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研究生:蔡文璋
研究生(外文):Wen-Chang Tsai
論文名稱:有機溶劑中以脂肪分解酵素為觸媒進行(α)-苯基乙胺之轉胺化分割
論文名稱(外文):Enzymatic Resolution of (α)-Phenylethylamine Using Candida antarctica Lipase-B with Organic Solvent
指導教授:蔡少偉蔡少偉引用關係
指導教授(外文):Shau-Wei Tsai
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學工程學系碩博士班
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:67
中文關鍵詞:消旋亞胺動力分割(α)-苯基乙胺
外文關鍵詞:(α)-phenylethylaminekinetic resolutionimineracemization
相關次數:
  • 被引用被引用:1
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  • 下載下載:10
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  本研究動機在於開發酵素動態動力分割製程,自外消旋胺獲得其高純度鏡像異構醯胺。在研究方向上分成兩大部分,其一為以(S)-(α)-苯基乙胺及苯乙酮為反應基質,合成(S)-亞胺,並探討有機鹼觸媒、反應物濃度、有機溶劑種類及反應溫度等操作變因對消旋反應之影響。初步實驗結果顯示並未獲得外消旋亞胺。另一部分則以外消旋(α)-苯基乙胺為反應基質,進行酯類的篩選以及探討溫度、反應物濃度和有機溶劑對酵素選擇性之影響。實驗發現在100℃以下之正癸烷中,以甲氧基乙酸乙酯與外消旋(α)-苯基乙胺進行酵素動力分割反應,可獲得較佳的鏡像比值(E = 21.1);以5 mM外消旋 (α)-苯基乙胺與10 mM甲氧基乙酸乙酯進行酵素動力分割,發現當溫度在70~80℃時,酵素有最佳之選擇性(E > 100)。
  This research is aimed to develop an enzymatic dynamic kinetic resolution process, in which racemic (α)-arylamine is the substrate and a highly stereo-pure amide is obtained by employing an enzymatic amination coupled with in situ racemization of the remaining (S)-amine. The main works include racemization of (S)-(α)-phenylethylamine and enzymatic kinetic resolution of (R,S)-(α)-phenylethylamine. For the former, we synthesized and purified the (S)-imine synthesized from (S)-(α)-phenylethylamine and acetophone. Then, effects of the operation parameters such as organic bases as catalysts, reactant concentration, solvents and temperature were studied. Unfortunately, no 1, 3-proton shift reaction for the (S)-imine occurred. For the latter, the kinetic resolution of racemic (α)-phenylethylamine were investigated, in which esters, temperature, amine and ester concentrations were varied. The results indicate that with racemic (α)-phenylethylamine and ethyl methoxyacetate as substrates, high lipase enantioselectivity ( E > 100) was obtained at the temperature range of 70~80℃ in decane.
總 目 錄
中文摘要………………………………Ⅰ
英文摘要………………………………Ⅱ
目錄……………………………………Ⅲ
圖目錄…………………………………Ⅵ
表目錄…………………………………Ⅷ

內 文 目 錄
第一章 緒論及文獻回顧.........................1
1.1 前言......................................1
1.2 對掌性異異構..............................1
1.3 動態動力分割..............................2
1.4 單一鏡像異構胺之製造途徑..................4
1.4.1 非鏡像異構物結晶法......................4
1.4.2 非對稱合成鏡像異構胺....................5
1.4.2.1 亞胺製備..............................5
1.4.2.2 亞胺的選擇性加氫反應..................6
1.4.3 利用脂肪分解酵素進行光學胺之分割反應....7
1.5 單一鏡像異構胺的消旋......................9
1.5.1 鏡像異構胺之消旋........................9
1.5.2 經由亞胺進行鏡像異構胺之消旋............9
1.5.2.1 亞胺異構化............................11
1.5.2.2 亞胺與一級胺反應......................11
1.6 Candida Antarctic lipase-B (CALB)簡介...13
1.6.1 脂肪分解酵素............................13
1.6.2 CALB來源及特性..........................14
1.6.3 CALB的三級結構及性質....................14
1.6.4 CALB之熱穩定性..........................15
1.6.5 溶劑對CALB的影響........................16
1.7 研究動機..................................18

第二章 實驗...................................20
2.1 實驗藥品暨設備............................20
2.1.1 實驗藥品................................20
2.1.2 實驗設備................................21
2.2 分析方法..................................22
2.2.1 1-phenyl-N-(1-phenylethylidene)ethanamine與苯乙酮之分析條件.............................22
2.2.2 (R,S)-(α)-苯基乙胺之分析條件…..........25
2.3 實驗方法..................................26
2.3.1 製備亞胺1-phenyl-N-(1-phenylethylidene)ethanamine.....................................26
2.3.1.1 製備方法一............................26
2.3.1.2 製備方法二............................26
2.3.2 製備內標準物亞胺(R,S)-N-(4-methoxybenzylidene)-1-phenyl-ethanamine........27
2.3.3 合成異丁醇鉀............................27
2.3.4 (S)-亞胺之消旋..........................28
2.3.4.1 低溫下(S)-亞胺之消旋測試..............28
2.3.4.2 高溫下(S)-亞胺之消旋測試..............28
2.3.5 酵素之光學分割..........................28
2.3.5.1 溫度對酵素分割反應之影響..............28
2.3.5.2 胺濃度對酵素反應速率之影響............29
2.3.5.3 甲氧基乙酸乙酯濃度對酵素反應速率之影響29
2.3.5.4 不同酯類對酵素分割之選擇性影響........30
2.3.5.5 加入叔戊醇對酵素分割之影響............30
2.3.5.6 自發性轉胺化反應之影響................31

第三章 結果與討論.............................32
3-1 亞胺(1-phenyl-N-(1-phenylethylidene)ethanamine)之合成與純化.......................32
3-2 鹼觸媒進行亞胺消旋反應....................32
3-3 酯類篩選..................................38
3-4 高溫下酵素進行轉胺化反應之探討............40
3-5 溫度變化對酵素選擇性及反應速率之影響......44
3-6 酯類濃度變化對反應速率和選擇性的影響......46
3-7 胺濃度變化對反應速率和選擇性的影響........47
3-8 溶劑對酵素反應之影響......................48

第四章 結論暨未來展望.........................51
參考文獻.......................................53
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