engleski

Biocatalytic synthesis of enantiopure fluorinated building blocks: discovering the bottlenecks by enzyme reaction engineering approach

Optically pure fluorinated organic azides represent synthetically valuable building blocks in a range of industrial applications. Since the direct fluorination of molecules is challenging from both economic and environmental perspective, the development of novel methods for modifying existing fluorinated synthons is highly desirable. In this work, enantioselective azidolysis of fluorinated aromatic epoxides catalyzed by halohydrin dehalogenase (HHDH) was explored. A series of 11 fluorinated epoxides were evaluated as substrates from the viewpoint of hydrolytic stability and enzyme kinetics. Synthesis of enantiopure (R)-2-azido-1-[4-(trifluoromethyl)phenyl]ethanol with HheC-W249P variant was selected for detailed kinetic investigation. Reaction bottlenecks were identified. Epoxide hydrolysis, enzyme inhibitions and operational stability decay were found to undesirably affect the reaction outcome. Understanding the kinetic limitations and applying model-based process simulations enabled the selection of reactor type and initial conditions favoring biotransformation. By selecting a repetitive batch reactor set-up, the reaction yield of 95% could be obtained, together with the increase in the reaction selectivity of 100% compared to the batch reactor. This poster was funded by Croatian Science Foundation (IP-2018-01-4493).

Fluorinated building blocks ; Halohydrin dehalogenase ; Enzyme kinetics ; Mathematical modelling ; Reaction engineering ; Reaction bottlenecks

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