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

Abstract

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.