| Project/Area Number |
14208075
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Tokushima Bunri University |
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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) |
IMAGAWA Hiroshi Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (80279116)
TAKAO Hiroko Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (00279118)
杉原 多公通 徳島文理大学, 薬学部, 助教授 (40222054)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2005: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2004: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2003: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2002: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
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| Keywords | activation of immune system / anti-tumor activity / trehalose derivative / glycolipid / mercuric triflate-catalyzed reaction / hydration of alkyne / enyne cyclization / sterol biosynthesis / 抗腫瘍性 / トレハロースジエステル / がん転移阻害作用 / 触媒的環化反応 / 生合成類似タンデム環化反応 / TDCM / 水銀トリフラート / 免役活性化 / 有機合成 / 不斉合成 / 結核菌関連細胞表層糖脂質 |
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| Research Abstract |
Cell surface glycolipids of Mycobacterium tuberculosis with more the 60 carbons fatty acid residue exhibits anti-tumor activity based on the activation of immune systems, however significant toxicity retards its medical applications even though a significant research have been carried out for many years particularly by Yamamura school of Osaka University. We have interested in a shorter fatty acid analogues, TDCM, obtained from cell surface of diphteriae, and achieved the synthesis of four stereoisomers (RR, RS, SR and SS) based upon the stereogenic centers of its fatty acid residue. First, we identified that the natural product is the RR isomer, and then synthetic SS isomer showed significant anti-tumor activity by activating macrophages without showing toxicity (neither in vivo nor cytotoxicity). Then we achieved the synthesis of a large numbers of analogues after establishing the in vitro assay systems. We are currently applying the patent by developing anti-tumor active compounds t
… More
hat shows activation of IL-6.
On the other hand we have been working on the development of new synthetic methodologies. In 1983, we developed highly efficient olefin cyclization agent, Hg(OTf)_2. In 2002, the year this research project started, we hound that Hg(OTf)_2 shows powerful catalytic activity for the hydration of terminal alkynes leading to methyl ketones. The process is clean catalytic reaction and dose not produce methylmercuric chloride that induced Minamata decease in 1952. We have further demonstrated that Hg(OTf)_2-catalyzed hydroxylative 1,6-enyne cyclization to give exomethylene five-membered ring products, cyclization of 1-alkyn-5-ones leading to 2-methylfurans, arylalkyne cyclization leading to dihydronaphthalene derivatives, biomimetic tandem cyclization of alkynyl alkenyl aryl derivative to give polycarbocycles, and the reaction of propargyl acetate with water affording vinyl ketones. These reactions likely involve a protodemercuration step of the vinylmercury intermediate, which is induced by in situ-generated TfOH.
We have also been investigating the area of sterol biosynthesis after elucidation of stepwise mechanism for oxidosqualene cyclization. Recently we found that the energetically disfavored ring enlargement of pre-C-ring tert-cation to six-membered ring sec-cation is overcome by conformation change controlled by counteranions. This is the first example of the anti-Markovnikov rearrangement observed in cation chemistry, and this is the first example that the cation conformational calculation in the presence of counteranion. Less
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