scholarly journals Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2140 ◽  
Author(s):  
Wesley Böhmer ◽  
Lucien Koenekoop ◽  
Timothée Simon ◽  
Francesco G. Mutti
Keyword(s):  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Molar Ratio ◽  
Chiral Amines ◽  
Aqueous Environment ◽  
Chiral Amine ◽  
Parallel Kinetic Resolution ◽  
Pharmaceutical Manufacture ◽  
Prochiral Ketones ◽  
Asymmetric Transformation

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.

Catalytic Asymmetric Transformations of Racemic Aziridines

Synthesis ◽  
2020 ◽  
Vol 52 (12) ◽  
pp. 1738-1750 ◽  
Author(s):  
Zhuo Chai
Keyword(s):  
Ring Opening ◽  
Kinetic Resolution ◽  
Short Review ◽  
Asymmetric Transformations ◽  
Parallel Kinetic Resolution ◽  
Donor Acceptor ◽  
Molecular Architectures ◽  
Catalytic Asymmetric ◽  
Asymmetric Transformation ◽  
Asymmetric Ring Opening

The catalytic asymmetric ring-opening transformations of aziridines represent an important strategy for the construction of various chiral nitrogen-containing molecular architectures. This short review covers the progress achieved in the catalytic asymmetric transformation of racemic aziridines, focusing on the catalytic strategies employed for each different type of such aziridines.1 Introduction2 Reaction of Racemic 2-Vinylaziridines3 Reaction of Racemic 2-Alkylaziridines3.1 Regiodivergent Parallel Kinetic Resolution3.2 Kinetic Resolution4 Reaction of Racemic 2-(Hetero)arylaziridines4.1 Kinetic Resolution4.2 Enantioconvergent Transformation5 Reaction of Racemic Donor–Acceptor-Type Aziridines6 Conclusion and Outlook

Optimization of Chiral Resolution of (+/-)-1-Phenylethanol by Statistical Methods

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Ganapati D. Yadav ◽  
Jyoti B. Sontakke
Keyword(s):  
Kinetic Resolution ◽  
Batch Reactor ◽  
Immobilized Lipase ◽  
Enantiomeric Excess ◽  
Molar Ratio ◽  
Catalyst Loading ◽  
Acyl Donor ◽  
Reaction Conditions ◽  
Optimum Reaction ◽  
Synthetic Intermediate

Optically active 1-phenylethanol is used as a chiral building block and synthetic intermediate in pharmaceutical and fine-chemical industries. Lipase - catalyzed kinetic resolution of (R,S)-1-phenylethanol with vinyl acetate as an acyl donor and Candida antarctica immobilized lipase as a biocatalyst in a batch reactor was optimized using Response Surface Methodology (RSM). Four-factor-five-level central composite rotatable design (CCRD) was employed to evaluate the effect of synthesis parameters such as speed of agitation, enzyme loading, temperature and acyl donor/alcohol molar ratio, on conversion, enantiomeric excess (ee), enantioselectivity and initial rate. Optimum reaction conditions obtained were; mole ratio of acyl donor: ester of 2:1, temperature of 42.5 °C, catalyst loading of 1.6x10-3 g.cm-3 and speed of agitation of 336 rpm. Analysis of variance was performed to determine significantly affecting variables and interactions between the process parameters.

Probing the Parallel Kinetic Resolution of Racemic Oxazolidinones using Quasi-enantiomeric Profens

2006 ◽  
Author(s):  
Jason Eames ◽  
Gregory Coumbarides ◽  
Marco Dingjan ◽  
Tony Flinn ◽  
Northern Northen ◽  
...  
Keyword(s):  
Kinetic Resolution ◽  
Parallel Kinetic Resolution

scholarly journals Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol

Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 503
Author(s):  
Morten Gundersen ◽  
Guro Austli ◽  
Sigrid Løvland ◽  
Mari Hansen ◽  
Mari Rødseth ◽  
...  
Keyword(s):  
Building Block ◽  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Catalytic Amount ◽  
Building Blocks ◽  
Β Blocker ◽  
Β Blockers ◽  
Optical Rotations ◽  
Reported Data ◽  
By Products

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.

scholarly journals ω-Amino Acid:Pyruvate Transaminase from Alcaligenes denitrificans Y2k-2: a New Catalyst for Kinetic Resolution of β-Amino Acids and Amines

2004 ◽  
Vol 70 (4) ◽  
pp. 2529-2534 ◽  
Author(s):  
Hyungdon Yun ◽  
Seongyop Lim ◽  
Byung-Kwan Cho ◽  
Byung-Gee Kim
Keyword(s):  
Amino Acids ◽  
Kinetic Resolution ◽  
Specific Activity ◽  
Expression System ◽  
Enantiomeric Excess ◽  
Selective Enrichment ◽  
Alcaligenes Denitrificans ◽  
Keto Acids ◽  
Optically Pure ◽  
High Stereoselectivity

ABSTRACT Alcaligenes denitrificans Y2k-2 was obtained by selective enrichment followed by screening from soil samples, which showed ω-amino acid:pyruvate transaminase activity, to kinetically resolve aliphatic β-amino acid, and the corresponding structural gene (aptA) was cloned. The gene was functionally expressed in Escherichia coli BL21 by using an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible pET expression system (9.6 U/mg), and the recombinant AptA was purified to show a specific activity of 77.2 U/mg for l-β-amino-n-butyric acid (l-β-ABA). The enzyme converts various β-amino acids and amines to the corresponding β-keto acids and ketones by using pyruvate as an amine acceptor. The apparent Km and V max for l-β-ABA were 56 mM and 500 U/mg, respectively, in the presence of 10 mM pyruvate. In the presence of 10 mM l-β-ABA, the apparent Km and V max for pyruvate were 11 mM and 370 U/mg, respectively. The enzyme exhibits high stereoselectivity (E > 80) in the kinetic resolution of 50 mM d,l-β-ABA, producing optically pure d-β-ABA (99% enantiomeric excess) with 53% conversion.

scholarly journals Synthesis of enantiomerically pure alcohols and amines via biocatalytic deracemisation methods

2019 ◽  
Vol 9 (20) ◽  
pp. 5487-5503 ◽  
Author(s):  
Musa M. Musa ◽  
Frank Hollmann ◽  
Francesco G. Mutti
Keyword(s):  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Enantiomerically Pure ◽  
Theoretical Maximum

Deracemisation via chemo-enzymatic or multi-enzymatic approaches is the optimum substitute for kinetic resolution, which suffers from the limitation of a theoretical maximum 50% yield albeit high enantiomeric excess is attainable.

Diastereoselective Acylation of Racemic Heterocyclic Amines with N-Phthaloyl and N-Naphthaloyl (S)-Amino Acyl Chlorides: Possibility of Parallel Kinetic Resolution

2018 ◽  
Vol 483 (2) ◽  
pp. 293-296
Author(s):  
D. A. Gruzdev ◽  
E. N. Chulakov ◽  
L. Sh. Sadretdinova ◽  
G. L. Levit ◽  
V. P. Krasnov ◽  
...  
Keyword(s):  
Kinetic Resolution ◽  
Heterocyclic Amines ◽  
Acyl Chlorides ◽  
Parallel Kinetic Resolution
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