Maitotoxin (MTX), produced by the dinoflagellate Gambierdiscus toxicus, is the most toxic and largest non-biopolymer known to date. The elucidation of its complete structure with the absolute configuration has been regarded as one of the most exciting challenges in natural products chemistry. The gross structure and stereochemistry of the fused rings as well as directly connected ether rings were elucidated on the basis of extensive 2,3D NMR analyses and MS/MS experiments. We have recently succeeded in determination of the relative configuration along the entire polyether entity of MTX encompassing ether rings A through F. Herein we report the determination of the remaining configuration along both terminal chains and the absolute configuration of MTX. The relative configurations of the stereogenic centers in the C1-C15 acyclic terminal chain of MTX were elucidated by (1) extensive conformational analysis using ^3JH,H and ^<2,3>JC,H coupling constants obtained by a contemporary NMR technique, and (2) synthesis of model compounds 2A and 2B furnished with thus determined relative configurations, and comparison of their ^1H and ^<13>C NMR data with those for the corresponding portion of MTX, concluding that 2A represents the relative stereochemistry of the C5-C15 portion of MTX. The relative stereochemistry between C136 and C138 in the another terminal acyclic chain was unambiguously assigned on the basis of the ^3JH,H and ^<2,3>JC,H data. The stereochemical relationships among C134, C135, and C136 were also deduced from the similar NMR analysis and confirmed by the comparison of the synthesized model compound 24 with MTX in their ^1H NMR. In order to determine the absolute configurations along with the relative configuration between C 138 and C139, which was not deduced by NMR due to signal broadening, we synthesized the four stereoisomers 25a-d possible for 3,4-dimethy1-6-hepten-l-ol and compared them with a degraded fragment of a natural product by GC with chiral column to identify 25a as the natural diastereo- and optical isomer, thus establishing the 138R,139S configuration of MTX. The present results, together with the previously reported stereochemical assignments, allowed us to determine the complete absolute stereochemistry of MTX to be represented by structure 1.
