115880-49-4Relevant academic research and scientific papers
Chiral Phosphinyl Enamines and Their Asymmetric Reduction through Group-Assisted Purification Chemistry Leading to Enantiopure β-Amino Esters/Amides
Qiao, Shuo,Wu, Jianbin,Mo, Junming,Spigener, Preston T.,Zhao, Brian Nlong,Jiang, Bo,Li, Guigen
, p. 2483 - 2488 (2017)
A series of new chiral N -phosphinyl β-enamino esters and amides were successfully prepared with excellent Z -stereoselectivity (Z / E > 99:1 in nearly all cases). Group-assisted purification chemistry proved to be an efficient method for the asymmetric reduction of the resulting β-enamino esters/amides to give enantiopure β-amino esters/amides. The asymmetric reduction can be controlled efficiently by using a combination of sodium cyanoborohydride and acetic acid.
Sequential resolution of ethyl 3-aminobutyrate with carboxylic acid esters by Candida antarctica lipase B
Gedey, Szilvia,Liljeblad, Arto,Fueloep, Ferenc,Kanerva, Liisa T.
, p. 2573 - 2581 (1999)
The reactions of ethyl 3-aminobutyrate 1 with carboxylic acid esters, catalyzed by lipases from Candida antarctica, Pseudomonas cepacia and Pseudomonas fluorescens, have been studied. The reactions take place on the amino and ester functions of the substrate provided that the alkyl group of the achiral ester differs from ethyl. This property has been exploited for the Candida antarctica lipase B-catalyzed resolution of 1 in butyl butyrate, leading to the unreacted enantiomer (S)-1 and butyl 3-aminobutyrate, and to the butanamide of butyl (R)-3-aminobutyrate.
Candida antarctica lipase catalyzed resolution of ethyl (±)-3-aminobutyrate
Sanchez, Victor M.,Rebolledo, Francisca,Gotor, Vicente
, p. 37 - 40 (1997)
Candida antarctica lipase efficiently catalyzes acetylation and hydrolysis of ethyl (±)-3-aminobutyrate.
Amination of ketones by employing two new (S)-selective ω-transaminases and the his-tagged ω-TA from Vibrio fluvialis
Mutti, Francesco G.,Fuchs, Christine S.,Pressnitz, Desiree,Turrini, Nikolaus G.,Sattler, Johann H.,Lerchner, Alexandra,Skerra, Arne,Kroutil, Wolfgang
, p. 1003 - 1007 (2012)
Two recently identified (S)-selective ω-transaminases (ω-TAs) that originate from Paracoccus denitrificans (Strep-PD-ωTA, cloned with an N-terminal Strep-tag II) and Pseudomonas fluorescens (PF-ωTA) were employed for the asymmetric amination of selected prochiral ketones. The substrates tested were transformed into optically pure amines (>99 % ee) with high conversion (up to >99 %). The ω-TAs led to higher conversion in the absence of dimethyl sulfoxide as a cosolvent than in its presence (15 %, v/v). Additionally, it was shown that a His-tagged recombinant transaminase from Vibrio fluvialis (His-VF-ωTA, cloned with an N-terminal His 6-tag) showed for a single substrate, ethyl acetoacetate, significantly higher stereoselectivity for the amination compared to the corresponding commercial enzyme preparation (>99 vs. 50 %). The (S)-selective ω-transaminases (ω-TAs) from Paracoccus denitrificans and Pseudomonas fluorescens transformed various ketones into optically pure amines (>99 % ee). These enzymes extend the substrate spectrum of highly (S)-stereoselective ω-TAs. Copyright
Asymmetric bio-amination of ketones in organic solvents
Mutti, Francesco G.,Kroutil, Wolfgang
, p. 3409 - 3413 (2012)
ω-Transaminases, employed as a lyophilised crude cell-free extract, were successfully employed in organic solvent for the asymmetric amination of ketones without the need for immobilisation. Best activity was found for methyl tert-butyl ether (MTBE) at a water activity of 0.6. The ω-transaminases (9 different enzymes) accepted efficiently 2-propylamine as amine donor when used in the solvent, which is not the case when they are used in aqueous solution. The bio-amination in organic solvent showed several advantages such as higher reaction rates (up to 17-fold), general acceptance of 2-propylamine as amine donor, simple work-up procedure (i.e., no basification and extraction required), easy recycling of the catalyst and lack of substrate inhibition. The biocatalysts maintained their excellent stereoselectivity in MTBE allowing the preparation of optically pure amines (ee >99%) with up to >99% conversion.
Stereoselectivity of four (R)-selective transaminases for the asymmetric amination of ketones
Mutti, Francesco G.,Fuchs, Christine S.,Pressnitz, Desiree,Sattler, Johann H.,Kroutil, Wolfgang
, p. 3227 - 3233 (2011)
Four (R)-ω-transaminases originating from Hyphomonas neptunium (HN-ωTA), Aspergillus terreus (AT-ωTA) and Arthrobacter sp. (ArR-ωTA), as well as an evolved transaminase (ArRmut11-ωTA) were successfully employed for the amination of prochiral ketones leading to optically pure (R)-amines. The first three transaminases displayed perfect stereoselectivity for the amination of all substrates tested (ee >99%). Furthermore, the transaminase AT-ωTA led in most cases to better conversion than ArR-ωTA and HN-ωTA using D-alanine as amine donor. α-Tetralone, which was the only substrate not accepted by HN-ωTA, ArR-ωTA, and AT-ωTA, was successfully transformed with perfect enantioselectivity (ee >99%) into the corresponding optically pure amine employing the variant ArRmut11-ωTA. Copyright
Structural effects on chemo- and enantioselectivity of Candida antarctica lipase B - Resolution of β-amino esters
Gedey, Szilvia,Liljeblad, Arto,Lazar, Laszlo,Fueloep, Ferenc,Kanerva, Liisa T.
, p. 565 - 570 (2002)
The Candida antarctica lipase B-catalyzed reactions of five β-amino esters with neat butyl butanoate and with 2,2,2-trifluoroethyl butanoate in diisopropyl ether were studied, as were the reactions of the same β-amino esters and their N-butanamides with neat butanol. The possibility for sequential resolution, where the amino and ester functions of the substrate both react with an achiral butanoate, became less likely with increasing size of the substrate from ethyl 3-aminobutanoate (1a) to pentanoate (1b) or larger. On the other hand, the alcoholyses of N-acylated β-amino esters successfully proceeded in butanol with E > 100. Gram-scale resolution of the N-butanoylated 1a was performed to demonstrate the usefulness of the method.
Enantioselective acylation of β-aminoesters using penicillin G acylase in organic solvents
Roche, Didier,Prasad, Kapa,Repic, Oljan
, p. 3665 - 3668 (1999)
The resolution of racemic β-aminoesters has been achieved through selective acylation catalyzed by Penicillin G Acylase (ChiroCLEC(TM)-EC). The method has been optimized using three different phenylacetyl donors, and the effect of solvents on the rate of reaction is described. The efficiency of our method is illustrated by the synthesis of five different β-aminoesters with high enantiomeric purities.
Parallel interconnected kinetic asymmetric transformation (PIKAT) with an immobilized ω-transaminase in neat organic solvent
B?hmer, Wesley,Koenekoop, Lucien,Mutti, Francesco G.,Simon, Timothée
, (2020/05/25)
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.
QUINOLINONE PYRIMIDINES COMPOSITIONS AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS
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Paragraph 0619; 0624; 0625, (2016/04/19)
The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, B, W1, W2, W3, and R1-R6 are described herein.
