1999 Fiscal Year Final Research Report Summary
Synthetic Study of Taxol by a Biomimetic Aproach
| Project/Area Number |
09480146
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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 |
Bioorganic chemistry
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| Research Institution | Faculty of Pharmaceutical Sciences |
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Principal Investigator |
NISHIZAWA Mugio Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40137188)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAO Hiroko Tokushima Bunri University, Facultry of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (00279118)
IMAGAWA Hiroshi Tokushima Bunri University, Facultry of Pharmaceutical Sciences, Instuctor, 薬学部, 助手 (80279116)
SUGIHARA Takumichi Tokushima Bunri University, Facultry of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40222054)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Taxol / Cancer / Hg(OTf)ィイD22ィエD2 / Cyclization / Rearrangement / Bicyclo〔9. 3. 1〕pentadecatriene / McMurry Reaction / Cation |
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| Research Abstract |
Taxol is a diterpene derivative employed as a significant clinical application against human cancers such as breast, ovarian, and lung cancer. Since the supply of taxol is a serious problem, numerous synthetic studies have been carried out and several groups have accomplished total syntheses. We have developed an efficient olefin cyclization agent, mercuric triflate Hg(OTf)ィイD22ィエD2, and applied it for the syntheses of a variety of carbocyclic terpenoids. We have been interested in the synthetic application of Hg(OTf)ィイD22ィエD2 for the construction of a taxane skeleton according to a biomimetic entry. Through out in this study, it was demonstrated that the A-ring synthone of taxol was efficiently synthesized by Hg(OTf)ィイD22ィエD2 induced cyclization of homogeranyl acetate as the key step. Conventional introduction of the side chain moiety and McMurry cyclization of the derived keto aldehyde afforded diols with a bicyclo〔9. 3. 1〕pentadecatriene skeleton. Transannular cyclization of selected 2α-p-nitrobenzoate with Hg(OTf)ィイD22ィエD2 was examined and a very complicated rearranged organomercuric product was isolated. The mechanism of the totally unexpected rearrangement is proposed. Then we focussed the synthesis of the key intermediate C-8 cation possible to lead biosynthetic transannular cyclization.
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