β-Pseudopeptide foldamers. The homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D–Oxac)

Abstract

A total synthesis in solution and a conformational analysis of the homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D–Oxac) to the tetramer level are described. As the D–Oxac building block contains both an oxazolidin-2-one and a β-amino acid group, it may represent a new type of conformationally constrained tool for the construction of β-pseudopeptide foldamers. A conformational investigation using NMR and an extensive, unconstrained analysis with a Monte Carlo search to the octamer level, both in water and in chloroform, showed that these homo-oligomers tend to fold in a regular helical structure in a competitive solvent, such as water. Since aqueous solutions are of major relevance for biological systems, these molecules are good candidates for application to these environments.