Isolation and structural elucidation of the cytostatic linear depsipeptides dolastatin 13 and dehydrodolastatin 13
AssigneeArizona Board of Regents
InventorsGeorge R. Pettit, Yoshiaki Kamano
Life of this patent
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Abstract
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.sup.(1) and a companion substance dehydrodolastatin 13.sup.(2). 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: ##STR1##
Claims4
A cell growth inhibitory substance denominated dolastatin 13 having the structural formula:
- ##STR5## wherein:
- R.sub.1 =OH;
- R.sub.2 =H.
A cell growth inhibitory substance denominated dehydrodolastation 13 having the structural formula:
- ##STR6## wherein:
- R.sub.1 =R.sub.2 =.DELTA..sup.13,15.
A pharmaceutical preparation comprising a pharmaceutically acceptable carrier and an amount effective to inhibit cell growth of a natural or synthetic substance or a non-toxic pharmaceutically active derivative thereof, said substance having the structural formula:
- ##STR7## wherein:
- R.sub.1 =OH;
- R.sub.2 =H.
A pharamaceutical preparation comprising a pharmaceutically acceptable carrier and an amount effective to inhibit cell growth of a natural or synthetic substance or a non-toxic pharmaceutically active derivative thereof, said substance having the structural formula:
- ##STR8## wherein:
- R.sub.1 =R.sub.2 =.DELTA..sup.14,15.
Dependencies are inferred from the claim text.