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研究生： 黃子佳
Huang, Tzu-Chia
論文名稱： 利用新穎氮轉移試劑對胺基酸衍生物進行氮轉移反應探討之研究
Novel N-transfer Reagent for Converting α-Amino Acid Derivatives to α-Diazo Compounds
指導教授： 周鶴軒
Chou, Ho-Hsuan
學位類別： 碩士
Master
系所名稱： 理學院 - 化學系
Department of Chemistry
論文出版年： 2021
畢業學年度： 109
語文別： 中文
論文頁數： 164
中文關鍵詞： 氮轉移試劑 、胺基酸 、重氮化合物 、三氮烯
外文關鍵詞： N-transfer reagent, amino acid, diazo compound, triazene
相關次數： 點閱：102  下載：20 
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    • 本篇研究使用新穎氮轉移試劑將十九種人體必需胺基酸的酯類衍生物逕轉換為對應的重氮化合物，試圖為N-H不對稱插入反應合成D型胺基酸提供新的起始物合成方法。透過各個案例間的產率比較，以及對於反應機構的了解，從中可以知道其立體障礙會決定三氮烯中間產物的生成量，進而影響最終重氮化合物的產率。而為了使試劑的應用性提高，於本篇中也提出兩種提高三氮烯生成量的方法，分別以時間及使用量作為改變因素，皆可以針對不同的氨基酸提高產率，不僅能藉此證明氮轉移試劑的應用性，也能間接看出官能基耐受度及部分產物的穩定性。其他相關研究的揭示則為試劑最高合成量的數據，及相關胺基酸起始物的製作方法和流程。

    This research was dedicated to converting 19 essential amino acid derivatives to α-diazo compounds, which would provide a new diazo synthesizing protocol. With the deep insight into the mechanism and comparison between the cases, we could conclude that triazene intermediate dominated the yield of diazo. Besides, the formation of triazene would be affected by the hindrance on the α-position.
    To afford higher yield and demonstrate more application of this reagent, two methods were mentioned in this research. First, according to Le Chatelier principle, we could use more ammonium salt to enhance the formation of triazene, giving higher yields of diazo compounds. Also, we extended the time of 0℃ condition, ensuring that there is sufficient time for α-amine to react with the reagent before the reagent decomposed. Both of methods not only demonstrated the functional tolerance of N-transfer reaction to the side chain of the amino acids, but also afforded various kinds of diazo compounds in good yields. In addition, the related procedure for synthesizing ammonium salt were also presented in this research.

    摘要 I 誌謝 VIII 目錄 IX 圖目錄 XI 表目錄 XII 流程目錄 XIII 1. 前言 1 1.1 胺基酸 1 1.1.1 胺基酸合成方法-Strecker反應 1 1.1.2 D-型胺基酸及其應用 2 1.2 插入反應(Insertion reaction) 3 1.2.1 以N-H插入反應製備D-型胺基酸衍生物 3 1.3 重氮化合物 4 1.3.1 α-羰基重氮化合物 5 1.3.2 α-羰基重氮化合物合成 7 1.3.3 三氮烯裂解法 9 1.4 三氮烯及重氮鹽化合物 11 1.4.1 三氮烯化合物 11 1.4.2 重氮鹽化合物 12 1.5 研究動機 13 2. 結果與討論 15 2.1 實驗設計 15 2.2 疏水性側鍊(Hydrophobic Side Chain)氮轉移反應討論 17 2.2.1 銨鹽起始物合成 17 2.2.2 氮轉移反應初步討論 19 2.2.3 優化銨鹽起始物合成 21 2.2.4 疏水性側鍊胺基酸氮轉移反應討論 23 2.3 極性帶電荷側鍊(Polar charged Side Chain)氮轉移反應討論 27 2.3.1 起始物合成 27 2.3.2 氮轉移反應討論 28 2.3.3 組胺酸(Histidine)的氮轉移反應 30 2.4 極性不帶電荷側鍊(Polar Uncharged Side Chain)氮轉移反應討論 31 2.4.1 側鍊末端醯胺討論 31 2.4.2 側鍊末端乙醯胺討論 32 2.5 親核基團側鍊(Nucleophilic Side Chain)氮轉移反應討論 34 2.5.1 絲胺酸及息寧胺酸的氮轉移討論 35 2.5.2 半胱胺酸(Cysteine)的氮轉移反應討論 38 2.5.3 胱胺酸(Cystine)的氮轉移反應討論 39 2.6 氮轉移反應整體討論 42 2.6.1 異白胺酸對不同冰浴時間之氮轉移反應 44 2.6.2 一小時冰浴時間之氮轉移反應 44 3. 結論 47 4. 實驗部分 48 4.1 General Information 48 4.2 Concise Synthesis of the N-Transfer Reagent D7 49 4.3 Synthesis Procedure for Ammonium Salt 52 4.3.1 Synthesis Procedure for Hydrophobic-OBn 52 4.3.2 Synthesis Procedure for Hydrophobic-OCH2Bn 54 4.3.3 Synthesis Procedure for Tyr-OMe 58 4.3.4 Synthesis Procedure for polar charged side chain 59 4.3.5 Synthesis Procedure for His-OMe Salt 62 4.3.6 Synthesis Procedure for polar uncharged side chain 63 4.3.7 Synthesis Procedure for Nucleophilic side chain 67 4.4 Synthesis procedure for Diazo 74 5. 參考文獻 92 6. 核磁共振光譜 95 7. 附錄 156

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