Scalability of U-Shape Magnetic Nanoparticles-Based Microreactor–Lipase-Catalyzed Preparative Scale Kinetic Resolutions of Drug-like Fragments

• Published in: Catalysts
• Main Authors: Fausto M. W. G. Silva, Ali O. Imarah, Orsolya Takács, László Tuba, László Poppe
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2023
• Subjects: magnetic nanoparticles; flow biocatalysis; lipase; kinetic resolution; microreactor; chiral 3D N -heterocycle; Chemical technology; TP1-1185; Chemistry; QD1-999; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/catal13020384; https://doaj.org/article/f61c019a32ae4ddabd4689698a7f782b

The production of active pharmaceutical ingredients (APIs) and fine chemicals is accelerating due to the advent of novel microreactors and new materials for immobilizing customized biocatalysts that permit long-term use in continuous-flow reactors. This work studied the scalability of a tunable U-shape magnetic nanoparticles (MNPs)-based microreactor. The reactor consisted of a polytetrafluoroethylene tube (PTFE) of various inner diameters (ID = 0.75 mm, 1.50 mm, or 2.15 mm) and six movable permanent magnets positioned under the tube to create reaction chambers allowing the fluid reaction mixture to flow through and above the enzyme-loaded MNPs anchored by permanent magnets. The microreactors with various tube sizes and MNP capacities were tested with the preparative scale kinetic resolution of the drug-like alcohols 4-(3,4-dihydroisoquinolin-2(1 H )-yl)butan-2-ol (±)- 1a and 4-(3,4-dihydroquinolin-1(2 H )-yl)butan-2-ol (±)- 1b, utilizing Lipase B from Candida antarctica immobilized covalently onto MNPs, leading to highly enantioenriched products [( R )- 2a,b and ( S )- 1a,b ]. The results in the U-shape MNP flow reactor were compared with reactions in the batch mode with CaLB-MNPs using similar conditions. Of the three different systems, the one with ID = 1.50 mm showed the best balance between the maximum loading capacity of biocatalysts in the reactor and the most effective cross-section area. The results showed that this U-shaped tubular microreactor might be a simple and flexible instrument for many processes in biocatalysis, providing an easy-to-set-up alternative to existing techniques.