Structure of Brevetoxin A as Constructed from NMR and MS Data

Brevetoxins (BTX) exemplified by BTX-B C₅OH70₀14(1) are neurotoxins produced by Gymnodinium breve. The blooms of these dinoflagellates known as red tide have led to massive fish kills, mollusk poisoning, etc. along the Florida coast and the Gulf of Mexico. Up to date, a total of five BTX's with the same skeleton have been found. The skeleton is an unprecedented array of trans-linked 6/6/6/7/7/6/6/8/6/6/6-membered rings, one 6-lactone and ten ether rings, leading to a stiff ladderlike linear structure. The structure of BTX-A C₄9H₇₀O₁₃(2), recently determined by X-ray crystallography, has an even more unique oxacarbocyclic skeleton made up of 5/8/6/7/9/8/8/6/6/6-membered rings. An independent study based solely on spectroscopic data, namely NMR and MS has led to the same structure except for an error in the configuration of one methyl group (at C-6). It was possible to construct the entire skeleton of BTX-A from the NMR data and MS of two derivatives. Two general fragmentation patterns in the MS of brevetoxin derivatives were recognized, and it was these patterns, assisted by NMR data, which enabled one to reconstruct the structure of brevetoxin A in a logical manner.