Synthesis of Nonnatural Helical Polypeptide via Asymmetric Polymerization and Reductive Cleavage of N-O Bond

Herein, we present a novel synthetic strategy, to amino-acid-free peptide synthesis based on postpolymerization conversion, for chiral nonnatural polypeptides. Optically active poly-N-alkoxyamides were prepared by our asymmetric polymerization as precursors of polypeptides, and the reductive cleavage of N-O bonds using a SmI2-THF complex was carried out. The reaction proceeded smoothly with quantitative conversion to afford a nonnatural polypeptide. The resulting polypeptide adopted a one-handed stable helical structure in solution, which was established by circular dichroism (CD) and theoretical calculations using density functional theory (DFT). The simulated spectra by time dependent (TD) DFT methods clearly indicated the validity of the proposed structure. The synthetic approach is a promising candidate for the synthesis of nonnatural polypeptides.