博碩士論文 110223014 詳細資訊




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姓名 游雅筑(Ya-Chu Yu)  查詢紙本館藏   畢業系所 化學學系
論文名稱 碳酸銫介導正交性一鍋化合成 嘧啶衍生物用以建構新的功能化金屬配體
(A Cs2CO3-Mediated Orthogonal One-Pot Synthesis of Pyrimidine Derivatives Access to New Functionalized Metal Ligands)
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摘要(中) 嘧啶(pyrimidine)化合物由於它的生物活性及藥物臨床上的應用得到了許多關注,像是天然物維生素 B1、藥物司他夫定(stavudine)等都包含了嘧啶的結構,因此化學家致力於合成嘧啶的衍生物,過去所開發的方法大多需要金屬催化劑、嚴苛的反應條件及繁複的實驗步驟。為了克服這些問題,我們實驗室開發的碳酸銫介導正交性一鍋化合成嘧啶衍生物的方法,可以經由簡單、快速的在溫和反應條件下,從 5-溴-1,2,3-三嗪獲得 2-吡啶基嘧啶及 2-苯基嘧啶等具有獨特金屬螯合位的配體化合物,此類嘧啶配體過去用在金屬錯合物的並不多。在本論文中,我們利用上述簡單碳酸銫介導的方法,合成出具有功能化的苯基嘧啶及吡啶基嘧啶衍生物分別作為銥及釕金屬的配體,並透過疊氮-炔烴環加成反應合成針對細胞核、粒線體、及溶酶體等胞器靶向的金屬錯合物,作為細胞內胞器螢光成像探針; 另一方面,我們同時合成含硫醚基的金屬錯合物作為化學傳感器,希望用於細胞中作為偵測次氯酸螢光探針,藉由氧化硫醚基誘導發光的機制來分析細胞內次氯酸濃度。整體而言,我們利用 5-溴基 1,2,3-三嗪作為起始物,利用簡單碳酸銫介導的方法,合成的嘧啶化合物作為配體的策略可為金屬錯合物的合成應用提供廣泛的發展潛力。
摘要(英) Pyrimidine compounds have received widespread attention because of their biological activity and medical applications. Many natural products and drugs contain the pyrimidine in their core structures, such as vitamin B1 and stavudine. Although chemists are dedicated to developing
methods for synthesis of the pyrimidines, the problems encountered are the need for metal catalyst, harsh reaction conditions and complicated experiment steps. To overcome these issues, we developed a cesium carbonate-mediated method for the orthogonal one-pot synthesis of pyrimidine derivatives. Using this simple and fast approach under mild reaction conditions, we can prepare the phenylpyrimidines and pyridylpyrimidines as ligands with unique chelation
sites in metal complexes. Such pyrimidine compounds have been rarely used as ligands in metalcomplexes in the past. In this thesis, we have synthesized functionalized phenylpyrimidines and pyridylpyrimidines as ligands for iridium and ruthenium metals using this cesium carbonatemediated approach. In addition, we generated the nucleus, mitochondria and lysosome-targeted metal complexes as the bioimaging agents by using the azide-alkyne cycloaddition reactions. On the other hand, we also synthesized the thiolether-bearing metal complexes that can be used as chemosensors for HClO in cells. The qualitative analysis of the analyte can be carried out through the luminescence change of the metal complex. The success of the pyrimidine compound synthesized by our method as a metal ligand provides the potential for the application of metal complexes.
關鍵字(中) ★ 嘧啶
★ 細胞胞器靶向探針
★ 傳感器
關鍵字(英)
論文目次 目錄
摘要.............................................................................................................................................i
Abstract.......................................................................................................................................ii
誌 謝.........................................................................................................................................iii
目錄...........................................................................................................................................iv
圖目錄.......................................................................................................................................vi
簡稱用語對照表.....................................................................................................................viii
一、 緒 論..............................................................................................................................1
1-1 嘧啶(pyrimidine).........................................................................................................1
1-2 已開發的嘧啶合成方法.............................................................................................1
1-3 開發一鍋化合成嘧啶衍生物方法.............................................................................2
1-3-1 苯氧基(phenoxy)嘧啶衍生物的合成.............................................................2
1-3-2 苯硫基(phenylthiol)嘧啶衍生物的合成.........................................................3
1-4 嘧啶類化合物作為金屬配體.....................................................................................3
1-5 發光過渡金屬錯合物.................................................................................................4
1-6 發光過渡金屬錯合物在材料領域上的應用.............................................................5
1-6-1 過渡金屬錯合物作為 OLED 材料.................................................................5
1-6-2 過渡金屬錯合物作為 DSSC 材料 .................................................................6
1-7 過渡金屬錯合物在生物研究領域上的應用.............................................................7
1-7-1 過渡金屬錯合物作為藥物 .............................................................................8
1-7-2 基於過渡金屬錯合物的化學傳感器 .............................................................9
1-7-2.1 次氯酸(ClO−
)發光化學傳感器..........................................................10
1-7-2.2 過氧亞硝酸鹽(ONOO-
)發光化學傳感器......................................... 11
1-7-2.3 Cu2+發光化學傳感器..........................................................................12
1-7-3 生物成像探針 ...............................................................................................13
1-7-3.1 細胞內胞器探針 ................................................................................13
1-7-3.1.1 細胞核靶向探針 .....................................................................13
1-7-3.1.2 粒線體靶向探針 .....................................................................15
1-7-3.1.3 溶酶體靶向探針 .....................................................................16
1-7-3.1.4 內質網靶向探針 .....................................................................17
1-7-3.1.5 高爾基體靶向探針 .................................................................17
1-8 研究動機...................................................................................................................18
1-9 本論文錯合物分子設計...........................................................................................19
二、 實驗結果與討論............................................................................................................21
2-1 含嘧啶釕、銥金屬錯合物.......................................................................................21
2-2 嘧啶化合物的合成...................................................................................................23
2-2-1 化合物 3 的合成 ...........................................................................................23
v
2-2-2 化合物 5 的合成 ...........................................................................................24
2-2-3 化合物 20 的合成 .........................................................................................25
2-2-4 化合物 25 的合成 .........................................................................................25
2-2-5 化合物 32 的合成 .........................................................................................26
2-3 釕金屬錯合物的合成...............................................................................................26
2-3-1 疊氮化合物 7、8 的合成 .............................................................................27
2-3-2 化合物 11 的合成..........................................................................................28
2-3-3 化合物 12、13、14 的合成 .........................................................................28
2-3-4 化合物 16 的合成 .........................................................................................29
2-3-5 化合物 17、18、19 的合成 .........................................................................30
2-3-6 化合物 21 的合成 .........................................................................................31
2-3-7 化合物 22、24 的合成 .................................................................................32
2-4 銥金屬錯合物的合成...............................................................................................33
2-4-1 化合物 28 的合成 .........................................................................................34
2-4-2 化合物 29、30、31 的合成 .........................................................................34
2-4-3 化合物 34、35 的合成 ................................................................................35
2-5 釕金屬錯合物光物理性質測量...............................................................................36
2-6 銥金屬錯合物光物理性質測量...............................................................................40
2-7 結論...........................................................................................................................44
三、實驗部分..........................................................................................................................46
3-1 實驗儀器...................................................................................................................46
3-1-1 核磁共振光譜儀(nuclear magnetic resonance spectroscopy, NMR)............46
3-1-2 高解析質譜儀(mass spectrometry)...............................................................46
3-1-3 傅立葉轉換紅外光譜儀(Fourier transform infrared red spectrometer, FT-IR)
..................................................................................................................................46
3-1-4 紫外-可見光光譜儀(UV–Vis spectroscopy).................................................47
3-1-5 螢光光譜儀(flourescence spectroscopy).......................................................47
3-2 實驗藥品...................................................................................................................47
3-2-1 實驗藥品試劑 ...............................................................................................47
3-2-2 薄層色層分析(thin layer chromatography, TLC).........................................47
3-2-3 管柱色層分析(column chromatography)......................................................47
3-3 合成步驟與光譜資料...............................................................................................47
參考文獻..................................................................................................................................79
附錄一......................................................................................................................................89
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指導教授 謝俊結 吳國暉 審核日期 2023-8-16
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