Synthetic studies of polycyclic ether marine toxins

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Polycyclic ether marine toxins have interesting biological activities, such as neurotoxicity, diarrheic toxicity, and antifungal activity. In this project, synthetic studies of yessotoxin and adriatoxin, causative toxins of diarrheic shellfish poisoning were undertaken, and the following results were obtained.1. Convergent synthesis of 6-membered polycyclic ethersTwo 6-membered ethers were coupled with an acetylene unit, and the triple bond of the product was oxidized with ruthenium tetroxide to give a 1,2-diketone. The diketone was transformed into bis(methyl hemiketal) by treatment with an acid, which was then reduced with triethylsilane in the presence of TMS-triflate to give a tetracyclic polytetrahydropyran.2. Synthesis of the BCDE-ring system of yessotoxinSynthesis of a 6-6-6-7 tetracyclic polyether ring system was accomplished by starting from 6- and 7-membered ether rings and an acetylene unit by employing the convergent method stated above.3. Convergent synthesis of the ABCDEF-ring of yessotoxin and adriatoxinThe A-ring fragment with an acetylene side chain and the DEF-ring fragment with a trifluoromethanesulfonyl group on the D-ring were prepared based on an strategy of alkylation of an oxiranyl anion followed by 6-endocyclization. The synthesis of the ABCDEF-ring fragment of yessotoxin has achieved by coupling of both fragments, oxidation of the acetylene moiety to 1,2-diketone, bis(methyl acetyl) formation, and reduction.