SEMINAR: Bayliss Seminar Series

Marine invertebrate-derived polycyclic alkaloids with 16-18π electron containing cores have therapeutic interest since they interfere with many biological disease targets. These compounds, which are commonly isolated from sponges and tunicates, are an important class of biologically active natural products. In particular those having tryptophan and dopamine building blocks, often interact with many disease targets. The marine environment contains over 80% of the world’s plant and animal species, and in recent years, many bioactive compounds have been isolated from this source. Marine organisms like sponges, tunicates, soft corals, sea hares, nudibranchs, bryozoans, and sea slugs have yielded thousands of metabolites, many of which have promising biological properties.

In 2002, upon a reinvestigation of the Indo-Pacific marine sponge Xestospongia carbonaria, alpkinidine was isolated. Alpkinidine is one of the few pentacyclic, bisannulated pyrroloacridines isolated from nature, making them rare compared to their counterparts, the pyridoacridines of which more than forty are known. Structurally, pyridoacridines have a six membered D-ring fused to an ABC acridine core, whereas pyrroloacridines have a contracted D-ring. There has been very little published on the biological activity of alpkinidine but as part of the original isolation, Crew and co-workers demonstrated that Alpkinidine is selectively toxic to murine leukemia cells over colon adenocarcinoma cells. This coupled with the novel structure of this compound makes it an appealing target for synthesis.