title: Aldolase-catalysed stereoselective synthesis of fluorinated small molecules.
abstract: The introduction of fluorine has been widely exploited to tune the biological functions of small molecules. Indeed, around 20% of leading drugs contain at least one fluorine atom. Yet, despite profound effects of fluorination on conformation, there is only a limited toolkit of reactions that enable stereoselective synthesis of fluorinated compounds. Aldolases are useful catalysts for the stereoselective synthesis of bioactive small molecules; however, despite fluoropyruvate being a viable nucleophile for some aldolases, the potential of aldolases to control the formation of fluorine-bearing stereocentres has largely been untapped. Very recently, it has been shown that aldolase-catalysed stereoselective carboncarbon bond formation with fluoropyruvate as nucleophile enable the synthesis of many α-fluoro β-hydroxy carboxyl derivatives. Furthermore, an understanding of the structural basis for the stereocontrol observed in these reactions is beginning to emerge. Here, we review the application of aldolase catalysis in the stereocontrolled synthesis of chiral fluorinated small molecules, and highlight likely areas for future developments.
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK; School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Windle
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK; School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address: a.berry@leeds.ac.uk.
authors.forename: Alan
authors.initials: A
authors.lastname: Berry
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK; School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. Electronic address: a.s.nelson@leeds.ac.uk.
authors.forename: Adam
authors.initials: A
authors.lastname: Nelson
mesh_terms: D055162:Biocatalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D005461:Fluorine / Q000737:chemistry*; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D054852:Small Molecule Libraries; D005461:Fluorine; D005634:Fructose-Bisphosphate Aldolase