Isolation of dolastatin 10 from the marine cyanobacterium Symploca speciesVP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1

The potent antitumor agent dolastatin 10 (1) was originally isolated from t he sea hare Dolabella auricularia, and we now report its isolation from the marine cyanobacterium Symploca sp. VP642 from Palau. The chemically relate d analogue symplostatin 1 (2) has been reisolated from Guamanian and Hawaii an varieties of S. hydnoides and its total stereochemistry completed by det ermining the N,N-dimethylisoleucine unit to be L. Symplostatin 1 (2), like dolastatin 10 (1), is a potent microtubule inhibitor. The antitumor activit y of 2 was assessed in vivo against several murine tumors. Symplostatin 1 ( 2) was effective against a drug-insensitive mammary tumor and a drug-insens itive colon tumor; however, it was only slightly effective against two MDR tumors.