An aza-Diels–Alder route to quinoline-based unnatural amino acids and polypeptide surrogates

Abstract

Macromolecules composed of quinoline building blocks are viewed as valuable synthetic targets due to their potential as functional materials in optoelectronic devices and promise as therapeutic compounds for the treatment of disease. As such, a number of routes to polyquinolines, quinoline-decorated oligopeptides, and quinoline-containing oligoamides have been developed to date. Herein, by drawing inspiration from prior efforts, we synthesize quinoline-based unnatural amino acid building blocks via the aza-Diels–Alder (Povarov) reaction and then prepare polypeptide surrogates through iterative coupling of these building blocks on solid support. The described strategy uses economical procedures, requires straightforward conditions, and affords the targeted constructs in reasonable yields. Overall, our findings may expand the scope of possibilities for quinoline-based bioinspired polymers and facilitate the further development of quinoline-based functional materials.