Asymmetric synthesis of chiral amine in organic solvent and in-situ product recovery for process intensification: A case study

Satyawali, Yamini; Ehimen, Ehiaze Augustine; Cauwenberghs, Lieve; Maesen, Miranda; Vandezande, Pieter; Dejonghe, Winnie

doi:10.1016/j.bej.2016.11.006

Cited by 18 publications

(33 citation statements)

References 21 publications

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“…It is possible that more MPPA could be formed in the reactor phase but was not released into the n-heptane thus escaping extraction. Remarkably, the diffusion of product and therefore product extraction increased when continuously stirring the system at 100 rpm (Figure 4, day [8][9][10][11][12][13][14]. A continuous motion of the inner tubular cylinder, imparted by the stirrer, enhanced product release and thus improved the product extraction.…”

Section: Three-liquid-phase Spinning Reactor For the Transaminasecatamentioning

confidence: 98%

“…The transaminase-mediated synthesis of (S)-1methyl-3-phenylpropylamine (MPPA) was employed as model reaction (Scheme 1). Based on the previous studies, [14,16] n-heptane was selected as organic solvent phase A. The substrate 4-phenyl-2-butanone (BA), initially supplied to phase A, progressively moved to phase C. The enzymatic reaction occurred in phase C, (reaction phase), consisting of the enzyme TA-v2 [25] and the AD (Jeffamine ED-600), not soluble in n-heptane.…”

Section: Three-liquid-phase Spinning Reactor For the Transaminasecatamentioning

confidence: 99%

“…Membraneassisted techniques for in situ product removal have been also investigated. [14][15][16][17] Specifically, membrane-based three liquid phase (3LP) systems were developed by filling the pores of an hydrophobic hollow fibre membrane contactor with an hydrophobic solvent. This operation allowed to physically separate the reaction and the extraction aqueous solutions by using a supported liquid membrane.…”

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confidence: 99%

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Three‐liquid‐phase Spinning Reactor for the Transaminase‐catalyzed Synthesis and Recovery of a Chiral Amine

et al. 2020

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A device for the transaminase‐catalysed synthesis combined with continuous recovery of chiral amines was designed. The system enabled the separation of the reaction components in three liquid phases: a reaction phase, an organic solvent phase (where the poorly water soluble ketone substrate was supplied), and an aqueous extraction phase for continuous product recovery. The transaminase‐mediated asymmetric synthesis of (S)‐1‐methyl‐3‐phenylpropylamine was employed as model reaction. Factors influencing the performance of the system, such as reactor geometry, working volumes and operating parameters, were investigated. Specifically, reaction yield and product recovery were enhanced by i) reducing the thickness of the reaction phase, while continuously stirring and ii) reducing the volume of the extraction phase. Under the optimal condition tested, 85 % of the product formed was extracted and a product concentration value of 9 g/L was reached. However, co‐extraction of the unreacted amine donor (17 %) was observed. Advantages and drawbacks of this process compared to existing technologies, as well as possible optimization strategies are discussed.

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Section: Three-liquid-phase Spinning Reactor For the Transaminasecatamentioning

confidence: 98%

Section: Three-liquid-phase Spinning Reactor For the Transaminasecatamentioning

confidence: 99%

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confidence: 99%

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Three‐liquid‐phase Spinning Reactor for the Transaminase‐catalyzed Synthesis and Recovery of a Chiral Amine

et al. 2020

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“…In contrast, there are only a few reports covering the application of ATAs in pure organic solvents. [2] The first ATA successfully employed in a substantial amount of organic solvent (i. e. 50% DMSO) was reported in 2010 for the synthesis of sitagliptin, [3] where the immobilization of the enzyme permitted even the employment of neat organic solvents. [4] Since then, a number of reports on immobilized transaminases have been published.…”

Section: Introductionmentioning

confidence: 99%

Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates

et al. 2020

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The challenging bioamination of hydrophobic substrates has been attained through the employment of a disperse system consisting of a combination of a low polarity solvent (e. g. isooctane or methyl‐tert‐butylether), a non‐ionic surfactant and a minimal amount of water. In these conditions, amine transaminases (ATA) were shown to efficiently carry out the reductive amination of variously substituted cyclohexanones, providing good conversions often coupled with a superior stereoselectivity if compared with the corresponding chemical reductive amination. An array of synthetically useful 4‐substituted aminocyclohexanes was consequentially synthesized through biocatalysis, analyzed and stereochemically characterized.

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“…The transamination-reaction can be carried out as a kinetic resolution of a racemic amine or an asymmetric synthesis from the respective prochiral ketone. [22][23][24][25][26][27][28][29][30] Such techniques its reaction solution as a barely soluble salt effectively yields a displacement of the reaction equilibrium towards the products and facilitates a simple downstream processing approach via filtration. [16] Unfortunately, thermodynamic limitations and certain product inhibitions tend to limit the applicability of transaminases in asymmetric synthesis, which needs to be overcome for synthetic purposes.…”

Section: Introductionmentioning

confidence: 99%

Development of an in situ‐Product Crystallization (ISPC)‐Concept to Shift the Reaction Equilibria of Selected Amine Transaminase‐Catalyzed Reactions

Hülsewede

Tänzler

Süss³

et al. 2018

Eur J Org Chem

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The synthesis of enantiopure amines via amine transaminases involves several challenges including unfavorable reaction equilibria and product inhibition. Described here is a non‐catalytic approach to overcome such problems by using an in situ‐product crystallization (ISPC) to selectively remove a targeted product amine from an amine transaminase‐catalyzed reaction. The continuous removal of the product amine from its reaction solution as a barely soluble salt effectively yields a displacement of the reaction equilibrium towards the products and facilitates a simple downstream processing approach via filtration. The targeted product amine is eventually obtained from the salt, while the counterion compound can be easily recycled.

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Asymmetric synthesis of chiral amine in organic solvent and in-situ product recovery for process intensification: A case study

Cited by 18 publications

References 21 publications

Three‐liquid‐phase Spinning Reactor for the Transaminase‐catalyzed Synthesis and Recovery of a Chiral Amine

Three‐liquid‐phase Spinning Reactor for the Transaminase‐catalyzed Synthesis and Recovery of a Chiral Amine

Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates

Development of an in situ‐Product Crystallization (ISPC)‐Concept to Shift the Reaction Equilibria of Selected Amine Transaminase‐Catalyzed Reactions

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