The design, synthesis, and conformational
analysis of an oligobenzanilide helix mimetic scaffold capable
of simultaneous mimicry of two faces of an α-helix is reported.
The synthetic methodology provides access to diverse
monomer building blocks amenable to solid-phase assembly
in just four synthetic steps. The conformational flexibility of
model dimers was investigated using a combination of solid
and solution state methodologies supplemented with DFT
calculations. The lack of noncovalent constraints allows for
significant conformational plasticity in the scaffold, thus
permitting it to successfully mimic residues i, i+2, i+4, i+6, i
+7, and i+9 of a canonical α-helix.