From Inactive Nortopsentin D, a Novel Bis(indole) Alkaloid Isolated from the Axinellid Sponge Dragmacidon sp. from Deep Waters South of New Caledonia, to a Strongly Cytotoxic Derivative

Nortopsentin D ( 5 ), a bis(indole) alkaloid unique for bearing a 2‐amino‐methylimidazole appendage at the central 1 H ‐imidazol‐5(4 H )‐one nucleus, was isolated in abundance, besides the putative biogenetic precursor 6 of its appendage, from the deep‐water axinellid sponge Dragmacidon sp. Structural elucidation of 5 by NMR and MS methods heavily relied on its N ‐methyl derivatives 8–11 . Unusually for topsentin‐type structures, natural 5 and semisynthetic methyl derivatives 8 and 10 proved inactive on KB tumoural cells, while introduction of the last three methyl groups, amazingly led to highly cytotoxic 11 .