STRUCTURE AND PARTIAL STEREOCHEMICAL ASSIGNMENTS FOR MAITOTOXIN, THE MOST TOXIC AND LARGEST NATURAL NON-BIOPOLYMER

Maitotoxin (MTX), with a molecular weight of 3422, was first discovered as one of the toxins responsible for ciguatera, a seafood poisoning caused by coral reef fish. For this study MTX was isolated from cultured cells of the ciguatera-causative dinoflagellate Gambierdiscus toxicus and was subjected to extensive 2D NMR measurements. A large portion of the structure was shown to be a brevetoxin-type polyether. Precise structural assignments were, however, unsuccessful, chiefly due to extensive overlapping of H-1 and C-13 NMR signals even in the 2D spectra. MTX was treated with NaIO4 followed by reduction with NaBH4, resulting in cleavage of the molecule into two major parts, fragments A and B, together with a small C-9 fragment. Fragments A and B had molecular weights of 964 and 2328. Their structures were elucidated by extensive 2D NMR and collisionally activated dissociation (CAD) MS/MS experiments. Reassembling the three fragments led to the complete structure of MTX (C164H256O68S2Na2), encompassing two sulfate esters, 28 hydroxyls, and 32 ether rings. Relative stereostructure was partly assigned and comprised trans-fused polycyclic ethers except for rings L/M and N/O that are cis-fused. The stereochemistry of the acyclic parts, C5-C14, C36-C37, C64-C66, and C135-C139, remains to be determined.