamine in high enantiomeric purity.
Rapid screening and scale-up of transaminase catalysed reactions
Truppo, Matthew D.,Rozzell, J. David,Moore, Jeffrey C.,Turner, Nicholas J.
, p. 395 - 398 (2009)
A rapid, high-throughput screening methodology has been developed for the determination of transaminase activity. This pH based, colorimetric assay can also be used to scale reactions directly from 100 μL screening scale to 25 mL development scale. Additionally, three techniques have been developed to drive transamination reactions toward complete conversion. The first method uses lactate dehydrogenase to remove the inhibitory pyruvate keto acid by-product from the reaction and drive reaction equilibrium toward the desired amine. The second method is a single enzyme system, and uses a large excess of isopropylamine to drive the transamination. Method three requires only a catalytic amount of amine donor, as an amino acid dehydrogenase is employed to regenerate the amine donor in situ using ammonia. All three systems have been demonstrated for the production of optically pure methylbenzylamine from acetophenone. An enantiomeric excess of >99% was achieved for both the R- and S-methylbenzylamine products.
Reciprocal resolutions between 1-phenylethylamine and carboxyesters of isopropylidene glycerol: Improvement of the method by replacing mono-phthalate with 3-carboxy-2-naphthoate
Pallavicini, Marco,Valoti, Ermanno,Villa, Luigi,Piccolo, Oreste
, p. 2489 - 2495 (2001)
A novel resolving agent, isopropylidene glycerol 3-carboxy-2-naphthoate 2, was designed on the basis of the consideration that replacement of phenyl group with a naphthyl group would improve the resolving ability of isopropylidene glycerol hydrogen phthalate 1 while also conferring more suitable physicochemical properties for such a specific use. Indeed, 1-phenylethylamine 4 was resolved by 2 more efficiently than by 1 (respective resolution efficiencies, (S) 0.88 and 0.81), while 1 and 2 were resolved by 4 with S ranging between 0.54 and 0.59. Furthermore, 2 is a solid, whereas 1 is a viscous oil, and its recovery at the end of the resolution procedure is easier than that of 1. In order to understand the chiral discrimination mechanism of the two reciprocal resolutions, the binary melting point phase diagrams of the four diastereomeric systems (S)-2·(S)-4/(S)-2·(R)-4, (S)-2·(S)-4/(R)-2·(S)-4, (S)-1·(S)-4/(S)-1·(R)-4 and (S)-1·(S)-4/(R)-1·(S)-4 were determined. The first two systems form ideal conglomerates, characterised by identical diagrams, in which the eutectic corresponds to a 0.10 molar ratio of (S)-2·(S)-4. The same behaviour was shown by the other two systems, whose eutectics, however, correspond to a 0.18 molar ratio of (S)-1·(S)-4. On the basis of the present results, which indicate an excellent resolution ability of 2 for 4, the application of this new acid to the resolution of other 1-arylalkylamines seems to have very good prospects, worthy of investigation.
Structure Study of Host-Guest Molecular Association in Solution and in the Solid State
Toda, Fumio,Tanaka, Koichi,Ootani, Minoru,Hayashi, Atsuhiro,Miyahara, Ikuko,Hirotsu, Ken
, p. 1413 - 1415 (1993)
A correlation between the mechanism of 1H NMR shift of a chiral guest by association with an optically active host compound in solution and in the solid state is revealed by an X-ray analysis of the host-guest inclusion crystal.
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.
Engineering the large pocket of an (S)-selective transaminase for asymmetric synthesis of (S)-1-amino-1-phenylpropane
Liu, He,Wang, Hualei,Wei, Dongzhi,Xie, Youyu,Xu, Feng,Xu, Xiangyang,Yang, Lin
, p. 2461 - 2470 (2021/04/22)
Amine transaminases offer an environmentally benign chiral amine asymmetric synthesis route. However, their catalytic efficiency towards bulky chiral amine asymmetric synthesis is limited by the natural geometric structure of the small pocket, representing a great challenge for industrial applications. Here, we rationally engineered the large binding pocket of an (S)-selective ?-transaminase BPTA fromParaburkholderia phymatumto relieve the inherent restriction caused by the small pocket and efficiently transform the prochiral aryl alkyl ketone 1-propiophenone with a small substituent larger than the methyl group. Based on combined molecular docking and dynamic simulation analyses, we identified a non-classical substrate conformation, located in the active site with steric hindrance and undesired interactions, to be responsible for the low catalytic efficiency. By relieving the steric barrier with W82A, we improved the specific activity by 14-times compared to WT. A p-p stacking interaction was then introduced by M78F and I284F to strengthen the binding affinity with a large binding pocket to balance the undesired interactions generated by F44. T440Q further enhanced the substrate affinity by providing a more hydrophobic and flexible environment close to the active site entry. Finally, we constructed a quadruple variant M78F/W82A/I284F/T440Q to generate the most productive substrate conformation. The 1-propiophenone catalytic efficiency of the mutant was enhanced by more than 470-times in terms ofkcat/KM, and the conversion increased from 1.3 to 94.4% compared with that of WT, without any stereoselectivity loss (ee > 99.9%). Meanwhile, the obtained mutant also showed significant activity improvements towards various aryl alkyl ketones with a small substituent larger than the methyl group ranging between 104- and 230-fold, demonstrating great potential for the efficient synthesis of enantiopure aryl alkyl amines with steric hindrance in the small binding pocket.
