26 ガンビ***ールの合成研究(口頭発表の部)

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Gambierol (1) is a marine polycyclic ether isolated as a toxic constituent from cultured cells of the ciguatera causative dinoflagellate, Gambierdiscus toxicus. This compound shows toxicity against mice (LD_<50>, 50μg/kg), and the symptoms resemble those caused by ciguatoxins. The unique structural features have attracted the attention of synthetic chemist. We have already succeeded in the convergent synthesis of the CDEFG ring system (8) via the intramolecular allylation of the α-acetoxy ether 4 and subsequent ring-closing metathesis. Encouraged by this result, we started the total synthetic study of gambierol (1). Treatment of the cyclization precursor 15, prepared from the ABC ring segment 10 and FGH ring fragment 11, with MgBr_2・OEt_2 gave the desired product 9 and its C16 epimer 16 in 22% and 47% yield, respectively. The yield of 9 was improved by using monochloroacetoxy group as a leaving moiety. Thus, the reaction of 19 gave 9 and 16 in 30% and 48% yield, respectively. The diene 9 was subjected to ring-closing metathesis with 7 to give 20 in 84% yield. The octacyclic compound 20 was converted to 28 by several steps. We next examined the construction of the triene side chain. Although the Stille coupling of 29 and 30 gave the cross-coupling product 31 in an allowable yield (63%), the reaction was very slow (4 days). After unfruitful attempts, we succeeded in developping an efficient method for the stereoselective synthesis of Z-iodoolefin 33. Treatment of 32 with Zn-Cu and AcOH gave 33 as a single stereoisomer in 80% yield. As expected, the reaction of 33 and 30 was very fast. The triene 31 was obtained in 95% yield after 1.5h. Similaly, the iodoolefin 35, prepared from 28, was converted to the fully protected gambierol 36 in good yield. The final deprotection of 36 giving 1 is currently under way.
天然有機化合物討論会の論文
2002-09-01

26 ガンビ***ールの合成研究(口頭発表の部)

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