scholarly journals Enantioselective Transamination in Continuous Flow Mode with Transaminase Immobilized in a Macrocellular Silica Monolith

2017 ◽  
Author(s):  
Ludivine van den Biggelaar ◽  
Patrice Soumillion ◽  
Damien P. Debecker
Keyword(s):  
Continuous Flow ◽  
Preferential Flow ◽  
Kinetic Resolution ◽  
Flow Reactor ◽  
Sol Gel ◽  
Flow Mode ◽  
Chiral Amine ◽  
Silica Monoliths ◽  
Covalent Grafting ◽  
Heterogeneous Biocatalysts

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

scholarly journals Enantioselective Transamination in Continuous Flow Mode with Transaminase Immobilized in a Macrocellular Silica Monolith

2017 ◽  
Author(s):  
Ludivine van den Biggelaar ◽  
Patrice Soumillion ◽  
Damien P. Debecker
Keyword(s):  
Continuous Flow ◽  
Preferential Flow ◽  
Kinetic Resolution ◽  
Flow Reactor ◽  
Sol Gel ◽  
Flow Mode ◽  
Chiral Amine ◽  
Silica Monoliths ◽  
Covalent Grafting ◽  
Heterogeneous Biocatalysts

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion-templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

scholarly journals Immobilized Whole-Cell Transaminase Biocatalysts for Continuous-Flow Kinetic Resolution of Amines

Catalysts ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 438 ◽  
Author(s):  
Zsófia Molnár ◽  
Emese Farkas ◽  
Ágnes Lakó ◽  
Balázs Erdélyi ◽  
Wolfgang Kroutil ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Kinetic Resolution ◽  
Sol Gel ◽  
Chiral Amines ◽  
Flow Mode ◽  
Immobilized Cell ◽  
Hollow Silica ◽  
E Coli ◽  
Sol Gel Process ◽  
Racemic Amines

Immobilization of transaminases creates promising biocatalysts for production of chiral amines in batch or continuous-flow mode reactions. E. coli cells containing overexpressed transaminases of various selectivities and hollow silica microspheres as supporting agent were immobilized by an improved sol-gel process to produce immobilized transaminase biocatalysts with suitable stability and mechanical properties for continuous-flow applications. The immobilized cell-based transaminase biocatalyst proved to be durable and easy-to-use in kinetic resolution of four racemic amines 1a–d. The batch and continuous-flow mode kinetic resolutions with transaminase biocatalyst of opposite stereopreference provided access to both enantiomers of the corresponding amines. By using the most suitable immobilized transaminase biocatalysts, this study describes the first transaminase-based approach for the production of both pure enantiomers of 1-(3,4-dimethoxyphenyl)ethan-1-amine 1d.

Continuous Flow Mode Biocatalytic Transamination Using Macrocellular Silica Monoliths: Optimizing Support Functionalisation and Enzyme Grafting

2019 ◽  
Author(s):  
Ludivine van den Biggelaar ◽  
Patrice Soumillion ◽  
Damien Debecker
Keyword(s):  
Enzyme Immobilization ◽  
Continuous Flow ◽  
Sol Gel ◽  
Fold Increase ◽  
Covalent Attachment ◽  
Flow Mode ◽  
Active Materials ◽  
Silica Monoliths ◽  
Transamination Reaction ◽  
Reported Data

<div>Transaminases are immobilized onto macrocellular silica monoliths and used for carrying a continuous flow mode transamination reaction. Monoliths were prepared via an emulsion-templated sol-gel method and functionalized by amino-moieties (APTES) in order to covalently immobilize the enzymes, using glutaraldehyde as a cross-linking agent. In order to obtain higher performance and improved reproducibility, we investigate the key parameters of APTES functionalization and of enzyme grafting. Four functionalization protocols were studied. It is shown that controlling the moisture levels in monolith and in the functionalisation solution led to a 3-fold increase in activity as compared to the previously reported data, and greatly improved the reproducibility. Additionally, we report a strong beneficial effect of running the enzyme immobilization at room temperature instead of 4°C, further enhancing the obtained activity. Finally, the popular method which consists in stabilizing the covalent attachment of the enzyme by reducing the imine bonds formed between the enzyme and the functionalized surface was investigated. We highlight a strong enzyme deactivation caused by cyanoborohydride, making this strategy irrelevant in this case. All in all, the improvements presented here for enzyme immobilization in macrocellular silica monoliths, lead to the preparation of more active materials for continuous flow mode biocatalysis.<br></div>

Continuous Flow Mode Biocatalytic Transamination Using Macrocellular Silica Monoliths: Optimizing Support Functionalisation and Enzyme Grafting

2019 ◽  
Author(s):  
Ludivine van den Biggelaar ◽  
Patrice Soumillion ◽  
Damien Debecker
Keyword(s):  
Enzyme Immobilization ◽  
Continuous Flow ◽  
Sol Gel ◽  
Fold Increase ◽  
Covalent Attachment ◽  
Flow Mode ◽  
Active Materials ◽  
Silica Monoliths ◽  
Transamination Reaction ◽  
Reported Data

<div>Transaminases are immobilized onto macrocellular silica monoliths and used for carrying a continuous flow mode transamination reaction. Monoliths were prepared via an emulsion-templated sol-gel method and functionalized by amino-moieties (APTES) in order to covalently immobilize the enzymes, using glutaraldehyde as a cross-linking agent. In order to obtain higher performance and improved reproducibility, we investigate the key parameters of APTES functionalization and of enzyme grafting. Four functionalization protocols were studied. It is shown that controlling the moisture levels in monolith and in the functionalisation solution led to a 3-fold increase in activity as compared to the previously reported data, and greatly improved the reproducibility. Additionally, we report a strong beneficial effect of running the enzyme immobilization at room temperature instead of 4°C, further enhancing the obtained activity. Finally, the popular method which consists in stabilizing the covalent attachment of the enzyme by reducing the imine bonds formed between the enzyme and the functionalized surface was investigated. We highlight a strong enzyme deactivation caused by cyanoborohydride, making this strategy irrelevant in this case. All in all, the improvements presented here for enzyme immobilization in macrocellular silica monoliths, lead to the preparation of more active materials for continuous flow mode biocatalysis.<br></div>

scholarly journals Mass Transfer in Hierarchical Silica Monoliths Loaded With Pt in the Continuous-Flow Liquid-Phase Hydrogenation of p-Nitrophenol

2021 ◽  
Vol 3 ◽  
Author(s):  
Haseeb Ullah Khan Jatoi ◽  
Michael Goepel ◽  
David Poppitz ◽  
Richard Kohns ◽  
Dirk Enke ◽  
...  
Keyword(s):  
Mass Transfer ◽  
Flow Rate ◽  
Continuous Flow ◽  
Flow Reactor ◽  
Sol Gel ◽  
Catalyst Support ◽  
Test Reaction ◽  
Silica Monoliths ◽  
Monolithic Catalysts ◽  
Liquid Phase Hydrogenation

Sol-gel-based silica monoliths with hierarchical mesopores/macropores are promising catalyst support and flow reactors. Here, we report the successful preparation of cylindrically shaped Pt-loaded silica monoliths (length: 2 cm, diameter: 0.5 cm) with a variable mean macropore width of 1, 6, 10, or 27 μm at a fixed mean mesopore width of 17 nm. The Pt-loaded monolithic catalysts were housed in a robust cladding made of borosilicate glass for use as a flow reactor. The monolithic reactors exhibit a permeability as high as 2 μm2 with a pressure drop below 9 bars over a flow rate range of 2–20 cm3 min−1 (solvent: water). The aqueous-phase hydrogenation of p-nitrophenol to p-aminophenol with NaBH4 as a reducing agent was used as a test reaction to study the influence of mass transfer on catalytic activity in continuous flow. No influence of flow rate on conversion at a fixed contact time of 2.6 s was observed for monolithic catalysts with mean macropore widths of 1, 10, or 27 µm. As opposed to earlier studies conducted at much lower flow velocities, this strongly indicates the absence of external mass-transfer limitations or stagnant layer formation in the macropores of the monolithic catalysts.

scholarly journals Tailored sol–gel immobilized lipase preparates for the enzymatic kinetic resolution of heteroaromatic alcohols in batch and continuous flow systems

RSC Advances ◽  
2017 ◽  
Vol 7 (83) ◽  
pp. 52977-52987 ◽  
Author(s):  
Mădălina Elena Moisă ◽  
Cristina Georgiana Spelmezan ◽  
Cristina Paul ◽  
Judith Hajnal Bartha-Vári ◽  
László Csaba Bencze ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Kinetic Resolution ◽  
Immobilized Lipase ◽  
Sol Gel ◽  
Flow Mode ◽  
Batch Mode ◽  
Flow Reactors ◽  
Immobilized Lipases ◽  
Enzymatic Kinetic Resolution ◽  
Continuous Flow Reactors

The EKR of some heteroaromatic secondary ethanols with tailored sol–gel immobilized lipases in batch and continuous-flow reactors was studied. The productivity in continuous-flow mode is higher than in batch mode.

Chemoenzymatic Dynamic Kinetic Resolution of Amines in Fully Continuous-Flow Mode

2018 ◽  
Vol 20 (24) ◽  
pp. 8052-8056 ◽  
Author(s):  
Emese Farkas ◽  
Márk Oláh ◽  
Attila Földi ◽  
János Kóti ◽  
János Éles ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Kinetic Resolution ◽  
Flow Mode ◽  
Dynamic Kinetic Resolution

scholarly journals Continuous Flow Friedel–Crafts Alkylation Catalyzed by Silica Supported Phosphotungstic Acid: An Environmentally Benign Process

2021 ◽  
Author(s):  
Zsófia Császár ◽  
Tatjána Juzsakova ◽  
Miklós Jakab ◽  
Szabolcs Balogh ◽  
Ágnes Szegedi ◽  
...  
Keyword(s):  
Flow Rate ◽  
Continuous Flow ◽  
Phosphotungstic Acid ◽  
Flow Reactor ◽  
Analytical Techniques ◽  
Catalyst System ◽  
Molar Ratio ◽  
Flow Mode ◽  
Reaction Conditions ◽  
Composite Catalysts

AbstractSix silica-supported phosphotungstic acid catalysts (PTA/SiO2) of different composition (20–70 wt% PTA content) have been synthesized and characterized by elemental analysis, BET, BJH, NH3-TPD methods, FT-IR spectroscopy of adsorbed pyridine and 1H MAS NMR techniques. The new composite catalysts were first applied in the Friedel–Crafts alkylation of toluene with 1-octene as a benchmark process under batch conditions in order to screen their activity and recyclability. The combined analytical techniques together with the catalytic studies enabled the identification of the main factors affecting the activity of the catalysts. Based on these preliminary experiments, the best performing catalyst system (50 wt% PTA/SiO2) was investigated in continuous flow mode using an in-house-made flow reactor. The thorough screening of the reaction conditions (temperature, toluene/1-octene molar ratio and flow rate) provided firm evidence that the 50 wt% PTA/SiO2 composite is highly active, selective and stable catalyst under mild reaction conditions even at elevated flow rate. Additionally, the catalyst used in the flow mode could successfully be regenerated and reused in the alkylation process.

scholarly journals Lipase B from Candida antarctica Immobilized on Epoxy-functionalized Hollow Silica Microspheres: Efficient Biocatalysts for Enantiomer Selective Acylation of Alcohols and Amines

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Márk Oláh ◽  
Szandra Suba ◽  
Zoltán Boros ◽  
Péter Kovács ◽  
Mathilde Gosselin ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Kinetic Resolution ◽  
Operation Time ◽  
Candida Antarctica ◽  
Effect Of Temperature ◽  
Flow Mode ◽  
Silica Microspheres ◽  
Lipase B ◽  
Hollow Silica ◽  
Racemic Amines

Hollow silica microspheres with promising physical properties (MAT540TM) as support for enzyme immobilization and biocatalyst were investigated in this study. The amine-functionalized MAT540TM was activated by six bisepoxides inclosing different spacers and used as epoxy-functionalized carrier for immobilization of lipase B from Candida antarctica (CaLB). The novel, covalently fixed CaLB biocatalysts were compared in kinetic resolution (KR) of racemic 1-phenyethanol rac-1 and five racemic amines rac-3a-e using shaken flasks and continuous-flow packed-bed microreactors. Mechanic stability, re-usability and the effect of temperature (0–90 °C) on productivity and enantiomer selectivity of the covalently immobilized CaLB were investigated. The best performing CaLB biocatalyst showed good mechanic stability after 24 h operation time in continuous-flow mode at 60 °C and provided in KRs of racemic 1-phenyethanol rac-1 with vinyl acetate and of five racemic amines with isopropyl 2-ethoxyacetate as acylating agent the non-reacted (S)-alcohol [(S)-1] or (S)-amines [(S)-3a-e] and the forming (R)-ester [(R)-2] or (R)-amide [(R)-4a-e] in good yields with high enantiomeric excess (ee > 99 %, for all).

Intensification of Free-Radical Racemization for a Non-activated Amine in a Continuous Flow Reactor

Synthesis ◽  
2020 ◽  
Vol 52 (22) ◽  
pp. 3389-3396
Author(s):  
Frédéric C. Toussaint ◽  
Thierry Defrance ◽  
Serge Decouvreur ◽  
Nicolas Carly ◽  
Alain Merschaert
Keyword(s):  
Free Radical ◽  
Pharmaceutical Industry ◽  
Chiral Separation ◽  
Process Design ◽  
Continuous Flow ◽  
Flow Reactor ◽  
Flow Mode ◽  
Environmental Footprint ◽  
Radical Initiator ◽  
Continuous Flow Reactor

The free-radical racemization of non-activated amines is a powerful tool for process design in the pharmaceutical industry, allowing the recycling of undesired enantiomers after chiral separation. This paper describes the development of the free-radical racemization of a key API intermediate in a continuous flow reactor. Upon development, a significant reduction of the solvent usage and radical initiator was made possible thanks to the conversion into a continuous flow mode. This intensification positively impacted both the environmental footprint and the safety of the reaction as well as maintaining satisfactory productivity.

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