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

Abstract We designed a deoxazoline-ascidiacyclamide ( d ASC), cyclo(– l –Ile– l – allo –Thr– d –Val–thiazole–) 2 , diastereomer having 10 S , 11 R , 37 R , and 38 S configurations ([ SR,RS ] d ASC) and a corresponding product having 10 S , 11 S , 37 R , and 38 R 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 ] d ASC is folded in a manner similar to other d ASC 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.