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研究生: 林琮鈞
Lin, Tsung-juin
論文名稱: 探討1,6-脫水葡萄糖的位置選擇性和醣鍵結反應
Regioselective protection of 1,6–anhydro–glucopyranoside and its glycosylation reaction
指導教授: 王正中
Wang, Cheng-Chung
杜玲嫻
Tu, Ling-Hsien
口試委員: 王正中
Wang, Cheng-Chung
杜玲嫻
Tu, Ling-Hsien
羅順原
Luo, Shun-Yuan
口試日期: 2023/01/11
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2023
畢業學年度: 111
語文別: 中文
論文頁數: 73
中文關鍵詞: 醣基化反應脫水醣
英文關鍵詞: glycosylation, anhydro sugar
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202300298
論文種類: 學術論文
相關次數: 點閱:62下載:0
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  • 醣化學為有機化學領域中重要的部分,不同的醣體會在生物表面上有不同的表現或是機制,深入了解醣在細胞表面扮演的角色有助於藥物發展以及疫苗開發。由於醣反應的特殊性以及結構的複雜性,這讓醣化學的發展受到阻礙。由於醣合成免不了繁雜的保護以及去保護過程因此本篇論文將討論具發展潛力的構建原件1,6-脫水-D-β-葡萄醣,1,6-脫水-D-β-葡萄醣上結構具有特殊的分子內自保護的鍵橋可以減少保護與去保護過程,加上不同於一般4C1醣體的1C4的構型,脫水醣上鍵橋對C3羥基造成立體結構使我們可以選擇性在C4上苄基和C2乙醯丙酸基保護。1,6-脫水-D-β-葡萄醣特殊的開環機制,提供了更多醣體在C1修飾的選擇,如接上疊氮後可以進行點擊化學反應等。最後修飾過後的1,6-脫水-D-β-葡萄醣能藉由立體構型選擇性與苷露醣予體進行 (1→3) 醣基化反應,而且C2、C4上不同的保護基也可以透過專一性去保護後得到的羥基進行 (1→2) 或 (1→4) 的選擇性醣基化反應,大幅增加醣基化反應路徑的多樣性。

    Several glycans are prevalent at the surface of cells manifesting variety of functions making them to be targets of drug and vaccine development. To understand the mechanism of their functions, glycans of interest must be accessible in the required structural form and adequate quantity for biological assessments. To this end, chemical synthesis is one of the tools employed to access glycans. Due to structural complexity and diversity of glycans, their chemical synthesis needs a series of protection-deprotection procedures. Herein, we report the use of 1,6-anhydroglucose unit which consists of a special intramolecular self-protection bridge aimed at reducing the protectiondeprotection steps during glycan synthesis. Structurally, the 1,6-anhydro-D-β-glucoside has a 1C4 conformation which is different from the general 4C1 conformation of sugars. As the anhydro bridge creates a three-dimensional hindrance for the C3 OH group, the remaining two hydroxyl groups can be selectively modified with orthogonal protecting groups. In this case, while the C4 OH group was selectively benzylated, the C2 OH group was subjected to levulinoylaton. Then, the resulting 1,6-anhydro-D-β-glucoside can undergo (1→3) glycosylation reaction through the free C3 OH group with variety of glycoside donors to build disaccharides. Moreover, the orthogonal protecting groups at C2 and C4 can also be selectively removed to be used for (1→2) or (1→4) selective glycosylation which greatly increases the diversity of glycosylation reaction pathways.

    謝誌 i 中文摘要 iii Abstract iv 目錄 v 圖目錄 vii 表目錄 viii 流程目錄 ix 縮寫表 x 第一章 緒論 1 一、引言 1 (一) 碳水化合物的結構 (the structure of carbohydrate) 2 (二) 單醣的結構 3 (三) 單醣的立體組態 (configuration) 4 二、醣合成 5 (一) 醣基化反應 (glycosylation reaction) 6 (二) 醣基化合成挑戰 7 三、影響立體和位置選擇性的因素 8 (一) 變旋異構效應 (anomeric effect) 8 1. 超共軛效應 (hyperconjugation) 8 2. 偶極–偶極相互作用 (dipole–dipole interaction) 9 (二) 鄰近基效應 (Neighboringgroup participation, NGP) 9 (三) 遠程參與效應 (Longrange participation, LRP) 10 (四) 溶劑效應 10 (五) 位置選擇性 11 1. 選擇性修飾變旋異構中心 12 2. 選擇性羥基保護 12 3. 雙羥基參與的選擇性保護 13 四、1,6-脫水醣 (1,6-anhydro sugar) 16 (一) 1,6-脫水醣合成 18 1. 路徑a: C1離去基鹼性下合成脫水醣 20 2. 路徑b: C1離去基酸性下合成脫水醣 21 3. 路徑c: C6離去基鹼性下合成脫水醣 22 4. 路徑d: 分子內費里爾重排合成脫水醣 23 5. 路徑e: 親電基團活化合成脫水醣 24 (二) 1,6-脫水吡喃醣 (1,6-anhydropyranose) 應用 25 1. O–親核基開環 25 2. S–親核基開環 26 3. N–親核基開環 26 4. 鹵素親核基開環 27 (三) 1,6-脫水醣選擇性保護 28 五、醣基化反應的預測 30 (一) 武裝和非武裝醣 (armed and disarmed saccharides) 30 (二) 相對反應性數值 (Relative Reactivity Value, RRV) 31 (三) 親核性反應數值 (Acceptor nucleophilicity constant, Aka) 33 (四) RRV/Aka 數值 (RRV/Aka ratio) 34 六、研究動機 37 第二章 結果與討論 38 一、1,6-脫水葡萄醣合成 38 二、1,6-脫水葡萄吡喃糖選擇性討論 43 (一)、1,6-脫水-D-β-葡萄吡喃醣上羥基選擇性 43 (二)、1,6-脫水-4-O-苄基-D-β-葡萄吡喃醣醣基化反應 46 (三)、1,6-脫水-4-O-苄基-D-β-葡萄吡喃醣上羥基選擇性保護與結構分析 46 (四)、1,6-脫水-4-O-苄基-D-β-葡萄吡喃醣醣基化反應討論 51 第三章 結論 54 第四章 參考資料 55 第五章 實驗方法與光譜 61 General Information 61 General procedure for Aka experiment of acceptors 62 參考資料 72 1H and 13C NMR spectra for compounds 73

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