31 アセチレンコバルト錯体を活用したシガトキシンの合成研究(口頭発表の部)

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Ciguatoxin (1) is a principal toxin of ciguatera which is one of the most wide spread seafood poisonings. Our concept for the total synthesis toward Ciguatoxin (1) is based on acetylene dicobalthexacarbonyl complex-mediated ether-cyclizations. The reaction proceeds via a dicobalthexacarbonyl complex-stabilized cationic intermediate, which called Nicholas effect, subsequently undergoes endo cyclization to give a syn product thermodynamically. We have explored various decomplexation methods of the endo-acetylene cobalt complex. The retrosynthetic analysis toward ciguatoxin is revealed that the A, F, and G ring would be cyclized at the latest stage after the coupling between acetylene of left segment 11 and aldehyde of right segment 12. The right segment would be divided further three subsegments (16, 17 and 18). Synthesis of left segment 11 was started from 19. The methylketone moiety of 19 was protected as 2-naphtylmethyl ether. The modification of E-ring was proceeded by following steps: epoxidation of vinylsilane, Peterson reaction, ring opening of epoxysilane, inversion of hydroxyl group to afford 11. Subsegment 17 was prepared through heteroconjugate addition reaction of excess amount of lithium acetylide and vinyl sulfone 23. Reduction of the desilylated product 26 using SmI_2 gave subsegment 17. After coupling between 17 and 18, the coupling product was cyclized via acetylene cobalt complex followed by dihydroxylation and spiroketalization to give JKLM-ring fragment. Sonogashira coupling of vinyltriflate 31 with acetylene 16 followed by I-ring cyclization to cyclic cobalt complex 33. Intramolecular 1.4-addition of enone afforded H-ring cyclized product 35. The cyclic ketone 35 was transformed into endo-cyclic olefin 36 and subsequent reduction with Crabtree catalyst to give 37 as a single isomer. Segment coupling between 11 and 12 followed by F-ring cyclization to 39. The cyclic cobalt complex 39 was converted into corresponding ketone via ligand exchange with dppm. The hydroxyketone was cyclized by reductive etherification to give BCDEFGHIJKLM-ring 41 in moderate yield. Construction of A-ring to 1 is now underway.
天然有機化合物討論会の論文
2007-08-24

31 アセチレンコバルト錯体を活用したシガトキシンの合成研究(口頭発表の部)

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