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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 忻凌偉 | |
dc.contributor.author | Yi-Ying Lin | en |
dc.contributor.author | 林宜穎 | zh_TW |
dc.date.accessioned | 2021-06-08T00:06:49Z | - |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-13 | |
dc.identifier.citation | 第一部分 乙二型興奮劑檢驗標準品之合成
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17323 | - |
dc.description.abstract | 第一部分 乙二型興奮劑檢驗標準品之合成
近年在臺灣發現以化合物1 (飆妥巴胺,buctopamine) 或化合物2 (苯乙胺醇A,phenylethanolamine A) 違法替代萊克多巴胺 (ractopamine) 作為「瘦肉精」。因此,本研究旨在合成高純度化合物1及化合物2供定性定量檢驗之標準品。化合物1由 4-hydroxyacetophenone經四步合成,總產率為50%;而化合物2由1-methyl-3-phenyl-propylamine經三步合成,總產率為30%。 第二部分10-Desmethyltetrabenazine (10-dmTBZ) 衍生物之合成及藥理活性研究 Tetrabenazine 是第一個也是唯一用於治療亨丁頓氏症的藥物,其右旋化合物藥效較左旋化合物強,在體內代謝成具活性之dihydrotetrabenazine。化合物(+/-)-3以(+)-2,3-dibenzoyl tartaric acid進行光學分割可得到化合物(+)-3;而隨之留下的化合物(-)-3,可經由異構化反應再次得到(+/-)-3。以化合物(+)-3為起始物,可合成得到化合物(+)-4、(+)-5與(+)-6。化合物(+/-)-7經還原反應可得到化合物(+/-)-C8。在這些10-dmTBZ衍生物中,化合物(+)-3、(+)-4及(+)-6對於第二型囊泡單胺轉運體有高親合力(Ki < 10 nM)。此外,由動物行為測試中發現,(+)-3可有效減低對小鼠自我給予安非他命之行為。 | zh_TW |
dc.description.abstract | Part 1 Synthesis of Potential beta-2 Receptor Agonists as Reference Standards
Recenly, compound 1 (buctopamine) and compound 2 (phenylethanolamine A) were illegally used as alternatives of ractopamine for growth promotion of livestock in Taiwan. Therefore, it is necessary to obtain compound 1 and compound 2 in high purity as reference standards for qualitative and quantitative analysis. Starting from 4-hydroxyacetophenone, compound 1 was prepared in four steps in an overall yield of 50%. Compound 2 was prepared from 1-methyl-3-phenyl-propylamine in three steps in an overall yield of 30%. Part 2 Synthesis and Pharmacological Activities of 10-Desmethyltetrabenazine (10-dmTBZ) Derivatives (+/-)-Tetrabenazine ((+/-)-TBZ) was the first and only drug used clinically to treat Huntington’s disease. The (+)-TBZ was more potent than (-)-TBZ and dihydrotetrabenazine (DTBZ) was the major active metabolite of TBZ. Compound (+)-3 was obtained by optical resolution of (+/-)-3 with (+)-2,3-dibenzoyltartaric acid, and (-)-3 could be epimerized to give (+/-)-3. Compounds (+)-4, (+)-5 and (+)-6 were synthesized starting from (+)-3. The (+/-)-7 was reduced to afford (+/-)-8. Among these 10-dmTBZ derivatives, (+)-3, (+)-4 and (+)-6 had high binding affinity to VMAT2 (Ki < 10 nM). It is found that (+)-3 effectively decreased d-methamphetamine self-administration in mouse behavior study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T00:06:49Z (GMT). No. of bitstreams: 1 ntu-102-R00423001-1.pdf: 5892127 bytes, checksum: c57a78bd276faa5d32a4a81b141cae24 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員審定書 I
中文摘要 II 英文摘要(Abstract) IV 英文縮寫表 VI 總目錄 VII 圖目錄 IX 表目錄 IX 路徑目錄 X 第一部分 乙型受體素檢驗標準品之合成 1 1. 緒論 1 1.1 乙型受體素簡介 1 1.2 瘦肉精的法規規定 2 1.3 飆妥巴胺的鑑別 4 1.4 苯乙醇胺A簡介 5 2. 研究目的 5 3. 結果與討論 5 3.1 合成及純化化合物1 5 3.1.1 化合物12之合成 6 3.1.2 化合物13之合成 6 3.1.3 化合物1之合成與再結晶純化 7 3.2 合成及純化化合物2 7 3.2.1 化合物15之合成純化 7 3.2.2 化合物2之合成與純化 11 4. 結論 12 參考文獻 13 第二部分 10-Desmethyltetrabenazine衍生物之合成及藥理活性研究 15 1. 緒論 15 1.1 簡介Tetrabenazine 15 1.2 製備單一光學活性之TBZ或其衍生物 16 1.3 本實驗室之前針對tetrabenazine衍生物之光學分割相關的研究 16 2. 研究目的 17 3. 結果與討論 18 3.1 化合物3、7之合成與結構確認 22 3.2 化合物(+/-)-3之光學分割 22 3.3 化合物(+)-4、(+)-5之合成與結構確認 23 3.4 化合物(+/-)-8之合成與結構確認 25 3.5 化合物(+)-6之合成與結構確認 25 3.6 化合物3與7之異構化研究 26 3.7 藥理活性研究 29 3.8 理化常數測定 31 4. 結論 32 參考文獻 33 第三部分 實驗 35 1. 合成 35 1.1 試劑及溶劑來源 35 1.2 自製無水溶劑 37 1.3 一般儀器及方法 37 1.3.1 一般儀器 37 1.3.2 Method of purity determination by high performance liquid chromatography 39 1.3.3 Method of reaction monitor and purity determination by gas chromatography 40 1.3.4 Method of enantiomeric purity determination 41 1.3.5 pKa determination method 41 1.3.6 log P determination method 41 1.4 合成步驟及分析數據 44 2. 藥理 61 附表 63 附圖 65 | |
dc.language.iso | zh-TW | |
dc.title | 中樞神經興奮性化合物之合成研究 | zh_TW |
dc.title | Study on Synthesis of Central Nervous System Stimulating Agents | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 王光昭,陳基旺,孔繁璐 | |
dc.subject.keyword | 飆妥巴胺,苯乙胺醇A,10-demethyltetrabenazine,光學分割,第二型單胺轉運體, | zh_TW |
dc.subject.keyword | buctopamine,phenylethanolamine A,10-demethyltetrabenazine,optical resolution,VMAT2, | en |
dc.relation.page | 141 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2013-08-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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