Abstract
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.
Highlights
L-Alanine 200 mM, potassium phosphate buffer 150 mM, 25% v·v−1 pyruvate decarboxylase (PDC) (30 U·mL−1), 5% v v−1 amounts of 3-APB (Figure S1). These results suggested that the TA-PDC coupling favors transaminase, 1 mM pyridoxal-5′-phospate (PLP), 0.1 mM thiamine pyrophosphate (TPP), and 0.1 an equilibrium shifting towards amine formation
Synthesis of 3-APB Catalyzed by TA and PDC
3-APB synthesis catalyzed by CviTA and+VflTA was deeply studied
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chiral amines are target molecules of high industrial interest. These molecules are useful as intermediates and building blocks in pharmaceutical synthesis (e.g., for the production of codeine, morphine, and tropane alkaloids), as ligands in various asymmetric transformations, as chiral ligands in metal-complex catalysis, as chiral auxiliaries and resolving agents, and in agrochemical industries [1,2,3,4,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
