Chiral synthesis of 3-amino-1-phenylbutane by a multi-enzymatic cascade system
Alcover Fortuny, Natàlia (Universitat Autònoma de Barcelona. Departament de Química)
Álvaro, Gregorio (Universitat Autònoma de Barcelona. Departament de Química)
Guillén, Marina (Universitat Autònoma de Barcelona. Departament de Química)

Data:	2021
Resum:	Asymmetric synthesis of chiral amines from prochiral ketones using transaminases is an attractive biocatalytic strategy. Nevertheless, it is hampered by its unfavorable thermodynamic equilibrium. In the present work, an insitu by-product removal strategy was applied for the synthesis of 3-amino-1-phenylbutane (3-APB) by coupling a transaminase with a pyruvate decarboxylase (PDC), which does not require the use of any expensive additional cofactor. Using this strategy, the pyruvate obtained in the transamination reaction is transformed by PDC into acetaldehyde and CO2 which are of high volatility. Two different transaminases from Chromobacterium violaceum (CviTA) and Vibrio fluvialis (VflTA) were characterized to find out the appropriate pH conditions. In both cases, the addition of PDC dramatically enhanced 3-APB synthesis. Afterwards, different reaction conditions were tested to improve reaction conversion and yield. It was concluded that 30 °C and a 20-fold alanine excess lead to the best process metrics. Under the mentioned conditions, yields higher than 60% were reached with nearly 90% selectivity using both CviTA and VflTA. Moreover, high stereoselectivity for (S)-3-APB was obtained and ee of around 90% was achieved in both cases. For the first time, the asymmetric synthesis of 3-APB using PDC as by-product removal system using CviTA is reported.
Ajuts:	Ministerio de Economía y Competitividad BES-2015-072542 Ministerio de Economía y Competitividad CTQ2014-53114R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1462
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Chiral amine ; Transaminase ; Pyruvate decarboxylase (PDC) ; Multi-enzymatic system
Publicat a:	Catalysts, Vol. 11, Issue 8 (August 2021) , art. 973, ISSN 2073-4344

DOI: 10.3390/catal11080973

13 p, 1.6 MB

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