Non-natural 3-Arylmorpholino-β-amino Acid as a PPII Helix Inducer

Abstract

A new non-natural β-amino acid, named 3-Ar-β-Morph, was designed and synthesized via a regio- and diastereoselective Pd-catalyzed C(sp3)H-arylation of the corresponding 2S,6S-(6-methoxymorpholin-2-yl)carboxylic acid, readily available from glucose. According to the computational prevision and confirmed by IR and NMR data, the insertion of 3-Ar-β-Morph in a model foldamer represents a way to stabilize a PPII-like helix through the presence of two γ-turns, secondary structure motifs induced by the morpholine ring, and the trans-tertiary amide bond.