| Project/Area Number |
61571000
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
HARAYAMA Takashi Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 助手 (30025712)
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| Co-Investigator(Kenkyū-buntansha) |
FUMIO Yoneda Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 教授 (80040327)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Damage of nucleic acid / Thymidine / Thymidine bromohydrins / Thymidine epoxide / ラミジンエポキシド / 核酸の修復 / 生体内酸化モデル反応 / チミン / チミンエポキシド / チミジンエポキシド / 求核剤 / 異性化 |
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| Research Abstract |
Much attention has been forcused on the oxidation of nucleic acids and related compounds in relation to mutagenesis, carcinogenesis and aging. Research concerning with oxidation of thymidines were carried out ot give the following results.
1. Oxidation of thymine derivatives with m-chloroperbvenzoic acid gave cis-glycol ester and oxidation with KO_2 gave five-membered compounds. A mechanism for formation of these oxidation products via epoxide is presented.
2. Reactions of dl-1,3-dimethylthymine epoxide with amines and L-amino acid derivatives were investigated. The stereo-structures of the products were eluciadated by X-ray analysis and by isomerization of the trans adducts to the cis adducts by using BF_3・Et_2O. A mechanism for the isomerization is presented.
3. Reaction of thymidine epoxides with amine and L-amino acid ethyl esters was investigated and the stereo-structures of products were determined. In this connection, it was found that thymidine bromohydrins, which were damaged products of thymidines were repaired with sunlight or heat via a radical mechanism to regenerate the thymidines.
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