Application of novel High Molecular Weight amine donors in chiral amine synthesis facilitates integrated downstream processing and provides in situ product recovery opportunities

Matassa, Claudia; Ormerod, Dominic; Bornscheuer, Uwe T.; Höhne, Matthias; Satyawali, Yamini

doi:10.1016/j.procbio.2019.02.018

Cited by 8 publications

(16 citation statements)

References 34 publications

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“…Besides the use of an excess of amine donor (AD), methods such as co‐product or product cyclization or polymerization, evaporation of the volatile co‐product and enzymatic cascades for co‐product removal have been developed. Membrane‐assisted techniques for in situ product removal have been also investigated . 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.…”

Section: Figurementioning

confidence: 99%

“…We have previously demonstrated the feasibility of performing the asymmetric synthesis of ( S )‐1‐methyl‐3‐phenylpropylamine using high molecular weight (HMW) donor amines in aqueous, organic solvent and solvent‐free media . With a molecular weight (MW) between 400 and 1500 g/mol, these large molecules were effectively retained by commercial nanofiltration membranes, when employed in an aqueous environment . Transamination using HMW ADs was also performed in the presence of a non‐polar organic solvent ( n ‐heptane).…”

Section: Figurementioning

confidence: 99%

“…Transamination using HMW ADs was also performed in the presence of a non‐polar organic solvent ( n ‐heptane). Specifically, the HMW AD Jeffamine ED‐600 (MW of 600 g/mol), commercialized by Huntsman corporation, was insoluble in n‐heptane, thus, resulting in a two‐liquid‐phase system . Coupling the two‐liquid phase reaction system with membrane‐assisted product extraction, the reaction equilibrium was successfully shifted to reach 60 % conversion compared to 15 % without product extraction.…”

Section: Figurementioning

confidence: 99%

“…Based on the previous studies, 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 .…”

Section: Figurementioning

confidence: 99%

“…The first transaminase‐mediated synthesis combined with continuous product recovery was performed employing the same configuration of the preliminary partitioning experiment (Figure , configuration 1). Having already proven in our recent work the reproducibility of the reaction system, a single experiment at 1L scale was carried out. Out of 5 g of ketone substrate, initially added in n ‐heptane, only 0.8 g of MPPA was extracted and isolated after 17 days operation (Figure ).…”

Section: Figurementioning

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: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

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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The Role of Buffer, Pyridoxal 5’‐Phosphate and Light on the Stability of the Silicibacter Pomeroyi Transaminase

Merz

Langen²,

Berglund

2022

ChemCatChem

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Transaminases are pyridoxal 5'-phosphate (PLP)-dependent enzymes that transfer amino-functions. The transaminase from Silicibacter pomeroyi (SpATA) exhibits a broad substrate spectrum. In this work we examined the effect of different conditions (light, buffer and PLP-concentration) on the stability of SpATA, as well as the causes for these effects. The enzyme was stored either in TRIS or CHES with 0-10 mM added PLP at 22 °C. The samples were either kept dark or they were exposed to light. The results show that invariably, all samples kept in darkness exhibited longer half-life times than the ones exposed to light. An increase in the half-life from 8 h to 720 h could be achieved solely by keeping the sample dark. Especially samples in CHES buffer inactivated faster in light the more PLP was present, due to the degradation of PLP. In TRIS however, an imine-bond between TRIS and PLP protects PLP from degradation.

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Continuous Preparative Application of Amine Transaminase‐Catalyzed Reactions with Integrated Crystallization

Tiedemann,

Neuburger,

Gazizova

et al. 2024

Eur J Org Chem

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Transaminases are valuable catalysts in the synthesis of chiral amines. However, secondary techniques are typically required to shift the reaction equilibrium to the product side. This study focuses on the in situ‐product crystallization, specifically at preparative synthetic scale as a non‐synthetic tool for a selection of aromatic and aliphatic substrates using the transaminase from Silicibacter pomeroyi. Herein the technique is implemented in a simplified manner to facilitate in situ‐product removal and downstream‐processing in a combined crystallization step. After a series of optimizations, product concentrations of >0.9 mol/L and >99% e.e.(S) were obtained implementing a repetitive batch reaction approach using a universal carboxylate as anion.

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Application of novel High Molecular Weight amine donors in chiral amine synthesis facilitates integrated downstream processing and provides in situ product recovery opportunities

Cited by 8 publications

References 34 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

The Role of Buffer, Pyridoxal 5’‐Phosphate and Light on the Stability of the Silicibacter Pomeroyi Transaminase

Continuous Preparative Application of Amine Transaminase‐Catalyzed Reactions with Integrated Crystallization

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