Zwei Schritte in einem Reaktionsgefäß: Enzymkaskaden zur selektiven Synthese von Nor(pseudo)ephedrin aus kostengünstigen Ausgangsmaterialien

Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Wardenga, Rainer; Lieres, Eric von; Offermann, Heike; Westphal, Robert; Pohl, Martina; Rother, Dörte

doi:10.1002/ange.201300718

Cited by 37 publications

(3 citation statements)

References 27 publications

(17 reference statements)

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“…Due to the constant innovation in protein engineering, the application of biocatalysts represents a valuable addition to conventional chemistry 11. In particular, biocatalytic routes to compounds with more than one chiral centre have a great potential, as in theory all diastereomers can be accessed in a step‐efficient manner12 with high optical purity owing to the often excellent stereo‐ and regioselectivity of enzymes 13. If the reaction parameters are suitable, both enzyme reactions can be conducted in one pot or even in a cascade reaction.…”

Section: Introductionmentioning

confidence: 99%

“…For example, the use of an engineered ATA in the synthesis of a 1,2‐amino alcohol was recently shown 14. Combining the ( R )‐selective thiamine diphosphate‐dependent (ThDP) acetohydroxyacid synthase I (AHAS‐I) and either an ( S )‐ or ( R )‐selective amine transaminase (ATA) in a stepwise fashion allowed the synthesis of either norephedrine (NE) or norpseudoephedrine (NPE), respectively 12. The isomer (1 S ,2 S )‐NPE, also known as cathine, was accessible by combination of an ( S )‐selective ATA with an ( S )‐selective alcohol dehydrogenase in high optical purity 15.…”

Section: Introductionmentioning

confidence: 99%

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Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction

et al. 2015

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Theb iocatalytic synthesis of chiral amines has become av aluable addition to the chemists toolbox. However, the efficient asymmetric synthesis of functionalised amines bearing more than one stereocentre,s uch as 1,3-aminoa lcohols, remains challenging. By employing ak eto reductase (KRED) and two enantiocomplementary amine transaminases (ATA), we developed ab iocatalytic route towards all four diastereomers of 4-amino-1-phenylpentane-2-ol as ar epresentative molecule bearing the 1,3amino alcohol functionality.S tarting from ar acemic hydroxy ketone,akinetic resolution using an (S)-selective KRED provided optically active hydroxy ketone( 86% ee)a nd the corresponding diketone.Furthert ransamination of the hydroxy ketone was performed by either an (R)-or an (S)-selective ATA, yieldingt he (2R,4R)-and (2R,4S)-1,3-amino alcohol diastereomers. Ther emaining two diastereomers were accessible in twos ubsequent asymmetric steps: the diketonew as reducedr egio-ande nantioselectively by the same KRED, which yielded the (S)-configuredh ydroxy ketone.E ventually, the subsequent transamination of the crude product with (R)-and (S)-selective ATAs yielded the remaining (2S,4R)and (2S,4S)-diastereomers,respectively.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction

et al. 2015

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“…Similar molecules such as norpseudoepinephrine ((1 R ,2 R )‐NPE) and norepinephrine ((1 R ,2 S )‐NE) have been successfully produced at 10 mM scale via a one‐pot two‐step batch cascade starting from pyruvate. Employing a thiamine diphosphate (ThDP)‐dependent acetohydroxy acid synthase I (AHAS−I) followed by ( S )‐ or ( R )‐selective ω‐transaminases (TAs), (1 R ,2 R )‐NPE and (1 R ,2 S )‐NE have been obtained with 85 % and 80 % m.c., respectively [8] …”

Section: Introductionmentioning

confidence: 99%

Mimicking Natural Metabolisms: Cell‐Free Flow Preparation of Dopamine

et al. 2022

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The biosynthesis of dopamine (DA) from L-tyrosine as starting material is an excellent yet challenging strategy. Here we developed a versatile, multi-enzymatic platform for the biocatalytic preparation of DA in a continuous mode with excellent conversion (90 %) and reaction time (45 min). The system exploits the immobilization of a decarboxylase from Bacillus pumilis (Fdc) and a tyrosinase from Agaricus bisporus (Tyr), which were combined to mimic the in-vivo synthesis of DA (both primary and secondary metabolisms) giving rise to an efficient strategy with a considerable reduction of process associated costs and environmental impact. To enhance the system automation, an in-line purification via catch-and-release procedure was added.

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Dynamic Kinetic Resolution of 2‐Phenylpropanal Derivatives to Yield β‐Chiral Primary Amines via Bioamination

et al. 2014

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The amination of racemic a-chiral aldehydes, 2-phenylpropanal derivatives, was investigated employing w-transaminases. By medium and substrate engineering the optical purity of the resulting b-chiral chiral amine could be enhanced to reach optical purities up to 99% ee. Using enantiocomplementary w-transaminases allowed us to access the (R)-as well as the (S)-enantiomer in most cases. It is important to note that the stereopreference of the w-transaminases found for a-chiral aldehydes did not correlate with the stereopreference previously observed for the amination of methyl ketones. In one case the stereopreference switched even upon exchanging a methyl substituent to a methoxy group.

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Zwei Schritte in einem Reaktionsgefäß: Enzymkaskaden zur selektiven Synthese von Nor(pseudo)ephedrin aus kostengünstigen Ausgangsmaterialien

Cited by 37 publications

References 27 publications

Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction

Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction

Mimicking Natural Metabolisms: Cell‐Free Flow Preparation of Dopamine

Dynamic Kinetic Resolution of 2‐Phenylpropanal Derivatives to Yield β‐Chiral Primary Amines via Bioamination

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