Fluorinated Aromatic Monomers as Building Blocks To Control α‑Peptoid Conformation and Structure

Peptoids are peptidomimetics
of interest in the fields of drug
development and biomaterials. However, obtaining stable secondary
structures is challenging, and designing these requires effective
control of the peptoid tertiary amide cis/trans equilibrium.
Herein, we report new fluorine-containing aromatic monomers that can
control peptoid conformation. Specifically, we demonstrate that a
fluoro-pyridine group can be used to circumvent the need for monomer
chirality to control the cis/trans equilibrium. We
also show that incorporation of a trifluoro-methyl group (NCF3Rpe) rather than a methyl group
(NRpe) at the α-carbon of a monomer gives rise
to a 5-fold increase in cis-isomer preference.