2007 Fiscal Year Final Research Report Summary
Elucidation of food chain mechanism and metabolic pathway of tetrodotoxin by uisng its synthetic probe
| Project/Area Number |
18510182
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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 |
Living organism molecular science
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| Research Institution | Nagoya University |
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Principal Investigator |
NISHIKAWA Toshio Nagoya University, Graduate school of Bioagrucultiral Sciences, Associate Professor (90208158)
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| Project Period (FY) |
2006 – 2007
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| Keywords | tetrodotoxin / organic synthesis / isotope labeling / food chain / biosynthesis / metabolic pathway / Diels-Alder reaction / Overman rearrangement |
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| Research Abstract |
Purpose of this research is to synthesize tetrodotoxin derivatives labeled with stable-isotope, which is indispensable for elucidation of the food chain mechanism and its biosynthetic study. We have synthesized 5-deoxytetrodotoxin and 5,6,11-trideoxytetrodotoxin, the most plausible precursors of tetrodotoxin, as shown below.
We have successfully developed a practical synthetic route of a new common synthetic intermediate bearing a hydroxyl group at the C-11 position, which actually allowed preparing 100 g scale of the intermediate. The synthesis of 5-deoxytetrodotoxin started from the new common intermediate. Hydroxylation at the C-8 position was carried out by neighboring group participation of trichloroacetamide, and then the configuration was inverted by oxidation-reduction of the resulting hydroxyl group. Cyclic olefin was selectively epoxidized with MCPBA, the vinyl group was ozonized to an aldehyde. Addition of acetylene, a carboxylic acid equivalent, was best carried out by lithium acetylide to give a propargyl alcohol in a highly stereoselective manner. After protective group manipulation, the alkyne moiety was cleavaged with RuO4 to generate an a-hydroxyl carboxylic acid, which spontaneously opened the epoxide to furnish lactone product.
The remaining task is installation of guanidinin group and cleavage of 1,2-glycol of the lactone intermediate. We will accomplish the synthesis of 5-deoxytetrodotoxin and then 5,6,11-trideoxytetrodotoxin labeled with stable isotope such as ^15N and ^13C atoms
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[Journal Article] Synthesis of O-Analogues of C-Mannosyltryptophan, a Novel C-Glycosylamino Acid Found in Proteins2006
Author(s)
Nishikawa, T., Koide, Y., Kanakubo, A., Yoshimura, H., Isobe, M
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Journal Title
Organic Biochemical Chemistry 4
Pages: 1268-1277
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] One-Pot Transformation of Trichloroacetamide into Readily Deprotectable Carbamates2006
Author(s)
Nishikawa, T., Urabe,D., Tomita, M., Tsujimoto, T., Iwabuchi, T., Lobe, M
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Journal Title
Organic Letters 8
Pages: 3263-3265
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Syntheses of Naturally Occurring Terphenyls and Its Related Compounds2006
Author(s)
Sawayama, Y., Tsujimoto, T., Sugino, K., Nishikawa, T., Isobe, M., Kawagishi, H
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Journal Title
Bioscience, Biotechnology & Biochemistry 70
Pages: 2998-3003
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Synthetic studies on 5-deoxytetrodotoxin2007
Author(s)
Y. Satake, H. Arald, T. Nishikawa, M. Isobe
Organizer
Annul Meeting of Janan Society of Bioscience, Biotechnology, and Agrochemistry, the Chubu Branch
Place of Presentation
Kasugai (Japan)
Year and Date
20070921-22
Description
「研究成果報告書概要(欧文)」より
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