Palau'amine is a toxic chlorinated

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

compound synthesized naturally by certain species of

sea sponge Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and are o ...

s. The name of the molecule derives from the

island nation An island country, island state, or island nation is a country whose primary territory consists of one or more islands or parts of islands. Approximately 25% of all independent countries are island countries. Island countries are historically ...

Palau Palau, officially the Republic of Palau, is an island country in the Micronesia subregion of Oceania in the western Pacific Ocean. The Republic of Palau consists of approximately 340 islands and is the western part of the Caroline Islands ...

, near where the first sponge species discovered to produce it, ''Stylotella agminata'', is found. It has since been isolated in other sponges, including '' Stylissa massa''. The substance was first isolated from ''Stylotella agminata'', a sponge found in the southwest

Pacific Ocean The Pacific Ocean is the largest and deepest of Earth's five Borders of the oceans, oceanic divisions. It extends from the Arctic Ocean in the north to the Southern Ocean, or, depending on the definition, to Antarctica in the south, and is ...

, and described in 1993. Containing nine

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atoms, the molecule is considered highly complex. The precise atomic structure was pinned down in 2007, and two years later, the molecule was synthesized in the lab of

Phil Baran Phil S. Baran (born August 10, 1977) is a synthetic organic chemist and Professor in the Department of Chemistry at the Scripps Research Institute.Scripps Research Institute Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...

La Jolla, California La Jolla ( , ) is a hilly, seaside neighborhood in San Diego, California, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781. The climate is mild, with an average daily temperature o ...

. Early efforts towards its synthesis were directed at a misassigned structure featuring a ''cis-'' rather than ''trans-''5/5 ring fusion, an error that was made because the ''trans''-5/5 ring system is some 6 kcal/mol less stable than the ''cis''-configured system.

Biomimetic synthesis

Based on the hypothesized biosynthesis of palau'amine, a proposed pathway to this dimeric

pyrrole Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula . It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-methylpyrrol ...

- imidazole alkaloid includes a key oxidation of a β- ketoester with manganese(III) acetate to initiate a cascade radical cyclization, producing an

ageliferin Ageliferin is a chemical compound produced by some sponges. It was first isolated from Caribbean and then Okinawan marine sponges in the genus ''Agelas''. It often co-exists with the related compound sceptrin and other similar compounds. It has ...

skeleton.

Biological effects

Palau'amine is a

proteasome inhibitor Proteasome inhibitors (INN stem ) are drugs that block the action of proteasomes. Proteasomes are large proteins complexes that are used to break down other proteins. These inhibitors are being studied for the treatment of cancer. Drugs such as ...

.{{cite journal, title=Palau'amine and Related Oroidin-alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome, journal=Journal of Natural Products, volume=75, issue=5, pages=980–5, doi=10.1021/np300231f, pmid=22591513, pmc=3367325, year=2012, last1=Lansdell, first1=T. A, last2=Hewlett, first2=N. M, last3=Skoumbourdis, first3=A. P, last4=Fodor, first4=M. D, last5=Seiple, first5=I. B, last6=Su, first6=S, last7=Baran, first7=P. S, last8=Feldman, first8=K. S, last9=Tepe, first9=J. J

References

Alkaloids Organochlorides Halogen-containing alkaloids Guanidine alkaloids Amines Spiro compounds Nitrogen heterocycles Proteasome inhibitors