Pseudopeptide Foldamers: The Homo-Oligomers of Pyroglutamic Acid

摘要

As a part of a program evaluating substituted #gamma#-lactams as conformationally constrained building blocks of pseudopeptide foldamers, we synthesized the homo-oligomers of L-pyroglutamic acid up to the tetramer level by solution methods. The preferred conformation of this pseudopeptide series in structure-supporting solvents was assessed by FT-IR absorption, ~1H NMR and CD techniques. In addition, the crystal structure of the N~#alpha#-protected dimer was established by X-ray diffraction. A high-level DFT computational modeling was performed based on the crystallographic parameters. In this analysis, we demonstrated that an #alpha#C-H…O=C intramolecular hydrogen bond is responsible for the stabilization of the s-trans L-pGlu-L-pGlu conformation by 1.4 kcal mol~(-1). This effect can be easily detected by ~1H NMR spectroscopy, owing to the anomalous chemical shifts of the #alpha#CH protons present in all of the oligomers. In summary, we have developed a new polyimide-based, foldameric structure that, if appropriately functionalized, has promise as a rigid scaffold for novel functions and applications.