yessotoxin and adriatoxin

Yessotoxin and adriatoxin are members of the polycyclic ether family of marine natural products. Outlined in this article is our synthetic approach to two subunits of these targets. Central to our strategy is a coupling sequence that employs an olefinic-ester cyclization reaction. As outlined, this sequence was used in two coupling sequences. First, it was used to merge the A, B- and E, F-bicyclic precursors and in the process generate the C- and D-rings. Second, it was used to couple the F- and I-rings while building the eight-membered G-ring and subsequently the H-ring pyran.

Topics: Animals; Biological Products; Chemistry Techniques, Synthetic; Cyclization; Dinoflagellida; Molecular Structure; Mollusk Venoms; Oxocins; Pectinidae

Adriatoxin-B (ATX-B) is the first C(13) terminal truncated YTX analogous metabolite that was isolated from large-scale cultures of the dinoflagellate Protoceratium reticulatum. The structure and conformational behavior of ATX-B was elucidated by a combination of NMR spectroscopy experiments and a conformational analysis. The isolation of this metabolite, which possesses a clear structural relationship with adriatoxin, supports the idea that the real source of these cut down substances is in the microalgae and not in the mollusks, via metabolic degradation like it has been assumed until now.

Topics: Animals; Chromatography, High Pressure Liquid; Dinoflagellida; Magnetic Resonance Spectroscopy; Marine Toxins; Mollusk Venoms; Oxocins; Pyrans; Solid Phase Extraction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The combination of a trimethylsilyl group, a Brønsted base, a fluoride source, and a hydroxylic solvent enables the first construction of the tetrad of tetrahydropyran rings found in the majority of the ladder polyether natural products by way of a cascade of epoxide-opening events that emulates the final step of Nakanishi's proposed biosynthetic pathway. The trimethylsilyl group disappears during the course of the cascade, and thus these are the first epoxide ring-opening cascades that afford ladder polyether subunits containing no directing groups at the end of the cascade.

Topics: Ciguatoxins; Epoxy Compounds; Ethers, Cyclic; Furans; Molecular Conformation; Mollusk Venoms; Oxocins; Polycyclic Compounds; Polymers

Convergent synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, marine polycyclic ether toxins causative of diarrheic shellfish poisoning, has been accomplished. The A-ring fragment was constructed by coupling of an appropriately functionalized sulfonyl-stabilized oxiranyl anion and a triflate prepared from an erythritol derivative. An iterative protocol of the oxiranyl anion strategy was also applied for the construction of the DEF-ring fragment. The triflate derivatives of the A-ring and the DEF-ring fragments were connected with lithium acetylide. The resulting acetylene derivative was further transformed into the hexacyclic ABCDEF fragment via oxidation of the acetylene unit to 1,2-diketone, double methyl acetal formation, and reductive etherification.

Topics: Ethers; Ethers, Cyclic; Lithium; Molecular Structure; Mollusk Venoms; Oxocins; Spectrum Analysis