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Brevetoxin (PbTx), or brevetoxins, are a suite of cyclic polyether compounds produced naturally by a species of dinoflagellate known as Karenia brevis. Brevetoxins are neurotoxins that bind to voltage-gated sodium channels in nerve cells, leading to disruption of normal neurological processes and causing the illness clinically described as neurotoxic shellfish poisoning (NSP).
Although brevetoxins are most well-studied in K. brevis, they are also found in other species of Karenia and at least one large fish kill has been traced to brevetoxins in Chattonella.
- Brevetoxin-1 (PbTx-1) R = -CH2C(=CH2)CHO
- Brevetoxin-7 (PbTx-7) R = -CH2C(=CH2)CH2OH
- Brevetoxin-10 (PbTx-10) R = -CH2CH(-CH3)CH2OH
- Brevetoxin-2 (PbTx-2) R = -CH2C(=CH2)CHO
- Brevetoxin-3 (PbTx-3) R = -CH2C(=CH2)CH2OH
- Brevetoxin-8 (PbTx-8) R = -CH2COCH2Cl
- Brevetoxin-9 (PbTx-9) R = -CH2CH(CH3)CH2OH
- Brevetoxin-5 (PbTx-5): like PbTx-3, but acetylated hydroxyl group in position 38.
- Brevetoxin-6 (PbTx-6): like PbTx-2, but double bond 27-28 is epoxidated.
Brevetoxin-B was synthesized in 1995 by K. C. Nicolaou and coworkers in 123 steps with 91% average yield (final yield ~9·10−6). and in 2004 a total of 90 steps with an average 93% yield for each step (0.14% overall).
K. C. Nicolaou and coworkers reported their synthesis of Brevetoxin-1 in 1998. In 2009, Michael Crimmins and co-workers reported their synthesis of Brevetoxin-1 as well.
A proposed biosynthetic route includes a novel polyketide formation involving Claisen condensation of a dicarboxylic acid with the alpha-position of the second carboxylic function with a loss of a carboxyl group.
- ^ a b Watkins SM, Reich A, Fleming LE, Hammond R (2008). "Neurotoxic Shellfish Poisoning". Marine Drugs 6 (3): 431–455. doi:10.3390/md20080021. PMC 2579735. PMID 19005578.
- ^ Nicolaou KC, Yang Z, Shi G, Gunzner JL, Agrios KA, Gärtner P (1998). "Total Synthesis of Brevetoxin A". Nature 392 (6673): 264–269. doi:10.1038/32623. PMID 9521320.
- ^ a b Matsuo G, Kawamura K, Hori N, Matsukura H, Nakata T (2004). "Total Synthesis of Brevetoxin-B" (pdf). Journal of the American Chemical Society 126 (44): 14374–14376. doi:10.1021/ja0449269.
- ^ Nicolaou KC, Rutjes FP, Theodorakis EA, Tiebes J, Sato M, Untersteller E (1995). "Total Synthesis of Brevetoxin B. 3. Final Strategy and Completion". Journal of the American Chemical Society 117 (41): 10252–10263. doi:10.1021/ja00146a010.
- ^ Nicolaou KC, Yang Z, Shi GQ, Gunzner JL, Agrios KA, Gärtner P (1998). "Total Synthesis of Brevetoxin A". Nature 392 (6673): 264–269. doi:10.1038/32623. PMID 9521320.
- ^ Crimmins MT, Zuccarello JL, Ellis JM, McDougall PJ, Haile PA, Parrish JD, Emmitte KA (2009). "Total Synthesis of Brevetoxin A". Organic Letters 11 (2): 489–492. doi:10.1021/ol802710u.
- ^ Chou HN, Shimizu Y (1987). "Biosynthesis of Brevetoxins. Evidence for the Mixed Origin of the Backbone Carbon Chain and the Possible Involvement of Dicarboxylic Acids". Journal of the American Chemical Society 109 (7): 2184–2185. doi:10.1021/ja00241a048.
See also