Synthesis and Conformation of Fluorinated β-Peptidic Compounds

Experimental and theoretical data indicate that, for α‐fluoroamides, the FCC(O)N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal CF and CN(CO) bonds in N‐β‐fluoroethylamides. This study details the synthesis of a series of fluorinated β‐peptides (1–8) designed to use these stereoelectronic effects to control the conformation of β‐peptide bonds. X‐ray crystal structures of these compounds revealed the expected conformations: with fluorine β to a nitrogen adopting a gauche conformation, and fluorine α to a CO group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a β‐peptide bond, with the possibility of directing the secondary structures of β‐peptides. Making moves: X‐ray crystal structures were obtained for a series of α‐fluoro‐β‐amino acids and small fluorinated β‐peptides (see picture for an example). When fluorine was positioned α to a carbonyl group, the FCCO moiety was found to adopt an antiperiplanar conformation; but when fluorine was positioned β to an amide nitrogen, a conformation in which CF and CN(CO) bonds are gauche was favoured.