The highly polarised C-F bond can participate in a variety of stereoelectronic interactions with adjacent functional groups, and these interactions can favour certain molecular conformations over others. Thus, it is possible to rationally �program� molecules to adopt desired conformations by decorating them with carefully-designed patterns of fluorine substituents. This presentation will describe the synthesis of a novel collection of fluorinated amino acids: specifically, the various stereoisomers of 2,3-difluoro-4-aminobutyric acid (2,3-difluoro-GABA). These molecules have been thoroughly characterised by NMR, X-ray crystallography and molecular modelling, and it emerges that the different stereoisomers have very different preferred conformations. The syn-isomers prefer an extended zigzag shape, whereas the anti-isomers exhibit conformational disorder and a bent carbon chain. Current work is focused on incorporating these shape-controlled building blocks into a variety of peptide systems (eg. antimicrobial natural products; RGD peptides; and GABA receptor ligands) that crucially rely on 3D conformation for optimal biological activity.

Fluorinated amino acids: Building blocks for the synthesis of   shape-controlled bioactive peptides

243rd National Meeting (2012)

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