神經節苷脂在生物體中扮演許多的角色，如細胞辨識、細胞-細胞間的交互作用、細胞分化及細胞的訊息傳遞等。而從棘皮動物中分離出的新型神經節苷脂，在神經生長因子的輔助下，則可刺激大鼠 PC-12 細胞，增加神經再生的活性，為治療帕金森氏症等神經系統疾病的潛力藥物，文獻報導中指出，非還原端之唾液酸在 C-8 修飾有甲基及硫酸根的神經節苷脂其刺激神經再生活性更好。
本論文以有機合成的方法將唾液酸 C-8 修飾為甲基及硫酸根，但在進行 O-甲基化時，面臨唾液酸 C-5 之 N-甲基化之競爭反應，合成策略改為將 NHAc 轉換為疊氮基（N3）進行唾液酸 C-8 甲基化反應後，再還原疊氮基為胺基來進行醯胺鍵生成反應，完成唾液酸 C-8 甲基化且 C-5 分別修飾為 NHAc 及 NHGc 的唾液酸衍生物。
以市售的唾液酸（Neu5Ac）為起始物，分別經過 17 步及 13 步可合成出 C-8 修飾成甲基的Neu5Ac8Me 和硫酸根的Neu5Ac8SO3-Na+，總產率分別為 12% 及 20%。相同的策略亦運用在合成神經節苷脂 LLG-5 非還原端的雙唾液酸（8-OMeNeuGcα2→11NeuGcα2）片段，另外，亦由（S）-甘油醛縮丙酮 48及 phosphonium salt 46為起始物經由 Wittig 反應，合成 LLG-5 另一核心片段─脂肪醯鏈，以利後續 LLG-5 之全合成研究。

Gangliosides play important roles in essential biological events including cellular recognition, cell-cell interaction, cell differentiation, and cellular transduction. In addition, the slight modification of terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) in the oligosaccharide chain of ganglioside imparts changes in biological activities of the parent gangliosides. The O-methylation and O-sulfation at C-8 position of non-reducing end Neu5Ac are the two most common modification, especially found in ethinodermatous gangliosides (EGs). The C-8 methylated or sulfated EGs displayed a broad spectrum neuritogenic activity on rat pheochromocytoma PC-12 cell in the presence of nerve growth factor. Consequently, EGs are regarded as potential drug to cure nervous system diseases such as Parkinson's disease.
In order to synthesize C-8 modified Neu5Ac derivatives, this thesis has developed a new chemical strategy by changing N3 in place of NHAc at the C-5 position of Neu5Ac to avoid competing N-methylation. The C-8 modified Neu5Ac derivatives, Neu5Ac8Me and Neu5Ac8SO3-Na+, were successfully synthesized by a linear 17-and 13-step sequences, with an overall yields of 12% and 20%, respectively, starting from Neu5Ac. Furthermore, the C-8 modified non-reducing end disialic acid (8-OMeNeuGcα2→11NeuGcα2) of the LLG-5 ganglioside was also prepared by following similar approach. On the other hand, the fatty acyl chain of the ganglioside LLG-5 was synthesized via the Wittig reaction using acetonide-protected (S)-glyceraldehyde 48 and phosphonium salt 46. The assembly moieties of the C-8 modified 8-OMeNeuGcα2→11NeuGcα2 disialic acid and the fatty acyl chain towards the synthesis of LLG-5 is currently underway.

目錄
中文摘要 I
Abstract II
謝誌 IV
目錄 VI
圖目錄 VIII
流程圖目錄 X
表目錄 XI
縮寫表 XII
第一章 緒論 1
1-1 碳水化合物 1
1-2 唾液酸 （sialic acids） 2
1-3 常見的唾液酸修飾及其合成困難度 4
1-4 八號位置修飾之唾液酸衍生物 ─ 神經節苷脂 9
1-4-1 八號位置羥基甲基化的唾液酸 10
1-4-2 八號位置羥基硫酸化的唾液酸 13
1-5 唾液酸八號位置修飾的文獻回顧 16
1-5-1 唾液酸八號羥基甲基化的合成 17
1-5-2 唾液酸八號羥基硫酸化的合成 20
1-6 八號位置甲氧基化應用 ─ LLG-3文獻回顧 21
1-7 八號位置甲氧基化應用 ─ LLG-5的發現及研究 26
1-8 研究動機 27
第二章 結果與討論 29
2-1 LLG-5 合成溯徑分析 29
2-1-1 合成八號位置甲基化之唾液酸 30
2-1-2 合成雙唾液酸42 43
2-1-3 脂肪醯鏈（fatty acyl chain）之逆合成 44
2-2 合成八號位置硫酸化的唾液酸衍生物 50
2-3 合成全去保護的八號位置甲基化唾液酸 55
2-4 合成全去保護的八號位置硫酸化唾液酸 59
2-5 全去保護且修飾的唾液酸應用 60
第三章 結論 63
第四章 實驗部分 64
4-1 Reagents and Solvents 64
4-2 Spectra Notes 65
4-3 Synthetic Procedures and Characterization 65
第五章 參考文獻 111
附錄 119
附錄目錄 120

圖目錄
圖 一、常見的三種唾液酸 3
圖 二、唾液酸上乙醯基的轉移 9
圖 三、從哺乳類、棘皮動物中分離並鑑定其結構 13
圖 四、Inoue教授於海膽精子中分離出含硫酸根的唾液酸 14
圖 五、ManNAc經唾液酸醛縮酶催化，合成唾液酸的機制 16
圖 六、八號位置羥基甲基化合成策略 20
圖 七、唾液酸進行硫酸根反應 21
圖 八、LLG-3之結構 22
圖 九、Sato教授合成LLG-3醣體之逆合成分析 23
圖 十、Kiso教授合成LLG-3之逆合成分析 24
圖 十一、Withers教授合成LLG-3之逆合成分析 25
圖 十二、LLG-5及LLG-3之結構比較 27
圖 十三、運用化學合成或酵素方法合成含唾液酸之天然物 28
圖 十四、LLG-5 之逆合成分析 30
圖 十五、唾液酸衍生物21之 H-3eq 化學位移 31
圖 十六、化合物33的1H-1H COSY 37
圖 十七、化合物32、33氫譜對照圖 37
圖 十八、化合物37之1H-1H COSY 41
圖 十九、化合物37之HSQC 41
圖 二十、化合物37之HMBC 42
圖 二十一、化合物37之HMBC 42
圖 二十二、脂肪醯鏈的逆合成分析 45
圖 二十三、Baskaran 教授提出苯亞甲基選擇性開環並氧化之機構 49
圖 二十四、利用 DIBAL-H 將苯亞甲基選擇性開環之反應機構 50
圖 二十五、合成化合物65之合成策略 53
圖 二十六、合成 Neu5Ac8Me 之兩種合成策略 59
圖 二十七、胞苷單磷酸唾液酸合成示意圖 61

流程圖目錄
流程圖 一、合成丙烯醇的唾液酸21 31
流程圖 二、合成 C-4 及 C-9 乙醯保護基的唾液酸衍生物25 32
流程圖 三、化合物25進行兩種甲基化測試 33
流程圖 四、合成 4,7-O-benzoyl-9-O-TBDMS-5-azido 的唾液酸30 34
流程圖 五、化合物30進行甲基化測試 35
流程圖 六、化合物32進行甲基化測試 36
流程圖 七、合成4,7-O-acetyl-9-O-benzoyl-5-azido 的唾液酸36 38
流程圖 八、合成 LLG-5 片段的雙唾液酸42 44
流程圖 九、合成phosphonium salt 46 47
流程圖 十、合成雙醇化合物51 48
流程圖 十一、三個路徑進行選擇性保護雙醇及氧化 48
流程圖 十二、合成化合物70及61 52
流程圖 十三、路徑A之合成化合物65 54
流程圖 十四、路徑B之合成化合物65 55
流程圖 十五、策略一之合成化合物82 57
流程圖 十六、策略二之合成Neu5Ac8Me 79 58
流程圖 十七、合成 Neu5Ac8SO3-Na+ 88 60
流程圖 十八、測試化合物79及88對 CSS 之受質容忍度 62

表目錄
表 一、生物體中，含不同位置修飾的唾液酸 6
表 二、Higuchi 教授進行生物活性實驗的神經節苷脂 11
表 三、比較不同的方法，於唾液酸八號位置進行甲基化的反應 19
表 四、最佳化 O-甲基化條件 39
表 五、銅離子催化，進行格林納反應 46
表 六、硫酸基化反應 53

1. Axford, J. Glycobiology and medicine: an introduction. J. R. Soc. Med. 1997, 90, 260-264.
2. (a) Ress, D. K.; Linhardt, R. J. Sialic acid donors: Chemical synthesis and glycosylation. Curr. Org. Chem. 2004, 1, 31-46; (b) Yamada, H.; Harada, T.; Miyazaki, H.; Takahashi, T. One-pot sequential glycosylation: A new method for the synthesis of oligosaccharides. Tetrahedron Lett. 1994, 35, 3979-3982; (c) Sears, P.; Wong, C.-H. Toward automated synthesis of oligosaccharides and glycoproteins. Science 2001, 291, 2344-2350; (d) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Automated solid-phase synthesis of oligosaccharides. Science 2001, 291, 1523-1527.
3. Sears, P.; Wong, C. H. Intervention of carbohydrate recognition by proteins and nucleic acids. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 12086-12093.
4. (a) Blix, F. G.; Gottschalk, A.; Klenk, E. Proposed nomenclature in the field of neuraminic and sialic acids. Nature 1957, 179, 1088; (b) Heard, D. H. The chemistry and biology of sialic acids and related substances. Immunology 1961, 4, 486.
5. Faillard, H. The early history of sialic acids. Trends Biochem. Sci. 1989, 14, 237-241.
6. Chen, X.; Varki, A. ACS Chem. Biol. Advances in the biology and chemistry of sialic acids. 2010, 5, 163-176.
7. Brinkman-Van der Linden, E. C. M.; Sjoberg, E. R.; Juneja, L. R.; Crocker, P. R.; Varki, N.; Varki, A. Loss of N-glycolylneuraminic acid in human evolution. J. Biol. Chem. 2000, 275, 8633-8640.
8. Yu, H.; Cao, H.; Tiwari, V. K.; Li, Y.; Chen, X. Chemoenzymatic synthesis of C8-modified sialic acids and related α2–3- and α2–6-linked sialosides. Bioorg. Med. Chem. Lett. 2011, 21, 5037-5040.
9. Varki, A. Sialic acids in human health and disease. Trends Mol. Med. 2008, 14, 351-360.
10. Passaniti, A.; Hart, G. W. Cell surface sialylation and tumor metastasis. J. Biol. Chem. 1988, 263, 7591-7603.
11. (a) Yu, H.; Huang, S.; Chokhawala, H.; Sun, M.; Zheng, H.; Chen, X. Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural α-2,6-linked sialosides: A P. damsela α-2,6-sialyltransferase with extremely flexible donor–substrate specificity. Angew. Chem. Int. Ed. 2006, 45, 3938-3944; (b) Chen, X.; Varki, A. Advances in the biology and chemistry of sialic acids. ACS chemical biology 2010, 5, 163-176.
12. Angata, T.; Varki, A. Chemical diversity in the sialic acids and related α-keto acids:  An evolutionary perspective. Chem. Rev. 2002, 102, 439-470.
13. Traving, C.; Schauer, R. Structure, function and metabolism of sialic acids. Cell. Mol. Life Sci. 1998, 54, 1330-1349.
14. Schauer, R. Achievements and challenges of sialic acid research. Glycoconjugate J. 2000, 17, 485-499.
15. Morley, T. J.; Withers, S. G. Chemoenzymatic synthesis and enzymatic analysis of 8-modified cytidine monophosphate-sialic acid and sialyl lactose derivatives. J. Am. Chem. Soc. 2010, 132, 9430-9437.
16. Hemeon, I.; Bennet, A. J. Sialic acid and structural analogues: stereoselective syntheses. Synthesis 2007, 2007, 1899-1926.
17. Liang, C.-F.; Kuan, T.-C.; Chang, T.-C.; Lin, C.-C. Stereoselective synthesis of S-linked α(2→8) and α(2→8)/α(2→9) hexasialic acids. J. Am. Chem. Soc. 2012, 134, 16074-16079.
18. Rich, J. R.; Withers, S. G. A chemoenzymatic total synthesis of the neurogenic starfish ganglioside LLG-3 using an engineered and evolved synthase. Angew. Chem. Int. Ed. 2012, 51, 8640-8643.
19. Tamai, H.; Ando, H.; Tanaka, H. N.; Hosoda-Yabe, R.; Yabe, T.; Ishida, H.; Kiso, M. The total synthesis of the neurogenic ganglioside LLG-3 isolated from the starfish Linckia laevigata. Angew. Chem. Int. Ed. 2011, 50, 2330-2333.
20. Sogabe, S.; Ando, H.; Koketsu, M.; Ishihara, H. A novel de-O-chloroacetylation reagent: 1-seleonocarbamoylpiperidine. Tetrahedron Lett. 2006, 47, 6603-6606.
21. Hadjiconstantinou, M.; Neff, N. H. GM1 Ganglioside: In vivo and in vitro trophic actions on central neurotransmitter systems. J. Neurochem. 1998, 70, 1335-1345.
22. (a) Schengrund, C. L. The role(s) of gangliosides in neural differentiation and repair: a perspective. Brain Res. Bull. 1990, 24, 131-141; (b) Manev, H.; Costa, E.; Wroblewski, J. T.; Guidotti, A. Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity. FASEB J. 1990, 4, 2789-2797.
23. Tagami, S.; Inokuchi, J.-I.; Kabayama, K.; Yoshimura, H.; Kitamura, F.; Uemura, S.; Ogawa, C.; Ishii, A.; Saito, M.; Ohtsuka, Y.; Sakaue, S.; Igarashi, Y. Ganglioside GM3 participates in the pathological conditions of insulin resistance. J. Biol. Chem. 2002, 277, 3085-3092.
24. Svennerholm, L. Gangliosides - a new therapeutic agent against stroke and Alzheimer's disease. Life Sci. 1994, 55, 2125-2134.
25. Schneider, J. S.; Gollomp, S. M.; Sendek, S.; Colcher, A.; Cambi, F.; Du, W. A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients. J. Neurol. Sci. 2013, 324, 140-148.
26. (a) Schengrund, C. L. Gangliosides: glycosphingolipids essential for normal neural development and function. Trends Biochem. Sci. 2015, 40, 397-406; (b) Molander-Melin, M.; Blennow, K.; Bogdanovic, N.; Dellheden, B.; Mansson, J. E.; Fredman, P. Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains. J. Neurochem. 2005, 92, 171-182.
27. Miyamoto, T.; Inagaki, M.; Isobe, R.; Tanaka, Y.; Higuchi, R.; Iha, M.; Teruya, K. Re-examination of the structure of acanthaganglioside C, and the identification of three minor acanthagangliosides F, G and H. Liebigs Ann. Recl. 1997, 1997, 931-936.
28. Kawano, Y.; Higuchi, R.; Komori, T. Isolation and structure of five new gangliosides. Liebigs Ann. Chem. 1990, 43-50.
29. Inagaki, M.; Isobe, R.; Higuchi, R. Isolation and structure of a new ganglioside molecular species. Eur. J. Org. Chem. 1999, 1999, 771-774.
30. Higuchi, R.; Inukai, K.; Jhou, J. X.; Honda, M.; Komori, T.; Tsuji, S.; Nagai, Y. Structure and biological activity of ganglioside molecular species. Liebigs Ann. Chem. 1993, 1993, 359-366.
31. Kaneko, M.; Kisa, F.; Yamada, K.; Miyamoto, T.; Higuchi, R. Structure of a new neuritogenic-active ganglioside from the sea cucumber stichopus japonicus. Eur. J. Org. Chem. 2003, 2003, 1004-1008.
32. Kawatake, S.; Inagaki, M.; Miyamoto, T.; Isobe, R.; Higuchi, R. Isolation and structure of a GM3-type ganglioside molecular species. Eur. J. Org. Chem. 1999, 1999, 765-769.
33. Inagaki, M.; Miyamoto, T.; Isobe, R.; Higuchi, R. Biologically active glycosides from Asteroidea, 43. Isolation and structure of a new neuritogenic-active ganglioside molecular species from the starfish Linckia laevigata. Chem. Pharm. Bull. 2005, 53, 1551-1554.
34. Yamada, K.; Matsubara, R.; Kaneko, M.; Miyamoto, T.; Higuchi, R. constituents of Holothuroidea. 10. Isolation and structure of a biologically active ganglioside molecular species from the sea cucumber Holothuria leucospilota. Chem. Pharm. Bull. 2001, 49, 447-452.
35. Kawatake, S.; Inagaki, M.; Isobe, R.; Miyamoto, T.; Higuchi, R. Isolation and structure of a GD3-type ganglioside molecular species possessing neuritogenic activity from the starfish Luidia maculata. Chem. Pharm. Bull. 2004, 52, 1002-1004.
36. Higuchi, R.; Inoue, S.; Inagaki, K.; Sakai, M.; Miyamoto, T.; Komori, T.; Inagaki, M.; Isobe, R. Biologically active glycosides from Asteroidea, 42. Isolation and structure of a new biologically active ganglioside molecular species from the starfish Asterina pectinifera. Chem. Pharm. Bull. 2006, 54, 287-291.
37. Higuchi, R.; Inagaki, M.; Yamada, K.; Miyamoto, T. Biologically active gangliosides from echinoderms. J. Nat. Med. 2007, 61, 367-370.
38. Kaneko, M.; Yamada, K.; Miyamoto, T.; Inagaki, M.; Higuchi, R. Neuritogenic activity of gangliosides from echinoderms and their structure–activity relationship. Chem. Pharm. Bull. 2007, 55, 462-463.
39. Ijuin, T.; Kitajima, K.; Song, Y.; Kitazume, S.; Inoue, S.; Haslam, S. M.; Morris, H. R.; Dell, A.; Inoue, Y. Isolation and identification of novel sulfated and nonsulfated oligosialyl glycosphingolipids from sea urchin sperm. Glycoconj. J. 1996, 13, 401-413.
40. Rockle, I.; Seidenfaden, R.; Weinhold, B.; Muhlenhoff, M.; Gerardy-Schahn, R.; Hildebrandt, H. Polysialic acid controls NCAM-induced differentiation of neuronal precursors into calretinin-positive olfactory bulb interneurons. Dev. Neurobiol. 2008, 68, 1170-1184.
41. Ando, H.; Koike, Y.; Koizumi, S.; Ishida, H.; Kiso, M. 1,5-Lactamized sialyl acceptors for various disialoside syntheses: Novel method for the synthesis of glycan portions of Hp-s6 and HLG-2 gangliosides. Angew. Chem. Int. Ed. 2005, 44, 6759-6763.
42. Svennerholm, L. Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method. Biochim. Biophys. Acta 1957, 24, 604-611.
43. Warren, L. The thiobarbituric acid assay of sialic acids. J. Biol. Chem. 1959, 234, 1971-1975.
44. Prokazova, N. V.; Mikhailov, A. T.; Kocharov, S. L.; Malchenko, L. A.; Zvezdina, N. D.; Buznikov, G.; Bergelson, L. D. Unusual gangliosides of eggs and embryos of the sea urchin Strongylocentrotus intermedius. Eur. J. Biochem. 1981, 115, 671-677.
45. Kochetkov, N. K.; Smirnova, G. P.; Chekareva, N. V. Isolation and structural studies of a sulfated sialosphingolipid from the sea urchin Echinocardium cordatum. Biochim. Biophys. Acta 1976, 424, 274-283.
46. Kitazume, S.; Kitajima, K.; Inoue, S.; Haslam, S. M.; Morris, H. R.; Dell, A.; Lennarz, W. J.; Inoue, Y. The occurrence of novel 9-O-sulfated N-glycolylneuraminic acid-capped α2 → 5-Oglycolyl-linked oligo/polyNeu5Gc chains in sea urchin egg cell surface glycoprotein. J. Biol. Chem. 1996, 271, 6694-6701.
47. Miyata, S.; Sato, C.; Kitamura, S.; Toriyama, M.; Kitajima, K. A major flagellum sialoglycoprotein in sea urchin sperm contains a novel polysialic acid, an alpha-2,9-linked poly-N-acetylneuraminic acid chain, capped by an 8-O-sulfated sialic acid residue. Glycobiology 2004, 14, 827-840.
48. Slomiany, B. L.; Kojima, K.; Banas-Gruszka, Z.; Murty, V. L.; Galicki, N. I.; Slomiany, A. Characterization of the sulfated monosialosyl triglycosyl ceramide from bovine gastric mucosa. Eur. J. Biochem. 1981, 119, 647-650.
49. Slomiany, A.; Kojima, K.; Banas-Gruszka, Z.; Slomiany, B. L. Structure of a novel sulfated sialoglycosphingolipid from bovine gastric mucosa. Biochem. Biophys. Res. Commun. 1981, 100, 778-784.
50. Yamakawa, N.; Sato, C.; Miyata, S.; Maehashi, E.; Toriyama, M.; Sato, N.; Furuhata, K.; Kitajima, K. Development of sensitive chemical and immunochemical methods for detecting sulfated sialic acids and their application to glycoconjugates from sea urchin sperm and eggs. Biochimie 2007, 89, 1396-1408.
51. Butor, C.; Higa, H. H.; Varki, A. Structural, immunological, and biosynthetic studies of a sialic acid-specific O-acetylesterase from rat liver. J. Biol. Chem. 1993, 268, 10207-10213.
52. Vandamme-Feldhaus, V.; Schauer, R. Characterization of the enzymatic 7-O-acetylation of sialic acids and evidence for enzymatic O-acetyl migration from C-7 to C-9 in bovine submandibular gland. J. Biochem. 1998, 124, 111-121.
53. Iwersen, M.; Vandamme-Feldhaus, V.; Schauer, R. Enzymatic 4-O-acetylation of N-acetylneuraminic acid in guinea-pig liver. Glycoconjugate J. 1998, 15, 895-904.
54. Tiralongo, J.; Schmid, H.; Thun, R.; Iwersen, M.; Schauer, R. Characterisation of the enzymatic 4-O-acetylation of sialic acids in microsomes from equine submandibular glands. Glycoconjugate J. 2000, 17, 849-858.
55. Kelm, A.; Shaw, L.; Schauer, R.; Reuter, G. The biosynthesis of 8-O-methylated sialic acids in the starfish Asterias rubens. Eur. J. Biochem. 1998, 251, 874-884.
56. Daniels, A. D.; Campeotto, I.; van der Kamp, M. W.; Bolt, A. H.; Trinh, C. H.; Phillips, S. E. V.; Pearson, A. R.; Nelson, A.; Mulholland, A. J.; Berry, A. Reaction mechanism of N-acetylneuraminic acid lyase revealed by a combination of crystallography, QM/MM simulation, and mutagenesis. ACS Chem. Biol. 2014, 9, 1025-1032.
57. Dufner, G.; Schwörer, R.; Müller, B.; Schmidt, R. R. Base- and sugar-modified cytidine monophosphate N-acetylneuraminic acid (CMP-Neu5Ac) analogues synthesis and studies with α(2-6)-Sialyltransferase from Rat Liver. Eur. J. Org. Chem. 2000, 2000, 1467-1482.
58. Al-Horani, R. A.; Desai, U. R. Chemical sulfation of small molecules – Advances and challenges. Tetrahedron 2010, 66, 2907-2918.
59. Tanaka, M.; Kai, T.; Sun, X.-L.; Takayanagi, H.; Furuhata, K. Synthesis of N-glycolyl-8-O-sulfoneuraminic acid. Chem. Pharm. Bull. 1995, 43, 2095-2098.
60. Hanashima, S.; Ishikawa, D.; Akai, S.; Sato, K. Synthesis of the starfish ganglioside LLG-3 tetrasaccharide. Carbohydr. Res. 2009, 344, 747-752.
61. Marra, A.; Sinay, P. Acetylation of N-acetylneuraminic acid and its methyl ester. Carbohydrate Research 1989, 190, 317-322.
62. Dabrowski, U.; Friebolin, H.; Brossmer, R.; Supp, M. 1H-NMR studies at N-acetyl-D-neuraminic acid ketosides for the determination of the anomeric configuration II. Tetrahedron Lett. 1979, 20, 4637-4640.
63. Van Der Vleugel, D. J. M.; Van Heeswijk, W. A. R.; Vliegenthart, J. F. G. A facile preparation of alkyl α-glycosides of the methyl ester of N-acetyl- D-neuraminic acid. Carbohydr. Res. 1982, 102, 121-130.
64. Roy, R.; Laferrière, C. A. Synthesis of protein conjugates and analogues of N-acetylneuraminic acid. Can. J. Chem. 1990, 68, 2045-2054.
65. 梁健夫，國立清華大學化學研究所 博士論文，民國98年。
66. Fan, G.-T.; Lee, C.-C.; Lin, C.-C.; Fang, J.-M. Stereoselective synthesis of Neu5Acα(2→5)Neu5Gc:  The building block of oligo/poly(→5-OglycolylNeu5Gcα2→) chains in sea urchin egg cell surface glycoprotein. J. Org. Chem. 2002, 67, 7565-7568.
67. Brook, M. A.; Chan, T. H. A simple procedure for the esterification of carboxylic-acids. Synthesis 1983, 201-203.
68. Yu, C.-S.; Niikura, K.; Lin, C.-C.; Wong, C.-H. The thioglycoside and glycosyl phosphite of 5-azido sialic acid: Excellent donors for the α-glycosylation of primary hydroxy groups. Angew. Chem. Int. Ed. 2001, 40, 2900-2903.
69. Demchenko, A. V.; Boons, G.-J. A novel direct glycosylation approach for the synthesis of dimers of N-acetylneuraminic acid. Chem. Eur. J. 1999, 5, 1278-1283.
70. Tanaka, H.; Nishiura, Y.; Takahashi, T. Stereoselective synthesis of oligo-α-(2,8)-sialic acids. J. Am. Chem. Soc. 2006, 128, 7124-7125.
71. Shirode, N. M.; Deshmukh, A. R. A. S. 4-Formylazetidin-2-ones, synthon for the synthesis of (2R,3S) and (2S,3R)-3-amino-2-hydroxydecanoic acid (AHDA). Tetrahedron 2006, 62, 4615-4621.
72. Liu, J.-H.; Jin, Y.; Long, Y.-Q. Synthesis of the C5–C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction. Tetrahedron 2010, 66, 1267-1273.
73. Xian, M.; Shuhler, B. J. Study of the synthesis of poecillanosine. Tetrahedron Lett. 2007, 48, 1209-1212.
74. Babu, K. C.; Ramadasu, G.; Gangaiah, L.; Madhusudhan, G.; Mukkanti, K. A new route for the synthesis of (R)-glyceraldehyde acetonide: A key chiral building block. Indian J. Chem., Sect B 2010, 41, 260-263.
75. Tamura, M.; Kochi, J. Coupling of grignard reagents with organic halides. Synthesis 1971, 6, 303-305.
76. Cahiez, G.; Chaboche, C.; Jézéquel, M. Cu-catalyzed alkylation of grignard reagents: A new efficient procedure. Tetrahedron 2000, 56, 2733-2737.
77. Kotra, L. P.; Xiang, Y.; Newton, M. G.; Schinazi, R. F.; Cheng, Y. C.; Chu, C. K. Structure-activity relationships of 2'-deoxy-2',2'-difluoro-L-erythro-pentofuranosyl nucleosides. J. Med. Chem. 1997, 40, 3635-3644.
78. Sugisaki, H.; Ruland, Y.; Baltas, M. Direct access to furanosidic eight-membered ulosonic esters from cis-α,β-epoxy aldehydes. Eur. J. Org. Chem. 2003, 2003, 672-688.
79. Kumar, P. S.; Banerjee, A.; Baskaran, S. Regioselective oxidative cleavage of benzylidene acetals: Synthesis of α- and β-benzoyloxy carboxylic acids. Angew. Chem. Int. Ed. 2010, 49, 804-807.
80. Yu, C.-C.; Withers, S. G. Recent developments in enzymatic synthesis of modified sialic acid derivatives. Adv. Synth. Catal. 2015, 357, 1633-1654.
81. Goto, K.; Suzuki, T.; Tamai, H.; Ogawa, J.; Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. Total synthesis and neuritogenic activity evaluation of ganglioside PNG-2A from the starfish protoreaster nodosus. Asian J. Org. Chem. 2015, 4, 1160-1171.
82. Liang, C.-F.; Yan, M.-C.; Chang, T.-C.; Lin, C.-C. Synthesis of S-linked α(2→9) octasialic acid via exclusive α S-glycosidic bond formation. J. Am. Chem. Soc. 2009, 131, 3138-3139.
83. Pan, Y.; Ayani, T.; Nadas, J.; Wen, S.; Guo, Z. Accessibility of N-acyl- D-mannosamines to N-acetyl-D-neuraminic acid aldolase. Carbohydr. Res. 2004, 339, 2091-2100.
84. Kumaraswamy, G.; Sadaiah, K.; Raghu, N. An organocatalytic enantioselective synthesis of (+)-duryne. Tetrahedron: Asymmetry 2012, 23, 587-593.
85. Al Dulayymi, J. A. R.; Baird, M. S.; Roberts, E. The synthesis of a single enantiomer of a major α-mycolic acid of M. tuberculosis. Tetrahedron 2005, 61, 11939-11951.
86. Schneider, R.; Freyhardt, C.; Schmidt, R. 5-Azido derivatives of neuraminic acid − Synthesis and structure. Eur. J. Org. Chem. 2001, 2001, 1655-1661.