Palau'amine is a toxic alkaloid compound synthesized naturally by certain species of sea sponges. The name of the molecule derives from the

island nation An island country, island state or an 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 ...

of Palau, 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 ''Stylissa'' is a genus of sponges in the family Scopalinidae. Species * ''Stylissa acanthelloides'' Lévi, 1961 * '' Stylissa caribica'' Lehnert & van Soest, 1998 * ''Stylissa carteri'' Dendy, 1889 * ''Stylissa constricta'' Pulitzer-Finali, 198 ...

''. The substance was first isolated from ''Stylotella agminata'', a sponge found in the southwest Pacific Ocean, and described in 1993. Containing nine nitrogen 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 at the Scripps Research Institute in

La Jolla, California La Jolla ( , ) is a hilly, seaside neighborhood within the city of San Diego, California, United States, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781. La Jolla is surrounded on ...

. 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 C4 H4 NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-meth ...

- imidazole alkaloid includes a key oxidation of a β-

ketoester In organic chemistry, keto acids or ketoacids (also called oxo acids or oxoacids) are organic compounds that contain a carboxylic acid group () and a ketone group ().Franz Dietrich Klingler, Wolfgang Ebertz "Oxocarboxylic Acids" in Ullmann's En ...

with

manganese(III) acetate Manganese(III) acetate describes a family of materials with the approximate formula Mn(O2CCH3)3. These materials are brown solids that are soluble in acetic acid and water. They are used in organic synthesis as oxidizing agents. Structure Altho ...

to initiate a cascade

radical cyclization Radical cyclization reactions are organic chemical transformations that yield cyclic products through radical intermediates. They usually proceed in three basic steps: selective radical generation, radical cyclization, and conversion of the cyclize ...

, producing an ageliferin skeleton.

Biological effects

Palau'amine is a proteasome inhibitor.{{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