Haloalkane dehalogenase catalysed desymmetrisation and tandem kinetic resolution for the preparation of chiral haloalcohols

• Published in: Tetrahedron Vol. 68; no. 37; pp. 7645 - 7650
• Main Authors: Westerbeek, Alja, van Leeuwen, Jan G.E., Szymański, Wiktor, Feringa, Ben L., Janssen, Dick B.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.09.2012; Elsevier
• Subjects: Bacteria; Biocatalysis; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Cascade chemical reactions; Conversion; Desymmetrisation; Enantioselective; Escherichia coli; Fundamental and applied biological sciences. Psychology; Haloalcohols; Haloalkane dehalogenase; Kinetic resolution; Mathematical analysis; Methods. Procedures. Technologies; Reaction kinetics; Tetrahedrons; Desymmetrisation; Haloalkane dehalogenase; Biocatalysis; Enantioselective; Kinetic resolution; Haloalcohols; Catalytic reaction; Enantioselectivity; Haloalcohol; Enzyme; Escherichia coli; Desymmetrization; Chiral compound; Tandem reaction; Optical resolution; Bacteria; Hydrolases; Enantiomeric excess; Optical purity; Bromine Organic compounds; Chemical synthesis; Enterobacteriaceae
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.06.059

Six different bacterial haloalkane dehalogenases were recombinantly produced in Escherichia coli, purified, and used to catalyse the conversion of prochiral short-chain dihaloalkanes and a meso dihaloalkane, yielding enantioenriched haloalcohols. A two-reaction one-enzyme process was established in which the desymmetrisation of a dihaloalkane is followed by kinetic resolution of the chiral haloalcohol that is produced in the first step. In case of 1,3-dibromo-2-methylpropane and 1,3-dibromo-2-phenylpropane, an increase of the enantiomeric excess of the respective haloalcohol was observed in time, leading to ee values of >97%, with analytical yields of 24 and 52%, respectively. The results show that haloalkane dehalogenases can be used for the production of highly enantioenriched haloalcohols and that in some cases product enantiopurity can be improved by allowing a two-step one-enzyme tandem reaction. [Display omitted]