Isolation and structural elucidation of the cytostatic linear depsipeptides dolastatin 13 and dehydrodolastatin 13

摘要

The Indian Ocean sea hare Dolabella auricularia has been found to contain a new cell growth inhibitory and antineoplastic (P388 leukemia) cyclodepsipeptide designated dolastatin 13 and a companion substance dehydrodolastatin 13. A series of high field (400 MHz) 2D-NMR experiments including sequential analyses by HMBC and NOE techniques and tandem mass spectrometry provided structural determinations. Dolastatin 13 and dehydrodolastatin 13 represent a new class of cyclodepsipeptides. Pharmaceutical preparations and therapeutic regimens employing these new cytostatic depsipeptides are disclosed. The depsipeptides have the following structure: CHEM o