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.

cib GmbH Krenngasse 37 8010 Graz Austria

Institute of Applied Synthetic Chemistry TU Wien Getreidemarkt 9 OC 163 A 1060 Vienna Austria

Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 CZ 142 20 Prague Czech Republic

Institute of Molecular Biotechnology Graz University of Technology Petersgasse 14 A 8010 Graz Austria

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Aldoxime dehydratases: production, immobilization, and use in multistep processes

Bio-Based Valorization of Lignin-Derived Phenolic Compounds: A Review