Enzymatic dynamic kinetic resolution of epihalohydrins

The haloalcohol dehalogenase from Agrobacterium radiobacter AD1 catalyses the reversible ring closure of vicinal haloalcohols to produce epoxides and halides. In the ring opening of epoxides, nonhalide nucleophiles such as N3− are accepted. The enantioselective irreversible ring opening of an epihalohydrin by N3−, combined with racemisation caused by a reversible ring opening by a halide, resulted in an enzymatic dynamic kinetic resolution yielding optically active (S)-1-azido-3-halo-2-propanol. With epichlorohydrin as a substrate, the rate of ring opening by N3− was higher than the rate of racemisation, resulting in a mixed kinetic resolution and dynamic kinetic resolution. With epibromohydrin as the substrate, the racemisation rate was higher than the rate of ring opening, resulting in an efficient dynamic kinetic resolution. By optimising the pH of the medium and the concentrations of N3− and Br−, the product (S)-1-azido-3-bromo-2-propanol could be obtained in 84% yield and 94% ee. An (R)-enantiomer selective ring closure of this bromoalcohol, catalysed by the same enzyme, caused a simultaneously occurring kinetic resolution, yielding when the conversion progressed, an increase in enantiopurity of (S)-1-azido-3-bromo-2-propanol to >99% ee with a yield of 77%. This compound and the ring-closed product glycidyl azide can be used as chiral synthetic building blocks. [Copyright &y& Elsevier]