1996 Fiscal Year Final Research Report Summary
Molecular Design of Active Oxygen Scavengers Based on Chemical Reactivity of Vinylcyclopropanes
| Project/Area Number |
07672423
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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 |
医薬分子機能学
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
KATAOKA Tadashi Gifu Pharmaceutical Univ., Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00082975)
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| Co-Investigator(Kenkyū-buntansha) |
NOZAKI Masakatsu Research Institute for Production Development, Researcher, 研究員 (30021380)
WATANABE Shin-ichi Gifu Pharm. Univ., Res. Assoc., 薬学部, 助手 (40275095)
IWAMA Tetsuo Gifu Pharm. Univ. Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (10254252)
SHIMIZU Hiroshi Gifu Pharm. Univ., Faculty of Pharmaceutical Sciences, Associate Prof., 薬学部, 助教授 (00082983)
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| Project Period (FY) |
1995 – 1996
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| Keywords | vinylcyclopropane / sulfonium salt / sulfur ylide / sulfur heterocycle / active oxygen scavenger |
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| Research Abstract |
1. Synthesis of Vinylcyclopropane Derivatives : Dihydrothiopyran derivatives, prepared by cycloadditions of alpha-chloro sulfides with some 1,3-butadienes, were treated with a base to form the vinylcyclopropanes. We synthesized various vinylcyclopropane derivatives with captodative groups (an electron-withdrawing group and a sulfannyl group), in which some are spiro-bound with a 1,4-benzo-thiazin-3-one ring.
2. Reactions of Vinylcyclopropane Derivatives : Reactions of the vinylcyclopropanes with p-toluenesulfonic acid caused the ring-opening of a cyclopropane and a novel 1,5-sulfanyl group rearrangement to give diene derivatives. Thermal reaction of benzothiazine-spiro-vinylcyclopropane afforded a ring-expanded product, benzo-thiazinone-spiro-cyclopentene. Benzenethiol radically added to the vinylcyclopropanes to give 4-phenylthiobut-2-enylbenzothiazinone. Radical reactions of the benzothiazinone-spiro-vinylcyclopropanes with oxygen, alkenes and alkynes were initiated by phenylselenyl radical, and gave dioxolanes, cyclopentenes and cyclopentadienes in good yields, respectively.
3. In rabbit peritoneal polymorphonuclear leukocytes, the effect of the cyclopropane compounds on superoxide production was evalutated by chemiluminescence method using a specific superoxide probe, cypridina luciferin. Some compounds significantly inhibited superoxide generation induced by f-MLP in the dose dependent manner without change of viabilities and also suppressed active oxygen generation in a cell-free hypoxanthine-xanthine oxidase system. A series of the benzothiazinone vinylcyclopropane derivatives may be useful as a potentialscavenger of superoxide anion in vivo.
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