Haligramides A and B, two new cytotoxic hexapeptides from the marine sponge Haliclona nigra

Bioassay-guided fractionation of a cytotoxic aqueous extract of the sponge Haliclona nigra provided two new cyclic hexapeptides, haligramides A (1) and B (2), in addition to the known peptide, waiakeamide (3). The structures of peptides 1 and 2 were elucidated by extensive NMR analyses and by comparison of their spectral data with those of waiakeamide (3). The identity of haligramide A (1) was confirmed by its oxidative conversion to waiakeamide (3). Further structural confirmation was provided by oxidation of peptides 1, 2, and 3 to the common bis-sulfone derivative 4.