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Volumn 48, Issue 16, 2009, Pages 2941-2945

Total synthesis of ciguatoxin

Author keywords

[No Author keywords available]

Indexed keywords

SYNTHESIS FEATURES; TOTAL SYNTHESIS;

EID: 70349917819     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200805996     Document Type: Article
Times cited : (61)

References (62)
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    • The critical oxidation of the acetylene-dicobalthexacarbonyl complexes that gave ketones was not highly reproducible (10-40, yield) when heated in the form of the hexacarbonyl ligand (see Ref, 12, Among various bidentate ligands examined, we found that the dppm ligand gave the best reproducibility with model compounds 40-75% yield; see Ref, 9
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    • This complication may result from the formation of a cluster between the anionic species and the polyether moieties in the molecule. This situation may be similar to a previous problematic case that we reported during the total synthesis of okadaic acid, a marine polyether, in the coupling between a sulfonyl carbanion and an aldehyde. In this case, changing the solvent from pure THF to Et2OM-hexane (3:2) resulted in dramatic reaction progress; however, this type of salt/solvent system was not successful for coupling in ciguatoxin; see: M. Isobe, Y. Ichikawa, D.-L. Bai, H. Masaki, T, Goto, Tetrahedron, 1987, 43, 4767-4776
    • 2OM-hexane (3:2) resulted in dramatic reaction progress; however, this type of salt/solvent system was not successful for coupling in ciguatoxin; see: M. Isobe, Y. Ichikawa, D.-L. Bai, H. Masaki, T.. Goto, Tetrahedron, 1987, 43, 4767-4776..
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    • After the eneyne coupling, the acetylene was converted into the dicobalthexacarbonyl complex 19 a, which was subjected to cyclization under acidic condition. The initial intermediate- where the allylic cation is located at C3-might be stabilized by the neighboring pivaloyl group at C2, and became reactive as intermediate 19 b by the addition of THF solvent.
    • After the eneyne coupling, the acetylene was converted into the dicobalthexacarbonyl complex 19 a, which was subjected to cyclization under acidic condition. The initial intermediate- where the allylic cation is located at C3-might be stabilized by the neighboring pivaloyl group at C2, and became reactive as intermediate 19 b by the addition of THF solvent.


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