title: Toluene Dioxygenase-Catalysed Oxidation of Benzyl Azide to Benzonitrile: Mechanistic Insights for an Unprecedented Enzymatic Transformation.
abstract: Enzymatic dioxygenation of benzyl azide by toluene dioxygenase (TDO) produces significant amounts of the cis-cyclohexadienediol derived from benzonitrile, along with the expected azido diols. We demonstrate that TDO catalyses the oxidation of benzyl azide to benzonitrile, which is further dioxygenated to produce the observed cis-diol. A proposed mechanism for this transformation involves initial benzylic monooxygenation followed by a nitrene-mediated rearrangement to form an oxime, which is further dehydrated to afford the nitrile. To the best of our knowledge, this is the first report of enzymatic oxidation of an alkyl azide to a nitrile. In addition, the described oxime-dehydration activity has not been reported for Rieske dioxygenases.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay.
authors.forename: María Agustina
authors.initials: MA
authors.lastname: Vila
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay.
authors.forename: Mariana
authors.initials: M
authors.lastname: Pazos
authors.affiliation: Cátedra de Microbiología, Departamento de Biociencias, Facultad de Química, Universidad de la República, Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay.
authors.forename: César
authors.initials: C
authors.lastname: Iglesias
authors.affiliation: Cátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República., Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Veiga
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Seoane
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av. General Flores 2124, C.P. 11800, Montevideo, Uruguay. icarrera@fq.edu.uy.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Carrera
mesh_terms: D001386:Azides / Q000737:chemistry / Q000378:metabolism*; D001593:Benzyl Compounds / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D016958:Pseudomonas putida / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
chemical_list: D001386:Azides; D001593:Benzyl Compounds; D009570:Nitriles; C014356:benzonitrile; D010105:Oxygenases; C023172:toluene dioxygenase
keywords: Rieske; azides; biocatalysis; dioxygenases; oxidation