Palau'amine

Palau'amine is a toxic alkaloid compound synthesized naturally by Stylotella agminata, a species of sea sponge found in the southwest Pacific Ocean. The name of the molecule derives from the island nation of Palau, near which the sponges are found.

Palau'amine
Chemical structure of palau'amine
Names
Preferred IUPAC name
(3aR,4′R,5′S,10aS,11S,12S,13aS,13bR)-2,2′-Diamino-11-(aminomethyl)-12-chloro-5′-hydroxy-1,1′,3a,5′,10a,11,12,13a-octahydro-8H,10H-spiro[cyclopenta[3,4]pyrrolo[1,2-a]imidazo[4,5-b]pyrrolo[1,2-d]pyrazine-13,4′-imidazol]-8-one
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
MeSH C438976
UNII
  • InChI=1S/C17H22ClN9O2/c18-10-6(4-19)7-5-27-11(28)8-2-1-3-26(8)12-17(27,25-14(20)22-12)9(7)16(10)13(29)23-15(21)24-16/h1-3,6-7,9-10,12-13,29H,4-5,19H2,(H3,20,22,25)(H3,21,23,24)/t6-,7-,9+,10+,12+,13+,16+,17-/m1/s1
    Key: VYOQBYCIIJYKJA-VORKOXQSSA-N
  • Cl[C@@H]4[C@@]1(NC(=N/[C@H]1O)\N)[C@H]3[C@@]26/N=C(\N[C@H]6n5c(C(=O)N2C[C@@H]3[C@H]4CN)ccc5)N
Properties
C17H22ClN9O2
Molar mass 419.87 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

The substance was first isolated and described in 1993.[1] Containing nine nitrogen atoms, the molecule is considered highly complex. The precise atomic structure was pinned down in 2007,[2] and two years later the molecule was synthesized in the lab of Phil Baran at the Scripps Research Institute in La Jolla, California.[3][4] 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.[5]

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.[6]

Biological effects

Palau'amine is a proteasome inhibitor.[7]

References
  1. Kinnel, Robin B.; Gehrken, Henning Peter; Scheuer, Paul J. (1993). "Palau'amine: a cytotoxic and immunosuppressive hexacyclic bisguanidine antibiotic from the sponge Stylotella agminata". Journal of the American Chemical Society. 115 (8): 3376–3377. doi:10.1021/ja00061a065.
  2. Halford, Bethany (2007). "Sponge Alkaloids: Palau'amine Reconsidered". Chemical & Engineering News. 85 (10): 12. doi:10.1021/cen-v085n010.p012a.
  3. Seiple, Ian B.; Su, Shun; Young, Ian S.; Lewis, Chad A.; Yamaguchi, Junichiro; Baran, Phil S. (2010). "Total Synthesis of Palau'amine". Angewandte Chemie International Edition. 49 (6): 1095–8. doi:10.1002/anie.200907112. PMC 3367661. PMID 20041464.
  4. Madrigal, Alexis (2010-01-14). "Bizarre Sea Sponge Compound Finally Synthesized by Humans". Wired. Retrieved 2010-01-15.
  5. Usami, Yoshihide (2009-07-13). "Recent Synthetic Studies Leading to Structural Revisions of Marine Natural Products". Marine Drugs. 7 (3): 314–330. doi:10.3390/md7030314. ISSN 1660-3397. PMC 2763102. PMID 19841716.
  6. Ma Z, Lu J, Wang X, Chen C (Jan 7, 2011). "Revisiting the Kinnel–Scheuer hypothesis for the biosynthesis of palau'amine". Chem Commun. 47 (1): 427–9. doi:10.1039/c0cc02214d. PMC 2999656. PMID 20848010.
  7. 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 (2012). "Palau'amine and Related Oroidin-alkaloids Dibromophakellin and Dibromophakellstatin Inhibit the Human 20S Proteasome". Journal of Natural Products. 75 (5): 980–5. doi:10.1021/np300231f. PMC 3367325. PMID 22591513.
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