對甲苯磺酸在醣化學的應用：一個較環保的醣基建構單元合成法

中文摘要本論文旨在探討醣分子的相關合成，內容分為三個部份：第一章. 利用對甲苯磺酸 (TsOH) 作為催化劑以修飾天然醣分子為醣基建構單元。首先探討非胺基糖與糖胺分子的全乙醯化反應。以催化量的TsOH、近當量的醋酸酐、與不使用或極少量溶劑下得到極佳的反應效率，並利用反應溫度消除五員環產物的發生。接著再以TsOH催化劑建立了一鍋化全乙醯化-硫醇化與一鍋化縮醛化-乙醯化的合成方法，簡化醣基建構單元的合成。第二章. 我們嘗試探討醣基化反應濃度效應，並開發了實用的低濃度醣基化反應方法以建立1,2-反式 -醣鍵。(此方法)在多種醣予體與醣受體的搭配測試中均得到很好的選擇性與產率；並被應用於三個寡醣分子：(1→6)glucan、Gb3、與 isoGb3的合成上。接著我們進行計量變化實驗、變溫核磁共振實驗與反應中間體的補捉實驗，嘗試重新探討低濃度類溶劑系統的醣基化反應非傳統性的機構。第三章. 將低濃度醣基化反應延伸應用於正交醣基化反應策略與反應活性基礎之化學選擇性醣基化反應策略。在正交醣基化反應中以醣基磷酸酯為醣予體，與硫糖分子進行一鍋二步醣基化反應，並順利得到三醣分子。在活性基礎醣基化反應中則以硫糖分子進行一鍋二步醣基化反應，得到三醣分子。

關鍵字

醣基建構單元；低濃度；醣基化反應

並列摘要

Abstract The dissertation is discussed about the synthesis methods of carbohydrates. There are three parts in the thesis: Chapter 1: p-Tolyl sulfonic acid (TsOH) is used as acid catalyst to modify the natural carbohydrate substrates into glycosyl building blocks. We first probe in the peracetylation of both non-amino sugars and amino sugars. The peracetylation is carried out in good or excellent yield with catalytic amount of TsOH, near stoichioment amount of acetic anhydride, and minimum solvent. Moreover, the accompanying furanoside product in peracetylation is suppressed by lower reaction temperature condition. We then apply TsOH-catalyzed acetylation to establish the one-pot acetylation-thioglycosidation and one-pot acetalation-acetylation to accelerate the sugar unit modification. Chapter 2: The second part in the thesis explores concentration effect in glycosylation, and then develop a practical low concentration glycosylation method (LCG) for construct 1,2-trans -glycosidic bond. Several glycosyl donors and acceptors are tested to give high stereoselectivity and good yield. The useful condition is then applied to synthesis three oligosaccharides: (1→6)glucan, Gb3, and isoGb3 in excellent yield. Besides, with the results of the experiments in changing amount of reaction component, observation in VT-NMR study, and intermediate trapping experiment encourage us to hypothesis the plausible mechanism of glycosylation in the mixed nitrile solvent system. Chapter 3: The low concentration condition is applied for two important oligosaccharides synthesis strategies: orthogonal glycosylation strategy, and reactivity-based chemo-selective glycosylation strategy. After testing with several glycosyl blocks, glycosyl phosphate is chosen as glycosyl donor to demonstrate the orthogonal glycosylation strategy with thioglycoside glycosyl acceptor. Consequently, desired trisaccharide is obtained under one-pot two-steps process. On the other hand, we use thioglycosides to grope for the feasibility of reactivity-based glycosylation strategy in low concentration glycosylation. As a preliminary result, expected trisaccharide product is carried out under one-pot two-steps manner.

並列關鍵字

glycosyl building block ； low-concentration ； glycosylation

參考文獻

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23. For pyranosyl acetate: (a) Ong, G. T.; Chang, K. Y.; Wu; S. H.; Wang, K. T. Carbohydr. Res. 1994, 265, 311318. (b) Tai, C. A.; Kulkarni, S. S.; Hung, S.-C.J. Org. Chem. 2003, 68, 87198722. For furanosyl acetate: (c) Ferrieres, V.; Geln M.; Boulch R.; Toupet, L.; Plusquellec, D. Carbohydr. Res. 1998, 314, 7983.

51. (a) Hashimoto, S.-i.; Honda, T.; Ikegami, S., J. C. S. Chem. Commun. 1989, 685687; (b) Tsuda, T.; Nakamura, S.; Hashimoto, S. Tetrahedron Lett. 2003, 44, 64536457; (c) Tsuda, T.; Nakamura, S.; Hashimoto, S.; Tetrahedron 2004, 60, 1071110737. phosphate MeCN

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對甲苯磺酸在醣化學的應用：一個較環保的醣基建構單元合成法

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