Oligo(β-peptoid)s with Backbone Chirality from Aspartic Acid Derivatives: Synthesis and Property Investigation

Poly(β-peptoid)s (N-substituted poly-β-alanines) are an intriguing class of pseudopeptidic materials for biomedical applications, but the polymers prepared by solution polymerization have restricted diversity and functionality due to synthetic difficulty. Synthesis of structurally diverse poly(β-peptoid)s is highly desirable yet challenging. Herein, we report a new approach to synthesize skeletal chiral β-peptoid polymers from readily available aspartic acid derivatives. Two types of N-substituted β³-homoalanine monomers, i.e., N-(methyl propionate)-Asp-OMe ( MeP-Asp-OMe) and N-(tert-butyl propionate)-Asp-OMe ( tBuP-Asp-OMe), were synthesized in high yield via an aza-Michael addition reaction between l-aspartic acid-1-methyl ester (l-Asp-OMe) and acrylate species. Both N-substituted β³-homoalanines can be readily converted into polymerizable N-substituted β³-homoalanine N-carboxyanhydrides (β-NNCAs). Subsequent ring-opening polymerization (ROP) of these β-NNCA monomers provides access to oligo(β-peptoid)s and mPEG-poly(β-peptoid) diblocks with backbone chirality. Their conformations were preliminarily studied by circular dichroism (CD) spectra and Fourier transform infrared spectroscopy (FT-IR). The synthetic strategy would significantly facilitate the development of novel poly(β-peptoid)s with well-defined and diverse structures.