| Project/Area Number |
17580099
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | RIKEN |
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Principal Investigator |
TAKAHASHI Shunya RIKEN, Molecular Characterization Team, Senior Researcher, 物質構造解析チーム, 先任研究員 (00202151)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | annonaceous acetogenins / intermolecular metathesis / pyragonicin / antiviral activity / macroviracin / intramolecular metathesis / バンレイシ科植物 / カムバリニン / β-アルコキシアクリレート / ヨウ化サマリウム |
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| Research Abstract |
We have developed new synthetic methods for the synthesis of fatty-acid derived natural products with biological activities, and achieved total syntheses of natural products as follows.
1. Total synthesis of antitumor annonaceous acetogenins.
In order to construct a tetrahydropyran (THP) ring that is regard as a characteristic structural feature of several annonaceous acetogenins, a SmI_2 mediated radical cyclization reaction of β-alkoxy acrylate was developed. First total synthesis of pyragonicin was accomplished by the Wittig reaction between a highly functionalized THP derivative synthesized by the Sm method and a γ-lactone. Furthermore a new method for construction of the carbon-backbone of annonaceous acetogenins was searched, and we found that an intermolecular olefin metathesis was suitable for such a purpose. This methodology was applied to preparation of a natural lactone obtained from Trichilia alaussenii and a second-generation synthesis of pyragonicin.
2. Synthetic studies on an antiviral macrodiolide, macroviracin A.
Macroviracin A bears a 42-membered macrodiolide core consisting of a C_<22> fatty acid dimer possessing D-glucose residues, and a long side chain attached to the core. The constitutive fatty acid derivative was synthesized by an intramolecular metathesis of a terminal olefin ester that was prepared from an olefin alcohol and an olefin carboxylic acid. On the other hand, an intermolecular metathesis of the terminal olefin ester provided the C_2-symmetric macrodiolide core of the antiviral agent in a single step.
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