The synthesis and conformational analysis of a novel class of foldamers containing (S)‐β3‐homophenylglycine [(S)‐β3‐hPhg] and D‐4‐carboxy‐oxazolidin‐2‐one (D‐Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1H NMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11‐membered hydrogen‐bonded rings as the preferred secondary structure type. The few formal helix alternatives can be excluded in particular by steric effects of the oxazolidin‐2‐one rings. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Six cyclic pseudopeptides with the general formula cyclo-(L-AA-D-Oxd) n [where AA is an α-amino acid, D-Oxd is trans-(4R,5S)-4-carboxy-5-methyloxazolidin-2-one and n = 3, 4] have been designed and efficiently synthesized in the liquid phase in good overall yields. The crucial step is the macrocyclization, which always occurs in satisfactory yields regardless of the cycle dimension and the nature of various func-