Palau'amine Explained

Palau'amine is a toxic chlorinated alkaloid compound synthesized naturally by certain species of sea sponges. The name of the molecule derives from the island nation 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.^[1]

The substance was first isolated from Stylotella agminata, a sponge found in the southwest Pacific Ocean, and described in 1993.^[2] Containing nine nitrogen atoms, the molecule is considered highly complex. The precise atomic structure was pinned down in 2007,^[3] and two years later, the molecule was synthesized in the lab of Phil Baran at the Scripps Research Institute in La Jolla, California.^{[4] [5]} 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.^[6]

Biomimetic synthesis

Based on the hypothesized biosynthesis of palau'amine, a proposed pathway to this dimeric pyrrole-imidazole alkaloid includes a key oxidation of a β-ketoester with manganese(III) acetate to initiate a cascade radical cyclization, producing an ageliferin skeleton.^[7]

Biological effects

Palau'amine is a proteasome inhibitor.^[8]

References

1. Rohde S, Gochfeld DJ, Ankisetty S, Avula B, Schupp PJ, Slattery M . Spatial variability in secondary metabolites of the indo-pacific sponge Stylissa massa . . 38 . 5 . 463–75 . May 2012 . 22569832 . 10.1007/s10886-012-0124-8.
2. Palau'amine: a cytotoxic and immunosuppressive hexacyclic bisguanidine antibiotic from the sponge Stylotella agminata . Robin B. . Kinnel. Henning Peter . Gehrken . Paul J. . Scheuer . Journal of the American Chemical Society . 1993 . 115 . 8 . 3376–3377 . 10.1021/ja00061a065.
3. Chemical & Engineering News. 2007 . 85 . 10 . 12. Sponge Alkaloids: Palau'amine Reconsidered . Bethany . Halford . 10.1021/cen-v085n010.p012a.
4. 10.1002/anie.200907112 . 20041464 . Angewandte Chemie International Edition . Total Synthesis of Palau'amine. Ian B. . Seiple . Shun . Su . Ian S. . 49 . 6 . Young . Chad A. . Lewis . Junichiro . 1095–8 . Yamaguchi . Phil S.. Baran . Phil S. Baran . 2010. 3367661 .
5. Alexis . Madrigal . 2010-01-14 . Bizarre Sea Sponge Compound Finally Synthesized by Humans . Wired . 2010-01-15.
6. Usami. Yoshihide. 2009-07-13. Recent Synthetic Studies Leading to Structural Revisions of Marine Natural Products. Marine Drugs. 7. 3. 314–330. 10.3390/md7030314. 1660-3397. 2763102. 19841716. free.
7. Chem Commun. Jan 7, 2011. 47. 1. 427–9. Revisiting the Kinnel–Scheuer hypothesis for the biosynthesis of palau'amine . Ma Z, Lu J, Wang X, Chen C . 20848010. 10.1039/c0cc02214d. 2999656.
8. Palau'amine and Related Oroidin-alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome. Journal of Natural Products. 75. 5. 980–5. 10.1021/np300231f. 22591513. 3367325. 2012. Lansdell. T. A. Hewlett. N. M. Skoumbourdis. A. P. Fodor. M. D. Seiple. I. B. Su. S. Baran. P. S. Feldman. K. S. Tepe. J. J.