Cyclic α,β-peptoid octamers with differing side chain patterns: synthesis and conformational investigation

The solution-phase synthesis and cyclisation of three alpha,beta-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids. The X-ray crystal structure of cyclic octamer C, the first high-resolution structure for the alpha,beta-peptoid backbone, was also obtained from methanol. Combined solid- and solution-phase studies allowed the identification of the N-2-(benzyloxy)ethyl side chain on the beta-residue of the heterogeneous backbone as a key structural feature driving the increased conformational stability for octamer C.