AbstractThe syntheses of a C4‐ and a C2‐symmetric scaffold are presented. The first is composed of four imidazole units, while the second contains two imidazole and two oxazole moieties. The synthesis of the key building block for both systems has been fundamentally improved. Starting from these scaffolds, various platforms possessing two or four arms can easily be prepared. The structures of the scaffolds, together with that of a C4‐symmetric oxazole scaffold, were investigated in the solid state and in the gas phase. We found that these 24‐membered cyclic peptides exist as two different structure types. In one case (type I), the nitrogen atoms of the azole units pointing into the interior of the macrocycle form a square, whereas in the second case (type II), they form a parallelogram. The type of molecular structure does not depend on the symmetry of the system, but on the type of azole used. Cyclic systems composed of four imidazole units are present in the type I structure, whereas systems consisting of four oxazole units exhibit the type II nature. Structure type II is also present in cycles composed of two oxazole units and two imidazole units. The existence of the different structure types can be explained in terms of the different orbital energies of the imidazole and oxazole systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)