engleski

Green synthesis of fluorinated optically pure compound

Optically pure compounds are of great significance in the pharmaceutical industry, with the increasing interest in fluorinated derivatives. One important enzyme group employed in synthesizing various chiral building blocks are halohydrin dehalogenases (HHDHs). HHDHs can accept numerous anionic nucleophiles from cyanide, cyanate, thiocyanate to azide and nitrite. In their presence the ring-opening reaction of epoxide occurs, leading to β-substituted alcohol. [1] The foundation of this work lies in a biocatalytic reaction shown in Fig. 1. Mathematical model for the synthesis of (S)-2-(4-fluorophenyl)-3-hydroxypropanenitrile was earlier developed by coupling kinetic equations with mass balances. A series of different batch experiments varying in initial concentrations of epoxide, NaCN and HHDH were conducted with aim of model validation. Enzyme deactivation influenced by initial epoxide concentration was observed within incubation experiments and operational stability decay was mathematically described and included in the model. With the increase in the epoxide concentration, enzyme stability decreased, while the cyanide nucleophile did not have a significant effect on the stability of the enzyme. Experimental data has shown a satisfactory match with an earlier developed mathematical model. Mathematical modelling has shown that synthesis in batch/repetitive batch reactor is the optimal pathway for production of this compound.

biocatalysis ; optically pure compound ; enzyme kinetics ; mathematical modelling

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