A spirocyclic backbone accesses new conformational space in an extended, dipole-stabilized foldamer.

Most aromatic foldamers adopt uniform secondary structures, offering limited potential for the exploration of conformational space and the formation of tertiary structures. Here we report the incorporation of spiro bis-lactams to allow controlled rotation of the backbone of an iteratively synthesised foldamer. This enables precise control of foldamer shape along two orthogonal directions, likened to the aeronautical yaw and roll axes.

Chiral, sequence-definable foldamer-derived macrocycles.

Nature's oligomeric macromolecules have been a long-standing source of inspiration for chemists producing foldamers. Natural systems are frequently conformationally stabilised by macrocyclisation, yet this approach has been rarely adopted in the field of foldamer chemistry. Here we present a new class of chiral cyclic trimers and tetramers formed by macrocyclisation of open-chain foldamer precursors.