Semisynthesis of S-Desoxybrevetoxin-B2 and Brevetoxin-B2, and Assessment of Their Acute Toxicities

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• 作者：Andrew I. Selwood ; Roel van Ginkel ; Alistair L. Wilkins ; Rex Munday ; John S. Ramsdell ; Dwayne J. Jensen ; Janine M. Cooney ; and Christopher O. Miles
• 刊名：Chemical Research in Toxicology
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：21
• 期：4
• 页码：944-950
• 全文大小：173k
• 年卷期：v.21,no.4(April 2008)
• ISSN：1520-5010

文摘

Brevetoxins are neurotoxins associated with blooms of marine algae such as Karenia brevis and can accumulate in the marine food chain, causing intoxication of marine animals and people consuming seafood. Brevetoxin-B2 (5) is a toxic metabolite produced in shellfish exposed to algae that contain brevetoxin-B (1). S-Desoxybrevetoxin-B2 (4) has been proposed as a cometabolite produced during this transformation, and while LC-MS analyses suggest its presence in shellfish, it has not yet been isolated and characterized. Studies on these materials are severely constrained by the difficulty of obtaining and purifying them from natural sources. We have developed a convenient one-pot conversion of commercially available brevetoxin-B (1) into S-desoxybrevetoxin-B2 (4), and a simple method for converting 4 into brevetoxin-B2 (5). Full NMR and mass-spectral characterization of 4 and 5 confirmed their structures and showed that the ratio of diastereoisomers in the synthetic 4 and 5 was similar to that observed in naturally contaminated shellfish. The LD₅₀ values for 4, 5, and dihydrobrevetoxin-B (6) by ip injection in mice were 211, 400, and 250 µg/kg, respectively. The methodology for synthesis of brevetoxin metabolites should greatly facilitate toxicological, biochemical and immunochemical studies of these substances, as well as the production of analytical standards.