The thesis described the development of a solid-phase synthetic method for the synthesis of α(2→9) oligosialic acids. The TentaGel was chosen as the solid support and Wang linker was used to link with sialic acid. The use of 5-N,4-O-carbonyl protected thiosialoside as donor provided an excellent α selectivity on solid phase sialylation reaction. To achieve the synthesis of higher order oligosialic acids, a semiautomatic reaction system was used to keep the resin away form moisture. To increment the yield of sialylation reaction, sialyl phosphate donor and acetylation step to protect remained hydroxyl groups after sialylation was tested.

本篇論文之目的在於發展出利用固相合成的方法合成出α(2→9)唾液酸寡
糖，藉由Wang type TentaGel 作為固相材料，使用5-N,4-O-羰基保護的唾液酸
作為予體，可成功的獲得高度α 選擇性的α(2→9)唾液酸鍵結。為了得到更長單
元的α(2→9)唾液酸寡糖，密閉系統的設計用以隔絕空氣中水氣的干擾，使用新
發展的磷酸唾液酸予體以期增加反應性、以及在合成過程中反保護未反應之羥
基等方式皆被嘗試運用。

Table of Contents i
Index of Schemes iv
Index of Figures vii
Index of Tables viii
Abbreviations ix
Abstract xi
中文摘要 xii

Chapter 1. Introduction 1
1 Solid-phase Synthesis of Oligosaccharide 1
1-1 Central Aspects of Solid-phase Oligosaccharide Synthesis 2
1-2 Polymer Solid Supports 3
1-3 Linker Systems 7
1-3-1 Linker Types. 8
1-3-2 Cleavages of Linkers 10
1-3-2-1 Acid-labile Linkers 10
1-3-2-2 Base Labile Linkers 13
1-3-2-3 Silyl Ether Linkers 15
1-3-2-4 Thioglycoside Linkers 16
1-3-2-5 Linker Cleaved by Oxidation 17
1-3-2-6 Linkers Cleaved by Hydrogenation 17
1-3-2-7 Linkers Cleaved by Olefin Metathesis 19
1-4 On-support Monitoring 21
1-4-1 Colorimetric Methods 22
1-4-2 Spectroscopy 24
2 Polysialic Acids 25
3 O-Sialylation 27
3-1 Inherent Problems of O-sialylation 27
3-2 Leaving Groups of Sialyl Donors. 29
3-3 Auxiliaries of Sialyl Donors 32
3-4 C-5 Modifications of Sialyl Donors 33
3-5 Synthesis of Oligosialic acids 35
4 Glycosyl Phosphate Donors 37
5 Specific Aim and Concepts of Synthetic Design 42
Chapter 2. Result and Discussion 44
1 Synthesis of Thiosialoside Donor 44
2 Synthesis of Disialic Acid in Solution Phase 46
3 Immobilization of Sialic Acid 51
4 Chain Elongation 58
5 Design of Closed System 65
6 Synthesis of Sialyl Phosphate Donor 68
7 Glycosyl Phosphate Donor and O-TMS Acceptor System 72
8 Aceylation 74
Chapter 3. Conclusions 77
Chapter 4. Experimental Section 78
1 General Procedures 78
1-1 Reagents and Solvents 78
1-2 Spectra Notes 78
2 Procedures and Spectroscopy Data 79

References 103
Appendix 121
Index of Appendix 123

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