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Title: | 以反應性定量建立醣鏈結反應及其中間產物之演算法 Establishment of an Algorithm for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity |
Authors: | Chun-Wei Chang 張峻瑋 |
Advisor: | 王正中 |
Co-Advisor: | 吳世雄 |
Keyword: | 立體選擇,醣鏈結反應,反應機構探討探, Glycosylation, |
Publication Year : | 2019 |
Degree: | 博士 |
Abstract: | 在化學合成醣類衍生物時,立體選擇性、位向選擇性以及產率皆為醣鏈結反應中重要的環節,然而,儘管在這數十年來許多文獻已記載了許多可能的解決方向,這些合成上的困境依然無法有效解決。在本論文中,我們首度發現立體選擇性醣鏈結可以利用醣予體的活性進行快速預測,而反應機構的探討更結論出醣基碘化物以及醣基三氟甲磺酸化物這兩種截然不同的中間產物主導著整個醣鏈結反應,雖然不同比例的醣基中間體劇烈的影響反應之選擇性,本論文已有效的歸納和整合其分子行為。除此之外,透過相對反應數值以及統計上的分析,我們首次量化醇類分子在酸性條件下的活性,並且有效的定義出醣鏈結反應之趨勢和高產率區間。最後,我們成功建構出一個數學方程式來預測醣鏈結反應之結果,此方程式涵蓋眾多重要的變因,包括不同活性的醣予體、醣受體、溶劑、離去基、以及啟動子。此預測系統不但具備了高準確性,也可幫助我們在簡潔的步驟中高效地合成出一系列的醣類衍生物。 Stereoselectivity, regioselectivity and reaction yield are paramount for successful glycosylation reactions, which are key to the chemical synthesis of glycoconjugates. However, achieving them has remained a major challenge for many decades despite the significant efforts documented in the literature. To rationalize our discovery, in this thesis, we have discovered that the stereoselective outcome can be predicted by sugar reactivity with a defined relative reactivity value (RRV). Our mechanism studies also concluded that reaction was dominated by two distinct intermediates, glycosyl triflate and glycosyl iodide. The relative quantities of glycosyl triflate to iodide greatly influence the stereoselectivity, and glycosyl intermediate’s behavior was clarified in this work. The RRV of acceptors (ARRV) is designed to indicate the reactivity of an alcohol under acidic condition for the first time. A trend for the yields and a guideline for high-yielding reactions can also be defined based on RRV-ARRV, using a statistical approach. The equation has involved numerous crucial factors, such as donor and acceptor reactivity, solvent polarity, the leaving group and the promotor. Many carbohydrate-based derivatives can be efficiently synthesized in concise steps with high accuracy. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74819 |
DOI: | 10.6342/NTU201904294 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 化學系 |
Files in This Item:
File | Size | Format | |
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ntu-108-1.pdf Restricted Access | 24.73 MB | Adobe PDF |
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