2005 Fiscal Year Final Research Report Summary
Synthetic studies of yessotoxin aiming at biological functions
| Project/Area Number |
15350024
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Organic chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
OISHI Tohru Osaka University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (90241520)
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| Project Period (FY) |
2003 – 2005
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| Keywords | synthetic chemistry / ladder-shaped polyether / natural products / convergent synthesis / total synthesis / α-cyano ether / natural toxin / yessotoxin |
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| Research Abstract |
Yessotoxin (YTX) is a marine polyether toxin produced by the dinoflagellate Protoceratium species. The broad spectrum of biological activities of YTX, coupled with the fascinating arched molecular structure, prompted us to target its synthesis. A convergent method for synthesizing 6/n/6/6 (n = 7, 8) tetracyclic ether system via two-ring construction of the central n/6 ring system was developed. The key steps of the present synthesis involve a ring-closing metathesis reaction for the construction of the seven- and eight-membered rings, and reductive etherification for the tetrahydropyrans. Unification of the two fragments through acetal formation, followed by regioselective cleavage of the acetal using TMSCN/TMSOTf in the presence of 2,6-di-tert-butyl-4-methylpyridine, afforded the α-cyano ether, of which the nitrile group was manipulated to give the precursors of the ring-closing reactions. The methodology was successfully applied to the convergent synthesis of the CDEF and FGHI ring systems via two-ring construction of the central DE and GH rings, respectively. The synthesis features convergent coupling of the diol and the aldehyde to form α-cyano ethers via acetal formation followed by ring closing metathesis and reductive etherification to construct the oxocane ring G and tetrahydropyran ring H, respectively. The β-methyl group on the G ring was stereoselectively introduced by alkylation of the corresponding ketone. Synthesis of a 6/6/6 tricyclic ether system corresponding to the ABC ring fragment of YTX has been achieved via coupling of a triflate and a 2-lithiofuran followed by intramolecular hetero-Michael addition. The IJ ring fragment of YTX was readily synthesized via successive Sharpless epoxidation and 6-endo cyclization of the resulting vinyl epoxide.
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