Chloroperoxidase-catalyzed aminoalcohol oxidation : substrate specificity and novel strategy for the synthesis of N-Cbz-3-aminopropanal
Masdeu, Gerard (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Pérez-Trujillo, Míriam (Universitat Autònoma de Barcelona. Servei de Ressonància Magnètica Nuclear)
López Santín, Josep (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Álvaro, Gregorio (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Data:	2016
Resum:	The ability of chloroperoxidase (CPO) to catalyze amino alcohol oxidations was investigated. The oxidations of compounds with different configurations with respect to the amine position towards hydroxyl - using H₂O₂ and tert-butyl hydroperoxide (t-BuOOH) - were analyzed in terms of the initial reaction rate, substrate conversion, and CPO operational stability. It was observed that the further the amino group from the hydroxyl, the lower the initial reaction rate. The effect of the amino-protecting group and other substituents (i. e. , methyl and hydroxyl) was also examined, revealing an increase in steric hindrance due to the effect of bulky substituents. The observed reaction rates were higher with t-BuOOH, whereas CPO was more stable with H₂O₂. Moreover, CPO stability had to be determined case by case as the enzyme activity was modulated by the substrate. The oxidation of N-Cbz-3-aminopropanol (Cbz, carboxybenzyl) to N-Cbz-3-aminopropanal was investigated. Main operational conditions such as the reaction medium, initial amino alcohol concentration, and peroxide nature were studied. The reaction kinetics was determined, and no substrate inhibition was observed. By-products from a chemical reaction between the formed amino aldehyde and the peroxide were identified, and a novel reaction mechanism was proposed. Finally, the biotransformation was achieved by reducing side reactions and identifying the key factors to be addressed to further optimize the product yield.
Ajuts:	Ministerio de Economía y Competitividad CTQ2014-53114R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-452
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Chloroperoxidase (CPO) ; Amino alcohol oxidation ; Substrate specificity for chloroperoxidase ; N-Cbz-3-aminopropanal synthesis ; Aldehyde-peroxide reaction ; D-Fagomine precursor
Publicat a:	Process biochemistry, Vol. 51, issue 9 (Sep. 2016) , p. 1204-1211, ISSN 1873-3298

DOI: 10.1016/j.procbio.2016.05.022

Post-print 25 p, 1.6 MB

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