臺灣博碩士論文加值系統

本論文分為兩大部分:
1. 在建構 beta-選擇性醣&;#33527;鍵策略中，溶劑參與效應一鍋化醣質化反應 (SPOG) 已被普遍使用在低濃度&;#33096;類混和溶劑反應系統中。這種策略可在一鍋化策略的情況下控制生成良好的 立體選擇性。同時，我們更衍生應用於正交醣基化反應策略，將醣基磷酸酯予體及硫醣受體搭配，經由一鍋化的方式合成產率極佳的寡醣分子。

2. 葡萄糖胺是一種和人類息息相關重要醣分子之一，一般含有胺基或是乙醯基保護的胺基。而三疊氮 (azido，N3) 保護基可在溫和的情況下被還原去保護，並且因為三疊氮保護基缺乏鄰助基效應一般常被用來使用製備beta 醣&;#33527;鍵。我們發展了具備高產率及良好的1,2-反式 beta-選擇性的溶劑鄰助基策略，使用在2-三疊氮-去氧葡萄糖胺予體上，並且成功的得到與生物有關的F1-apha前驅物以及(1,6)-beta葡萄糖胺寡醣鏈。

This thesis is divide into two parts:

1. Solvent participating one-pot glycosylation (SPOG) strategy was developed on the base of low concentration beta-selective glycosylation method. This strategy enables the control of stereochemistry in one-pot glycosylations through solvent addition. Meanwhile, further application of the low concentratnion glycosylation (LCG) to orthogonal glycosylation strategy is explored. Combining glycosyl phosphates and thioglycosides, oligosaccharides could be synthesized in a one-pot manner to furnish in good yield and excellent stereoselectivity.

2. Glucosamine is one of the major amino sugars present in human-related oligosaccharides, which contain an amino group (or acetamido) at the C-2 position. The azido function can readily be reduced to amine under mild conditions. Due to the non-participation nature, 2-azido-2-deoxy glycosyl donors are mandatory substrates for construction of 1,2-cis apha-glycosidic bond under specific reaction condition We developed a high-yielding and stereocontolled construction of 1,2-trans-beta-glycosidic linkages with 2-azido-2- deoxy glycopyranosyl donors using the solvent participated one-pot glycosylation strategy. We successfully prepared some biological relevant oligosaccharide targets such as F1-apha precursor trisaccharide, and beta-(1,6) glucosamine.

目錄
簡寫表 iii
目錄 v
圖目錄 ix
流程目錄 xi
表目錄 xii
第一章 溶劑參與效應醣基化反應一鍋化策略 1
一.緒論 1
1.1 醣化反應 1
1.2 鄰基效應 (neighboring group participating，NGP) 之 ??選擇性位向控制 1
1.2.1 C-2 羰基鄰助基效應 2
1.2.2 C-2異原子之鄰助基效應 3
1.2.3 總結 4
1.3 腈類溶劑效應控制立體選擇性 4
1.3.1 腈類溶劑與乙醚溶劑之比較 7
1.3.2 其它離去基 9
1.4一鍋化寡醣合成策略 10
1.4.1 正交醣基化反應策略 11
1.4.2 化學選擇醣基化反應策略 13
1.4.3前置活化(pre-activation)醣基化策略 16
1.5 實驗動機 17
二.結果與討論 18
2.1合成策略 18
2.2 醣基化(glycosylation)反應測試 20
2.2.1 葡萄醣予體醣基化反應測試 20
2.2.2 醣基磷酸酯予體(glycosyl phosphate donor)測試 22
2.2.3 正交醣基化反應 (Orthogonal glycosylation) 測試 24
2.3 正交醣化反應(Orthogonal glycosylation)之應用 27
2.3.1 連續串聯式(sequential glycosylation)合成策略 27
2.3.2 一鍋化醣基化反應(one-pot glycosylation) 30
2.4 結論 32
第二章 2-疊氮-2去氧醣予體合成天然寡醣 33
一.緒論 33
1.1 葡萄糖胺複合醣體及天然物 33
1.2 一般製備去氧糖胺 ??醣鏈的方法 36
1.2.1 Koenigs-Knorr 反應 36
1.2.2 利用唑啉環類 (Oxazoline) 生產1,2-反式 ??醣苷鍵 37
1.2.3 利用N-苯二甲醯亞氨基 (phthalimido)鍵結 ??n醣苷鍵 40
1.3 利用鍵三氯乙氧基醯基 (2-2-2-trichloroethoxycarbonyl，Troc ) 鍵結 ??n醣苷鍵 41
1.4 2-三疊氮-2-去氧醣予體 (2-azido-2deoxy donors) 醣基化反應 42
1.4.1 製備2-疊氮-2-去氧醣予體 (2-azido-2deoxy donors) 43
1.4.2 2-疊氮-2-去氧醣予體 (2-azido-2deoxy donors) 醣基化反應 45
1.4.2.1 鹵素離去基 45
1.4.2.2 三氯醯胺酯 (trichloroacetimidate) 離去基 46
1.4.2.3 硫醣予體 (thioglycoside) 48
1.4.2.4 醣基磷酸酯 (phosphate glycoside) 48
1.4.3 疊氮保護基去保護方法 49
1.5 結論與本研究之動機目的 50
二.結果與討論 53
2.1實驗設計 53
2.2 單醣起使物 (monosaccharide building block) 的製備: 54
2.2.1 2-三疊氮-2-去氧醣予體(2-azido-2-deoxy glycosyl donors)基礎材料製備 54
2.2.2葡萄糖胺醣受體之製備 (Preparation of 2-azido-2-deoxy glycosyl accpetor) 57
2.3 2-三疊氮-2-去氧葡萄糖胺予體之醣基化反應檢驗 60
2.4 N3取代基的拉電子效應(disarming): 64
2.5 葡萄糖胺一鍋化合成應用: 67
2.6結論 71
第三章 實驗部分 73
第四章、參考文獻 110
附錄 118
 

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