Enantioselective One-Pot Synthesis of Biaryl-Substituted Amines by Combining Palladium and Enzyme Catalysis in Deep Eutectic Solvents

Paris, Juraj; Telzerow, Aline; Ríos‐Lombardía, Nicolás; Steiner, Kerstin; Schwab, Helmut; Morís, Francisco; Gröger, Harald; González‐Sabín, Javier

doi:10.1021/acssuschemeng.8b06715

Cited by 53 publications

(44 citation statements)

References 60 publications

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“…DMSO is a commonly applied co‐solvent in biocatalysis when the solubility of hydrophobic substrates needs to be increased and it is one of the best tolerated co‐solvents for various enzyme types, as recently demonstrated in a systematic stability study involving eight common water‐miscible organic solvents . Other examples of co‐solvents applied in ATA‐catalyzed reactions include 1,2‐dimethoxyethane for solubilization of steroids and deep eutectic solvents for synthesis of biaryl amines . The influence of DMSO on the transamination of ( S )‐1‐phenylethylamine and pyruvate was previously reported for Cv ‐ATA WT .…”

Section: Resultsmentioning

confidence: 99%

Engineering the Active Site of an (S)‐Selective Amine Transaminase for Acceptance of Doubly Bulky Primary Amines

et al. 2019

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A protein engineering approach for expanding the substrate scope of the (S)‐selective Chromobacterium violaceum amine transaminase is presented. Amino acid residues in the small binding pocket of the active site were targeted in order to increase the pocket size for acceptance of primary amines bearing two bulky groups. A highly sensitive fluorescence assay was then used to evaluate the generated enzyme variants for their activity towards propyl‐ and benzyl‐substituted screening substrates. The best variant, L59A/F88A, was successfully applied in the kinetic resolution of 1,2‐diphenylethylamine using different conditions and substrate loadings. The variant L59A/F88A generated enantiomerically pure (R)‐1,2‐diphenylethylamine with ee>99% under all tested conditions. The variant also holds great promise for synthesis of hydrophobic compounds as it shows optimum activity when 20‐30% (v/v) DMSO is applied as cosolvent. The variant L59A/F88A provides a great addition to the available catalyst toolbox for synthesis of chiral amines, as it is the first published (S)‐selective amine transaminase showing activity towards benzyl‐substituted primary amines.

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Section: Resultsmentioning

confidence: 99%

Engineering the Active Site of an (S)‐Selective Amine Transaminase for Acceptance of Doubly Bulky Primary Amines

et al. 2019

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“…A eutectic mixture of ChCl and glycerol (Gly) (1:2 mol mol −1 ), which is also known as glyceline, was selected as a prototypical DES for ADH‐catalyzed reactions. Glyceline is one of the most successfully applied DESs for biocatalysis . MD simulations focus on the quantitative analysis of protein flexibility and hydration level, whereby the results from enzymatic activity and stability are correlated and explained.…”

Section: Introductionmentioning

confidence: 98%

“…Moreover, DESs display beneficial effects, or even stereoinversion, on the enantioselectivity of bioreduction catalyzed by baker's yeast cells . Some isolated enzymes (mainly ADHs) also show good performance and the ability to be combined with metal catalysts in DESs . However, a rational evaluation of the effect of DESs, as non‐conventional media, on the behavior of oxidoreductases is still missing.…”

Section: Introductionmentioning

confidence: 99%

Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

Huang

Bittner

Marı́a³

et al. 2019

ChemBioChem

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The use of oxidoreductases (EC1) in non‐conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in‐depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (aW) in non‐conventional media. At low aW values (<0.2), ADH does not show any activity; at higher aW values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.

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“…Further, the cascade was implemented in a flow continuous system by means of the enzyme immobilization with a metal affinity resin (EziG TM ) employing identical reaction media for each step that in the batch reaction setup (Entry 6). Soon after, an identical cascade with EX‐ωTA was reported in a reaction medium consisting of a DES‐buffer mixture (Entry 7) . In fact, this was the first report of ATAs in these neoteric solvents and 1ChCl/2Gly turned out to be the only co‐solvent compatible for both steps due to inhibition of Pd and EX‐ωTA catalysts.…”

Section: Chemoenzymatic Synthetic Cascadesmentioning

confidence: 78%

Non‐Conventional Media as Strategy to Overcome the Solvent Dilemma in Chemoenzymatic Tandem Catalysis

Kourist

González‐Sabín

2020

ChemCatChem

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The amazing potential of multi‐catalytic cascade reactions to reduce the number of reaction steps and to solve synthetic problems brings the challenge of an increasing complexity that must be controlled. Particularly chemo‐enzymatic reactions are prone to conflicts regarding different optimal reaction conditions for chemical and biological catalysts. The preference of many chemical catalysts for hydrophobic (and often water‐free) solvent and of many enzymes for water poses a solvent dilemma. Recently, non‐conventional solvents have been very successful to provide suitable reaction media for catalysts that otherwise require very different solvents, and to alleviate fundamental problems such as the low solubility of many substrates in aqueous solvents. In the last few years, several examples underlined the considerable potential of ionic liquids and deep eutectic solvents for the engineering of cascade reactions. This mini‐review showcases the recent developments on the implementation of the so‐called non‐conventional media in such processes.

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Enantioselective One-Pot Synthesis of Biaryl-Substituted Amines by Combining Palladium and Enzyme Catalysis in Deep Eutectic Solvents

Cited by 53 publications

References 60 publications

Engineering the Active Site of an (S)‐Selective Amine Transaminase for Acceptance of Doubly Bulky Primary Amines

Engineering the Active Site of an (S)‐Selective Amine Transaminase for Acceptance of Doubly Bulky Primary Amines

Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

Non‐Conventional Media as Strategy to Overcome the Solvent Dilemma in Chemoenzymatic Tandem Catalysis

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