Synthesis and conformation of fluorinated beta-peptidic compounds

Experimental and theoretical data indicate that, for alpha-fluoroamides, the FCC(O)N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal CF and CN(CO) bonds in N-beta-fluoroethylamides. This study details the synthesis of a series of fluorinated beta-peptides (1-8) designed to use these stereoelectronic effects to control the conformation of beta-peptide bonds. X-ray crystal structures of these compounds revealed the expected conformations: with fluorine beta to a nitrogen adopting a gauche conformation, and fluorine alpha to a CO group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a beta-peptide bond, with the possibility of directing the secondary structures of beta-peptides.