Structural investigation of westiellamide analogues

The synthesis of westiellamide analogues, wherein the oxazoline units are replaced by oxazole or thiazole units, is presented. The structures of these analogues, and also of an imidazole-based analogue, were investigated using X-ray diffraction and DFT-based molecular modelling calculations. We could show that the oxazole-based peptide is almost planar, whereas the thiazole and the imidazole cyclic peptides have cone-like structures. Furthermore we could show that the flexibility of the systems essentially depends on the type of the azole building block. If oxazole-containing cyclopeptides are used, the scaffold takes an almost planar structure; bending the scaffold towards a cone-like structure, however, requires high energy. Imidazole-containing cyclopeptides show a complementary behaviour: while a planar structure can only be obtained with a high energetic input, a strong bending of the system is energetically favoured.

Graphical abstractThe structures and the flexibility of the westiellamide analogues 2–4 depend on the azole system. The aromatic units of 2 are almost coplanar, whereas in the case of 3 and 4 the azole moieties form cone-like structures.Figure optionsDownload full-size imageDownload as PowerPoint slide