Semisynthesis of S-desoxybrevetoxin-B2 and brevetoxin-B2, and assessment of their acute toxicities.
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 LD 50 values for 4, 5, and dihydrobrevetoxin-B ( 6) by ip injection in mice were 211, 400, and 250 microg/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.
Selwood
Andrew I
AI
Cawthron Institute, Private Bag 2, Nelson, New Zealand.
Ginkel
Roel van
Rv
Wilkins
Alistair L
AL
Munday
Rex
R
Ramsdell
John S
JS
Jensen
Dwayne J
DJ
Cooney
Janine M
JM
Miles
Christopher O
CO
D000818:Animals; D005260:Female; D007928:Lethal Dose 50; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D035964:Oxocins / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000095702:Polyether Toxins
D008387:Marine Toxins; D035964:Oxocins; D013438:Sulfhydryl Compounds; C530719:S-desoxybrevetoxin-B2; D000095702:Polyether Toxins; C530720:brevetoxin-B2; C053342:brevetoxin