engleski

Halohydrin dehalogenase-catalysed synthesis of fluorinated aromatic chiral building blocks

Halohydrin dehalogenases (HHDHs) catalyse enantioselective formation and conversion of epoxides. They can be applied in the kinetic resolution of racemic epoxides by utilising a range of anionic nucleophiles such as azide, cyanide, cyanate or nitrite.[1, 2] The ring- opening products and remaining epoxides are versatile and important synthetic intermediates for fine chemicals. In this work HHDH was employed for the transformation of epoxides bearing fluoroaryl groups (Figure 1). Fluoroaromatic compounds are widely used as starting materials for chemical syntheses, especially pharmaceuticals and agrochemicals. Introduction of fluorine atoms into the molecule usually increases target effectiveness, biological half-life, bioabsorption etc. The growing interest in fluorinated organics makes the development of synthetic procedures leading to such compounds desirable. Kinetic resolution of a series of fluorinated styrene oxide derivatives was studied using the enzyme from Agrobacterium radiobacter AD1 (HheC) and a variant W249P.[3] A mutant HheC-W249P catalysed nucleophilic ring-opening with azide and cyanide ions with excellent enantioselectivity (Evalues up to >200) and higher activity compared to the wild- type, which gives access to various enantiopure β- substituted alcohols and epoxides. It was found that the enzyme tolerates substrates in concentrations over 50 mM. However, different side reactions were observed at elevated concentrations and with prolonged reaction time. The biocatalytic azidolysis and cyanolysis of racemic 4-CF3-styrene oxide were performed on preparative scale, affording (R)-2-azido-1-(4-trifluoromethylphenyl)- ethanol in 38% yield and 97% ee, and (S)-3- hydroxy-3-(4-trifluoromethylphenyl)-propionitrile in 30% yield and 98% ee.

biocatalysis ; halohydrin dehalogenase ; epoxide ; kinetic resolution

nije evidentirano