Chemoenzymatic one-pot reaction from carboxylic acid to nitrile <i>via</i> oxime

Horvat, Melissa; Weilch, Victoria; Rädisch, Robert; Hecko, Sebastian; Schiefer, Astrid; Rudroff, Florian; Wilding, Birgit; Klempier, Norbert; Pátek, Miroslav; Martı́nková, Ludmila; Winkler, Margit

doi:10.1039/d1cy01694f

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…In addition to co‐expression of CARs with further enzymes in a single culture, [74] the combination of separate cultures in biotransformations allows for utmost flexibility in terms of achievable products: The Turner group is exploring this strategy for the synthesis of various amines by combining CARs with imine reductases, [63] transaminases [29] and reductive aminases [75] . Chemical trapping of aldehydes to oximes and their subsequent enzymatic dehydration using mixed cultures is a new strategy for cyanide free nitrile synthesis [76] …”

Section: The Substrate Scope Of Cars and Other Atr‐proteinsmentioning

confidence: 99%

“…Chemical trapping of aldehydes to oximes and their subsequent enzymatic dehydration using mixed cultures is a new strategy for cyanide free nitrile synthesis. [76] CARs may also be exploited in cell free syntheses: The required systems for the recycling of NADPH and ATP in vitro were successfully implemented [77,78] and first examples of aldehyde synthesis on preparative scale are emerging, [79] even with commercial enzyme preparations. [35,80] This shows that enzymatic carboxylate reduction could become a standard tool in chemistry labs in the near future (Scheme 2).…”

Section: Chemcatchemmentioning

confidence: 99%

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Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Winkler

Ling

2022

ChemCatChem

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Carboxylate reductases (CARs) are valuable catalysts for the selective one‐step reduction of carboxylic acids to their corresponding aldehydes. In recent years, numerous new CARs have been made available, studied and applied in the context of biocatalytic syntheses. The preparation of aldehydes as end products for the flavor and fragrance sector and the integration of CARs in cascade reactions with aldehydes as the key intermediates represent the two major fields of applications. This review gives a comprehensive overview of the current toolbox of recombinant CARs and their numerous carboxylate substrates. Non‐natural functions of CARs are highlighted and recent insight into the structure‐function relationship of CARs are summarized.

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Section: The Substrate Scope Of Cars and Other Atr‐proteinsmentioning

confidence: 99%

Section: Chemcatchemmentioning

confidence: 99%

Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Winkler

Ling

2022

ChemCatChem

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“…We ascribed this effect to inhibition of the CAR by nitriles, because the majority of material was non‐reacted carboxylic acid, which points at a limitation in carboxylate reduction. Nc CAR is inhibited by 7 d in vitro [12] . In addition, ATP supply might be limiting because of effects of nitriles on cell viability.…”

Section: Resultsmentioning

confidence: 99%

Organic Acid to Nitrile: A Chemoenzymatic Three‐Step Route

et al. 2022

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Various widely applied compounds contain cyano-groups, and this functional group serves as a chemical handle for a whole range of different reactions. We report a cyanide free chemoenzymatic cascade for nitrile synthesis. The reaction pathway starts with a reduction of carboxylic acid to aldehyde by carboxylate reductase enzymes (CARs) applied as living cell biocatalysts. The second -chemical -step includes in situ oxime formation with hydroxylamine. The final direct step from oxime to nitrile is catalyzed by aldoxime dehydratases (Oxds). With compatible combinations of a CAR and an Oxd, applied in one-pot two-step reactions, several aliphatic and aryl-aliphatic target nitriles were obtained in more than 80% conversion. Phenylacetonitrile, for example, was prepared in 78% isolated yield. This chemoenzymatic route does not require cyanide salts, toxic metals, or undesired oxidants in contrast to entirely chemical procedures.

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“…[101] The same aldoxime dehydratase may provide access to enantiomerically pure nitriles by starting from the racemic aldoxime mixture of the E-isomer or the Zisomer. [102] Nitriles have been prepared in a chemoenzymatic cascade reaction, applying in the last step aldoxime dehydratase OxdB in whole cells and starting with the aldehyde formation, either from the corresponding alcohols, [103] or from the carboxylic acids, [104] which can be derived from biobased raw materials.…”

Section: Chemsuschemmentioning

confidence: 99%

Selective Biocatalytic Defunctionalization of Raw Materials

Wohlgemuth

2022

ChemSusChem

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Biobased raw materials, such as carbohydrates, amino acids, nucleotides, or lipids contain valuable functional groups with oxygen and nitrogen atoms. An abundance of many functional groups of the same type, such as primary or secondary hydroxy groups in carbohydrates, however, limits the synthetic usefulness if similar reactivities cannot be differentiated. Therefore, selective defunctionalization of highly functionalized biobased starting materials to differentially functionalized compounds can provide a sustainable access to chiral synthons, even in case of products with fewer functional groups. Selective defunctionalization reactions, without affecting other functional groups of the same type, are of fundamental interest for biocatalytic reactions. Controlled biocatalytic defunctionalizations of biobased raw materials are attractive for obtaining valuable platform chemicals and building blocks. The biocatalytic removal of functional groups, an important feature of natural metabolic pathways, can also be utilized in a systemic strategy for sustainable metabolite synthesis.

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Chemoenzymatic one-pot reaction from carboxylic acid to nitrile via oxime

Abstract: We report a new chemoenzymatic cascade starting with aldehyde synthesis by carboxylic acid reductase (CAR) followed by chemical in situ oxime formation. The final step to the nitrile is catalyzed...

Cited by 14 publications

References 39 publications

Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Biocatalytic Carboxylate Reduction – Recent Advances and New Enzymes

Organic Acid to Nitrile: A Chemoenzymatic Three‐Step Route

Selective Biocatalytic Defunctionalization of Raw Materials

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