A flat squared conformation of an ascidiacyclamide derivative caused by chiral modification of an oxazoline residue.

We designed a deoxazoline-ascidiacyclamide (dASC), cyclo(-L-Ile-L-allo-Thr-D-Val-thiazole-)(2), diastereomer having 10S, 11R, 37R, and 38S configurations ([SR,RS]dASC) and a corresponding product having 10S, 11S, 37R, and 38R configurations ([SS,RR]ASC) with the aim of understanding better the relationship between conformational behaviour and chirality. X-ray diffraction analysis revealed that [SR,RS]dASC is folded in a manner similar to other dASC analogues. By contrast, [SS,RR]ASC is a novel, flat conformer that is larger than the major square and folded ASC conformers and contains a cavity created by the flat peptide ring. In addition, [SS,RR]ASC retains approximately 60% of the cytotoxicity of the parent molecule.