STRUCTURE OF MAITOTOXIN, THE MOST TOXIC A ND LARGEST NATURAL NON-BIOPOLYMER

Maitotoxin was first discovered as one of the causative toxins respons ible for ciguatera, which is a form of seafood poisoning prevalent in coral reef area. The structure (1) has been elucidated to be a polyket ide compound with a molecular weight of 3422 Da, which makes the toxin the largest natural non-biopolymer known to date. The structure is pa rtly reminiscent of brevetoxins or ciguatoxins, which comprise trans-f used polycyclic ethers, though maitotoxin possesses about three times as many ether rings as does brevetoxin B. In this paper we review the structure elucidation of maitotoxin with the main focus on spectroscop ic methodology, particularly on tandem mass spectrometry (MS/MS), thre e-dimensional NMR spectra, and stereostructural analysis using NOE and (3)JH,H data coupled with force field calculations. Collisionally Act ivated Dissociation (CAD) MS/MS spectra with a negative FAB ionization were successfully measured for fragment B (MW.2328 Da) of maitotoxin and revealed fragment ions from which the sizes and sequences of ether rings easily were derived. Three dimensional NOESY-HMQC with pulse fi eld gradient was determined for a C-13-enriched specimen (at about 4%) and provided 64 C-13-edited NOESY spectra, some of which brought esse ntial NOE information regarding the mode of ether cyclization and ster eochemistry.