2005 Fiscal Year Final Research Report Summary
Synthetic studies on marine polycyclic ethers and their derivatives
| Project/Area Number |
15390009
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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 |
Chemical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
NAKATA Tadashi Tokyo University of Science, Faculty of Science, Department of Chemistry, Professor, 理学部, 教授 (50087524)
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| Project Period (FY) |
2003 – 2005
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| Keywords | brevetoxin / gambierol / yessotoxin / gymnocin / samarium diiodide / reductive cyclization / Barbier reaction / acyloin condensation |
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| Research Abstract |
Since the first isolation of brevetoxin-B in 1981, many marine polycyclic ethers, exemplified by brevetoxins, gambierol, and maitotoxin, have attracted the attention of numerous synthetic organic chemists due to their synthetically challenging complex structures and their potent bioactivities. The structural feature of these natural products is a trans-fused polycyclic ether ring system. Thus, various methods for construction of cyclic ether ring system have been extensively studied and the total synthesis of marine polycyclic ethers have been studied. In this research project, we have developed new methods for the construction of polycyclic ethers and accomplished total and partial synthesis marine polycyclic ethers.
Several efficient methods for the construction of trans-fused polycyclic ethers were developed ; (1) a convergent method based on an intramolecular Barbier reaction of iodo ester with SmI_2-NiI_2 and Lewis acid-promoted slime reduction of hemiacetal. (2) an alternative con
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vergent method based on an intramolecular Barbier reaction of iodo ester with t-BuLi or n-BuLi as a key step. (3) a new method for synthesis of cyclic ether based on acyloin condensation. (4) stereoselective method for the synthesis of 2,6-syn-2,3-trans-and 2,6-syn-2,3-cis-tetrahydropyrans based on SmI_2-induced reductive cyclization of (E)-and (Z)-β-alkoxyvinylsulfones with aldehyde.
Total and partial syntheses of marine polycyclic ethers were extensively investigated. Total synthesis of brevetoxin-B was accomplished based on two-directional synthetic strategy using SmI_2-induced reductive cyclization of β-alkoxyacrylate. The ABCDE-ring, FGHIJ-ring, and K-ring of yessotoxin were synthesized based on two-directional strategy, convergent strategy, and endo-cyclization of epoxy alcohol, respectively. The synthesis of WXYZA'-ring of maitotoxin was accomplished based on SmI_2-induced reductive cyclization, endo-cyclization of epoxy alcohol. The synthesis of FGH-ring and KLMN-ring of gymnocin was accomplished based on SmI_2-induced reductive cyclizations using β-alkoxyacrylate and β-alkoxyvinylsulfone. The coupling of ABC-and EFG-rings of gambierol was accomplished based on an intramolecular Barbier reaction of iodo ester with SmI_2-NiI_2, and DEFG-ring was also synthesized. Less
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