1199266-89-1Relevant articles and documents
Multi-enzyme pyruvate removal system to enhance (: R)-selective reductive amination of ketones
Li, Chao,Song, Hao,Zhang, Jinhua,Zhao, Yanshu
, p. 28984 - 28991 (2020)
Biocatalytic transamination is widely used in industrial production of chiral chemicals. Here, we constructed a novel multi-enzyme system to promote the conversion of the amination reaction. Firstly, we constructed the ArR-ωTA/TdcE/FDH/LDH multi-enzyme system, by combination of (R)-selective ω-transaminase derived from Arthrobacter sp. (ArR-ωTA), formate dehydrogenase (FDH) derived from Candida boidinii, formate acetyltransferase (TdcE) and lactate dehydrogenase (LDH) derived from E. coli MG1655. This multi-enzyme system was used to efficiently remove the by-product pyruvate by TdcE and LDH to facilitate the transamination reaction. The TdcE/FDH pathway was found to dominate the by-product pyruvate removal in the transamination reaction. Secondly, we optimized the reaction conditions, including d-alanine, DMSO, and pyridoxal phosphate (PLP) with different concentration of 2-pentanone (as a model substrate). Thirdly, by using the ArR-ωTA/TdcE/FDH/LDH system, the conversions of 2-pentanone, 4-phenyl-2-butanone and cyclohexanone were 84.5%, 98.2% and 79.3%, respectively.
One-Pot Synthesis of Chiral N-Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N-Arylation
Ahmed, Syed T.,Cosgrove, Sebastian C.,Parmeggiani, Fabio,Thompson, Matthew P.,Turner, Nicholas J.
, p. 18156 - 18160 (2020)
The combination of biocatalysis and chemo-catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral-amine-producing biocatalysts with a Buchwald–Hartwig cross-coupling reaction, affording a variety of α-chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual-enzyme biocatalytic hydrogen-borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.
A Process Concept for High-Purity Production of Amines by Transaminase-Catalyzed Asymmetric Synthesis: Combining Enzyme Cascade and Membrane-Assisted ISPR
B?rner, Tim,Rehn, Gustav,Grey, Carl,Adlercreutz, Patrick
, p. 793 - 799 (2015)
For the amine transaminase (ATA)-catalyzed synthesis of chiral amines, the choice of donor substrate is of high importance for reaction and process design. Alanine was investigated as an amine donor for the reductive amination of a poorly water-soluble ketone (4-phenyl-2-butanone) in a combined in situ product removal (ISPR) approach using liquid-membrane extraction together with an enzyme cascade. This ISPR strategy facilitates very high (>98%) product purity with an integrated enrichment step and eliminates product as well as coproduct inhibition. In the presented proof-of-concept alanine shows the following advantages over the other frequently employed amine donor isopropyl amine: (i) nonextractability of alanine affords high product purity without any additional downstream step and no losses via coextraction, (ii) higher maximum reaction rates, and (iii) broader acceptance among ATAs.
Upgraded Bioelectrocatalytic N2 Fixation: From N2 to Chiral Amine Intermediates
Chen, Hui,Cai, Rong,Patel, Janki,Dong, Fangyuan,Chen, Hsiaonung,Minteer, Shelley D.
, p. 4963 - 4971 (2019)
Enantiomerically pure chiral amines are of increasing value in the preparation of bioactive compounds, pharmaceuticals, and agrochemicals. ω-Transaminase (ω-TA) is an ideal catalyst for asymmetric amination because of its excellent enantioselectivity and wide substrate scope. To shift the equilibrium of reactions catalyzed by ω-TA to the side of the amine product, an upgraded N2 fixation system based on bioelectrocatalysis was developed to realize the conversion from N2 to chiral amine intermediates. The produced NH3 was in situ reacted with l-alanine dehydrogenase to generate alanine with NADH as a coenzyme. ω-TA transferred the amino group from alanine to ketone substrates and finally produced the desired chiral amine intermediates. The cathode of the upgraded N2 fixation system supplied enough reducing power to synchronously realize the regeneration of reduced methyl viologen (MV?+) and NADH for the nitrogenase and l-alanine dehydrogenase. The coproduct, pyruvate, was consumed by l-alanine dehydrogenase to regenerate alanine and push the equilibrium to the side of amine. After 10 h of reaction, the concentration of 1-methyl-3-phenylpropylamine achieved 0.54 mM with the 27.6% highest faradaic efficiency and >99% enantiomeric excess (eep). Because of the wide substrate scope and excellent enantioselectivity of ω-TA, the upgraded N2 fixation system has great potential to produce a variety of chiral amine intermediates for pharmaceuticals and other applications.
Immobilization of ω-transaminases by encapsulation in a sol-gel/celite matrix
Koszelewski, Dominik,Mueller, Nicole,Schrittwieser, Joerg H.,Faber, Kurt,Kroutil, Wolfgang
, p. 39 - 44 (2010)
Commercially available ω-transaminases ω-TA-117, -113, and Vibrio fluvialis (Vf-AT) have been immobilized in a sol-gel matrix. Improved results were obtained by employing Celite 545 as additive. The immobilized ω-transaminases ω-TA-117, -113, and V. fluvialis (Vf-AT) were tested in the kinetic resolution of α-chiral primary amines. In contrast to the free enzyme ω-TA-117, the sol-gel/celite immobilized enzyme showed activity even at pH 11. Recycling of the sol-gel/Celite 545 immobilized ω-transaminase ω-TA-117 was performed over five reaction cycles without any substantial loss in enantioselectivity and conversion. Finally, the immobilized ω-TA 117 was employed in a one-pot two-step deracemization of rac-mexiletine and rac-4-phenyl-2-butylamine, two pharmacologically relevant amines. The corresponding optically pure (S)-amines were obtained in up to 95% isolated yield (>99% ee).
Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β- and γ-Amino Acids Using Transaminase
Kim, Geon-Hee,Jeon, Hyunwoo,Khobragade, Taresh P.,Patil, Mahesh D.,Sung, Sihyong,Yoon, Sanghan,Won, Yumi,Sarak, Sharad,Yun, Hyungdon
, p. 1437 - 1440 (2019)
A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α-ketoglutarate. Various enantiopure β-, γ-amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.
Thiyl radical mediated racemization of nonactivated aliphatic amines
Escoubet, Stephanie,Gastaldi, Stephane,Vanthuyne, Nicolas,Gil, Gerard,Siri, Didier,Bertrand, Michele P.
, p. 7288 - 7292 (2006)
The racemization of nonactivated aliphatic amines has been mediated with alkanethiols and with methyl thioglycolate in the presence of AIBN. The process involves reversible H-abstraction at the chiral center, in a position α relative to nitrogen, by thiyl radical. The knowledge of the reaction enthalpy is critical to select the appropriate thiol. In the absence of experimental values, theoretical calculations of the α-C-H BDEs and the S-H BDE provide a useful guide.
New Simple Polymeric Supports with Hydrazone Linkers for Solid-Phase Synthesis of Ketones and Primary Amines
Lazny, Ryszard,Nodzewska, Aneta,Wolosewicz, Karol
, p. 2858 - 2864 (2003)
The preparation of new solid supports with hydrazine anchoring groups and their application to solid-phase synthesis of ketones and primary amines are described. The supports were used for immobilization of ketones, 4-tert-butylcyclohexanone, pentan-3-one, acetone, N-methylpiperidone, N-benzylpiperidone, and tropinone in the form of their hydrazones. The polymer-supported hydrazones were subjected to deprotonation/alkylation procedure (LDA/RX) once or twice. The resulting alkylated products were cleaved off the solid support on treatment with trifluoroacetic acid in tetrahydrofuran providing α-alkylated or α,α′-bisalkylated ketones or were subjected to reductive cleavage with borane in tetrahydrofuran to give β-alkylated or β,β′-bisalkylated primary amines.
Coupled Immobilized Amine Dehydrogenase and Glucose Dehydrogenase for Asymmetric Synthesis of Amines by Reductive Amination with Cofactor Recycling
Liu, Ji,Pang, Bryan Q. W.,Adams, Joseph P.,Snajdrova, Radka,Li, Zhi
, p. 425 - 431 (2017)
The amine dehydrogenase (AmDH) engineered from the phenylalanine dehydrogenase of Rhodococcus sp. M4 was directly immobilized on magnetic nanoparticles (MNP) from the cell-free extract containing his-tagged AmDH through affinity attachment to give AmDH-MNPs with high yield, enzyme loading efficiency, and specific enzyme loading. AmDH-MNPs showed higher activity and productivity than the free enzyme for the asymmetric reductive amination of 4-phenyl-2-butanone 1 a and phenylacetone 1 b, producing the corresponding amines (R)-2 a,b in 99 % ee and 99 % yield, and with recycling of NADH for up to 3956 times. AmDH-MNPs were easily recycled, retaining 91 % of the original productivity in the third cycle of the reductive amination of 1 a. Coupling of immobilized AmDH and immobilized glucose dehydrogenase (GDH) for the asymmetric reductive amination of 1 a gave (R)-2 a in 99 % ee and 74 % yield, with a total turnover number (TTN) of 2940 for NADH recycling. Both immobilized enzymes showed good recyclability, retaining 81 % productivity in the third reaction cycle. The developed method with coupled immobilized AmDH and immobilized GDH for the asymmetric reductive amination of ketones is useful for the synthesis of enantiopure amines, superior to the use of coupled isolated enzymes with enhanced catalytic performance and reduced enzyme cost through catalyst recycling.
Vicinal Diamines as Smart Cosubstrates in the Transaminase-Catalyzed Asymmetric Amination of Ketones
Payer, Stefan E.,Schrittwieser, Joerg H.,Kroutil, Wolfgang
, p. 2553 - 2559 (2017)
Transaminases (TAs) have recently been established as catalysts for the asymmetric, reductive amination of prochiral ketones. Depending on the ketone substrate and the amine donor (the cosubstrate), equilibrium constants may limit high conversions; thus, methods to overcome this limitation are required. Removal of the co-product from the reaction equilibrium through spontaneous, intramolecular reactions has provided a successful solution to this problem; therefore, these amine donors have been named “smart cosubstrates”. Here, we present a comparison of various bifunctional amine donors including vicinal diamines as potential structural cosubstrate motifs. Upon TA-catalyzed deamination of 1,2-diamines, spontaneous dimerization of the resulting α-aminoketones and oxidation gave heteroaromatic pyrazines.
Development of a: Corynebacterium glutamicum bio-factory for self-sufficient transaminase reactions
Grigoriou, Stylianos,Kugler, Pierre,Kulcinskaja, Evelina,Walter, Frederik,King, John,Hill, Phil,Wendisch, Volker F.,O'Reilly, Elaine,O'Reilly, Elaine
, p. 4128 - 4132 (2020)
The development of biocatalytic routes for the synthesis of chiral amines starting from achiral building blocks is highly desirable. Here, we report a self-sufficient whole-cell system for the conversion of a model ketone to the corresponding cyclic imine, in good isolated yield (42%) and excellent enantioselectivity (>99% ee). The Corynebacterium glutamicum host produces the transaminase biocatalyst, cofactor and 'smart' amine donor (cadaverine or putrescine) in vivo, and highlights the potential for producing high-value chemicals from readily available building blocks. The report represents the first example of the application of a metabolically engineered organism for the production of smart diamine donors and their application in a transaminase biotransformation.
Two-Step Protocol for Iodotrimethylsilane-Mediated Deoxy-Functionalization of Alcohols
Chen, Yuming,He, Ru,Song, Hongjian,Yu, Guoqing,Li, Chenglin,Liu, Yuxiu,Wang, Qingmin
, p. 1179 - 1183 (2021/02/01)
We have developed a two-step protocol for iodotrimethylsilane-mediated deoxy-functionalization of primary and secondary alcohols to afford products containing a C?N, C?S, or C?O bond. In the first step the alcohol undergoes iodination with iodotrimethylsilane, and in the second, the iodine atom is replaced by a N, S, or O nucleophile. Compared with traditional Mitsunobu reaction, non-acidic pre-nucleophiles can be used, and the reaction proceeds with retention of configuration. This operationally simple, highly efficient protocol can be used for some natural products and small-molecule drugs containing hydroxy-group.
Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(iii) complexes bearing an amidato ligand
Dai, Zengjin,Pan, Ying-Min,Wang, Shou-Guo,Yin, Qin,Zhang, Xumu
supporting information, p. 8934 - 8939 (2021/11/04)
A series of half-sandwich Ir(iii) complexes1-6bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%). Asymmetric transformation was also attempted with chiral Ir complexes3-6, and 16% ee of the desired primary amine was obtained. Despite the unsatisfactory enantio-control achieved so far, the current exploration might stimulate more efforts towards the discovery of better chiral catalysts for this challenging but important transformation.
