探討遠端參與效應於苯甲醯基與其衍生物於葡萄硫苷醣予體之醣鍵結反應

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許姿琳(Zi-Lin Hsu) 查詢紙本館藏

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化學學系

論文名稱

探討遠端參與效應於苯甲醯基與其衍生物於葡萄硫苷醣予體之醣鍵結反應
(Study of Remote Participation Effect of Benzoyl Group and its Derivatives by Using Thioglucoside Donors in Glycosylation)

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至系統瀏覽論文 (2029-5-22以後開放)

摘要(中)

醣鍵結反應一直在醣化學當中位居重要的地位，化學家多年來致力於發展出可以有效製備多醣的方法。而如今如何合成出純度好、產率高且能夠有效控制其產物立體選擇性的策略是正在面臨的困境。
近年來，有許多研究團隊發現，當 C-3、C-4、C-6 上利用酯基基團保護時能得到大量特定的立體選擇性產物，其中透過應用於特定醣體之位向上，可以得到傾向生成 1,2-順式醣苷鍵的結果。經過研究顯示認為是因遠端參與效應而得此結果，但由於遠端參與效應如何去影響反應的生成以及對於反應的影響程度不明確，許多研究團隊利用光譜學、理論計算與實驗操作等方法，試圖釐清遠端參與效應的發生與成果卻仍存在著爭議，無法對遠端參與效應有統一的論述，也因此無法廣泛利用遠端參與效應於合成多醣上。
而在本文研究當中先選用 C-3、C-4、C-6 上利用苯甲醯基保護之葡萄糖醣予體進行醣鍵結反應，並將其實驗結果帶入本實驗室建立的預測性模型，以系統性分析的角度觀察醣鍵結反應後產物之立體選擇性，實驗流程概括四個部分，製備苯甲醯基與其衍生物之葡萄糖醣予體以及葡萄糖醣受體、測量醣予體之反應性 (RRV) 與受體之反應性 (Aka)、進行醣鍵結反應、將其結果帶入模型分析。
且通過與本實驗室先前的例子，C-3、C-4、C-6 上分別以乙醯基基團保護的葡萄糖醣予體與不同型態之葡萄糖醣受體和甲醇進行醣鍵結反應的結果進行比較。鑒於先前的研究只針對葡萄糖醣受體與甲醇作為受體反應，因此在本文實驗中選用更多不同型態的受體進行醣鍵結反應，期望能更加全面的探討受體帶來的影響外，更加以透過於 C-6 上保護使用苯甲醯基衍生物之葡萄糖醣予體進行醣鍵結反應，以利用不同位置進行保護以及使用不同保護基團的角度，探討遠端參與效應於反應中對產物之立體選擇性的影響以及其影響程度。

摘要(英)

In the realm of glycoscience, the synthesis of polysaccharides stands as a critical endeavor, necessitating the attainment of high purity, optimal yield, and precise stereoselectivity. While the construction protocols of 1,2-trans linkages rely on neighboring group effect, there is no straightforward solution for the formation of 1,2-cis glycosidic bonds.
Recent investigations have underscored the strategic introduction of C-3, C-4, C-6 ester groups on various glycosyl donors as a way to facilitate the formation of 1,2-cis glycosidic linkages, attributed to the remote participation. However, the elucidation of the mechanism and impact of the remote participation remains enigmatic, prompting dispute within the scientific community. Employing an array of analytical techniques including NMR (Nuclear Magnetic Resonance), IR (Infrared Spectroscopy), and theoretical calculations researcher have strived to unravel the intricacies of remote participation, yet consensus remains elusive, impeding its practical application in polysaccharide synthesis.
In this study, we present our investigation into the utilization of benzoyl group-modified glucosyl donors in glycosylation reactions with various acceptors, leveraging a predictive model developed in our laboratory to analyze stereoselectivity. Through meticulous experimentation, we assessed the occurrence of remote participation and compared the outcomes with those obtained using glucosyl donors bearing acetyl groups at corresponding positions.
Furthermore, we scrutinized the impact of benzoyl group derivatives in the glycosylation processes, enriching our understanding the role of remote participation.
Our workflow encompassed the synthesis of glucose acceptors and donors bearing benzoyl group substituents, carried out glycosylation reactions, a systematic evaluation of stereoselectivity and remote participation effect. The findings underscore the potential of remote participation in directing glycosylation outcomes and shed light on the modulatory influence of benzoyl group substituents on glycosylation stereochemistry.

關鍵字(中)

★ 醣鍵結反應
★ 立體選擇性
★ 鄰基效應
★ 遠端參與效應

關鍵字(英)

★ glycosylation
★ stereoselectivity
★ neighbor group effect
★ remote participation

論文目次

摘要 ............................................................................................................................................. i
Abstract ....................................................................................................................................... ii
誌謝辭 ....................................................................................................................................... iii
目錄 ............................................................................................................................................ v
圖目錄 ...................................................................................................................................... vii
表目錄 ....................................................................................................................................... ix
流程目錄 .................................................................................................................................... x
縮寫表 ....................................................................................................................................... xi
第一章緒論 ........................................................................................................................ 1
1.1 引言 ................................................................................................................................ 1
1.2 醣類的合成方法 ............................................................................................................ 3
1.3 醣類之結構判別與立體化學 ........................................................................................ 4
1.4 醣鍵結反應 .................................................................................................................... 6
1.5 影響醣鍵結立體選擇性之反應機制探討 .................................................................... 6
1.6 影響醣鍵結反應之立體選擇性的因素 ........................................................................ 9
1.6.1 常在性因素 (Permanent factors)............................................................................... 9
1.6.1.1 相對反應值 (Relative Reaction Value, RRV) .................................................. 9
1.6.1.2 受體親核常數 (Acceptor Nucleophilic Constant, Aka) ................................. 11
1.6.1.3 變旋異構效應 (Anomeric effect) .................................................................... 12
1.6.1.4 鄰基效應 (Neighboring group effect) ............................................................. 13
1.6.1.5 遠端參與效應 (Remote participation effect) .................................................. 14
1.6.2 環境性因素 (Environmental factors) ...................................................................... 15
1.6.2.1 溫度效應 (Temperature effect) ....................................................................... 15
1.6.2.2 促進劑效應 (Promoter effect) ......................................................................... 16
vi
1.6.2.3 溶劑效應 (Solvent effect) ............................................................................... 18
1.7 文獻回顧 ...................................................................................................................... 19
1.7.1 利用醣予體之相對反應性與受體親核常數分析醣鍵結反應 .............................. 19
1.7.2 醣鍵結反應取得 1,2-順式醣苷鍵之方法 .............................................................. 22
1.7.3 遠端參與效應之爭論 .............................................................................................. 24
1.8 研究動機 ...................................................................................................................... 33
第二章結果與討論 .......................................................................................................... 34
2.1 葡萄硫苷醣予體之合成 .............................................................................................. 34
2.2 醣受體之合成 .............................................................................................................. 37
2.3 醣予體相對反應性 (RRV) 之測量 ........................................................................... 39
2.4 受體親核常數 (Aka) 之測量 ..................................................................................... 40
2.5 醣鍵結反應之立體選擇性結果 .................................................................................. 40
2.6 系統性分析立體選擇性之結果 .................................................................................. 45
第三章結論 ...................................................................................................................... 68
第四章實驗流程以及光譜數據 ...................................................................................... 69
4.1 General procedure......................................................................................................... 69
4.2 Synthesis of glucosyl donor .......................................................................................... 70
4.3 Synthesis of glucosyl acceptor ..................................................................................... 80
4.4 General procedure for RRV experiment of thioglycosides 24, 26................................... 86
4.5 General procedure for Aka experiment of acceptors 24 ................................................ 88
第五章參考資料 ............................................................................................................ 167
附錄-光譜 ............................................................................................................................... 171

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指導教授

王正中侯敦仁(Cheng-Chung Wang Duen-Ren Hou)

審核日期

2024-6-24

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