Triproamide and Pemukainalides, Cyclic Depsipeptides from the Marine Cyanobacterium Symploca hydnoides .

A new cyclic depsipeptide, triproamide ( 1 ), containing the rare 4-phenylvaline (dolaphenvaline, Dpv) and a β-amino acid, dolamethylleucine (Dml), originally found in dolastatin 16, was isolated from the polar VLC-derived fraction of the extracts prepared from the marine cyanobacterium Symploca hydnoides . Triproamide ( 1 ) was isolated along with the known molecule kulokainalide-1 ( 2 ), as well as its two new analogues, pemukainalides A ( 3 ) and B ( 4 ). Their planar structures were elucidated based on extensive NMR and mass spectrometric data. The absolute and relative configurations of the compounds were determined utilizing a combination of Marfey's method, J- based configuration, and chiral-phase HPLC analyses. Kulokainalide-1 ( 2 ) and pemukainalide A ( 3 ) exhibited cytotoxicity against the MOLT-4 leukemia cell line with IC 50 values of 5.9 and 5.6 μM, respectively.