| Project/Area Number |
12672049
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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 |
Chemical pharmacy
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
NEMOTO Hideo TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY, Faculty of Pharmaceutical Sciences Full Professor, 薬学部, 教授 (60006351)
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| Co-Investigator(Kenkyū-buntansha) |
TOYOOKA Naoki TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY, Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (10217565)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | halenaouinol / sodium salt of sulfate / anti-virus activity / o-quinozimethane / benzocyclobutene / dihydrofuran / retro-electron-demanded Diels-Alder reaction / Sendai virus / 多環系天然物 / 分子内環化付加反応 / 四環系化合物 / アマンタジン / フラン環 / 抗ウィルス剤 |
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| Research Abstract |
Halenaquinol and sodium salt of its sulfate were isolated from the Okinawan sponge Xestospongia sapra by Kitagawa and co-workers in 1985. These interesting marine natural products possess the significant biological activities such as cytotoxic, antibiotic protein tyrosine kinase inhibitory activities, especially, the sodium salt of sulfate showed unique anti-virus activity. We designed the furan-fused polycyclic compound based on the structure of sodium salt of sulfate as a new type of anti-virus agent, and applied the o-quinozimethane chemistry as the key step for the construction of the above polycyclic ring system. The thermal reaction of the benzocyclobutenes, precursors of oquinozimethane, proceeded nicely to give the intramolecular [4+2] cycloaddition products as a single isomers. The stereochemistry at the newly formed quartanary benzylic and dihydrofuran position was determined to be cis form by an X-ray analysis. This stereoselectivity could be rationalized in term of secondary orbital effect between the electron deficient o-quinozimethane ring and electron rich furan ring in the retro-electron-demanded Diels-Alder reaction. Consequently, the reaction proceeded via the endo transition state to afford the cis products. Among the compound synthesized above, the TIPS derivative showed significant activity against Sendai virus, and inhibited the growth of the virus at the concentration more than 1.25μg/mL.
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