PGL1與PGL2為2006年從台灣特有種溫泉菌Meiothermus taiwanensis NTU-220、Meiothermus rubber NTU-124、Thermus thermophilus NTU-077 及Thermus oshimai NTU-063純化分離之新型醣脂質，從M. taiwanensis 以及T. oshimai 分離出的PGL1具有調節與刺激人類單核白血球細胞分泌細胞激素proIL-1的功能，本篇論文發展一個控制立體選擇性以合成PGL1的方法。
在PGL1的合成中，關鍵的部分包含了以三氯乙醯亞胺酯醣予體 1 與D-lyxose衍生之一級醇醣受體 2 進行高度位向選擇性之醣基化反應，並於最後的合成階段引入磷脂質，即可以16個步驟總產率15%得到目標分子PGL1。在最後的階段將磷脂質與葡萄糖片段進行組裝提供了一個簡單的方法合成具有不同長度碳鏈之PGL1類似物，我們期望這樣的策略可有效率的建構醣脂質分子庫以應用SAR的探討。
SJG-2為第一個從海參Stichopus japonicus.純化分離出具有唾液酸支鏈醣體NeuAc24(NeuAc23)Gal與半乳糖胺之神經節苷脂，已證實在神經生長因子的輔助之下，可刺激大鼠嗜鉻細胞瘤分化為類神經細胞，由於這樣的生物活性較從哺乳類動物純化分離之GM1佳，因此棘皮類動物被認為是開發治療神經退化相關疾病之醣類藥物重要來源，本篇論文著重於探討如何建構SJG-2最具挑戰性之醣體片段Neu5Ac--(2,4)-Gal。
為了達到好的位向選擇性，我們合成半乳糖、還原形式之半乳糖及1,6-anhydrogalactose之醣受體，分別與數種唾液酸予體進行唾液酸醣基化反應。使用oxazolidinone-typed醣予體 50 與還原之半乳糖受體 70 進行唾液酸醣基化反應可得到單一位向產物，然而接下來的氧化反應失敗，無法得到目標分子，而使用N-phth-typed醣予體 88與1,6-anhydrogalactose之醣受體於唾液酸醣基化反應亦可得到好的位向選擇性產物，將目標雙醣分子應用於SJG-2支鏈三醣體之合成研究正在進行中。

PGL1 and PGL2 are new type glycolipids first isolated in 2006 from the thermophilic bacteria Thermus oshimai NTU-063, Thermus thermophilus NTU-077, Meiothermus ruber NTU-124, and Meiothermus taiwanensis NTU-220. PGL1 from M. taiwanensis and T.oshimai, but not T. thermophilus and M. rubber processes the activity to induce proIL-1 in human THP-1 monocytes and blood-isolated primary monocytes. In this thesis a method for the stereocontrolled synthesis of PGL1 is described.
The key features of the synthesis include a highly α-selective glycosylation reaction between a trichloroacetimidate donor with a D-lyxose-derived primary alcohol acceptor and incorporation of the phospholipids in the late‒stage of synthesis. The desired product, PGL1, was obtained in a total 15% yield over 16 steps. The late stage assembly of the phospholipids into the glycerate moiety of GlcNAc residue ensures easy access to PGL motifs with different lipids. We anticipate that synthetic access to PGLs and their analogs creating a convenient way in preparation of a library of compounds for structure–activity relationship studies.
SJG-2 is the first ganglioside containing either a branched sugar chain moiety NeuAc24(NeuAc23)Gal or a N-acetylgalactosamine residue isolated from sea cucumber Stichopus japonicus. In addition, SJG-2 exhibits neuritogenic activity toward rat pheochromocytoma cell line PC12 cells in the presence of NGF. Since the activities of some echinodermatous gangliosides are superior to that of mammalian ganglioside GM1, echinoderms are considered as an important source for the development of carbohydrate-based drugs used in the treatment of neurodegenerative diseases. Construction of the most challenging moiety, the Neu5Ac--(2,4)-Gal of SJG-2 was discussed in this thesis.
To achieve high -selectivity, three different types of acceptors, including galactopyranose, reducing-galactose and 1,6-anhydrogalactose acceptors were applied in sialylations with various donors. We use oxazolidinone-typed donor 50 and reducing-galactose acceptor 70 to do the sialylation can get exclusive  product, but the following oxidation reaction was failed. On the other hand, the glycosylation product obtained by using N-phth-typed donor 88 and 1,6-anhydrogalactose acceptors possess high -selectivity. The application of the desired sugar moiety toward the synthesis of branched sugar chain of SJG-2 is underway.

第三章、參考文獻與資料
(1) Hakomori, S.; Zhang,Y.-M. Glycosphingolipid antigens and cancer therapy. Chem. Biol. 1997, 4, 97-104.
(2) Bhat, S.; Spitalnik, S. L.; Gonzalezscarano, F.; Silberberg, D. H. Galactosyl ceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120. Proc. Natl. Acad. Sci. U. S. A. 1991, 88, 7131-7134.
(3) Karlesson, K. A. Microbial recognition of target-cell glycoconjugates. Curr. Opin. Struct. Biol. 1995, 5, 622-635.
(4) Yu, K. O. A.; Porcelli, S. A. The diverse functions of CD1d-restricted NKT cells and their potential for immunotherapy. Immunol. Lett. 2005, 100, 42-55.
(5) Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.; Fukushima, H. Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice. J. Med. Chem. 1995, 38, 2176-2187.
(6) Kawano, T.; Cui, J. Q.; Koezuka, Y.; Toura, I.; Kaneko, Y.; Motoki, K.; Ueno, H.; Nakagawa, R.; Sato, H.; Kondo, E.; Koseki, H.; Taniguchi, M. CD1d-restricted and TCR-mediated activation of V14 NKT cells by glycosylceramides. Science 1997, 278, 1626-1629.
(7) Paulick, M. G.; Bertozzi, C. R. The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry 2008, 47, 6991-7000.
(8) Bartke, N.; Hannun, Y. A. Bioactive sphingolipids: metabolism and function. J. Lipid Res. 2009, 50, S91-S96
(9) Hannuun, Y. A.; Obeid, L. M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 2008, 9, 139-150.
(10) Goldsby, R. A.; Kindt, T. J.; Osborne, B. A. Immunology, 5th ed. 2000, W. H. Freeman company, New York.
(11) Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell 2010, 140, 805-820.
(12) De Libero, G.; Mori, L. Recognition of lipid antigens by T cells. Nat. Rev. Immunol. 2005, 5, 485-496.
(13) Wu, D.; Fujio, M.; Wong, C.-H. Glycolipids as immunostimulating agents. Bioorg. & Med. Chem. 2008, 16, 1073-1083.
(14) Akira, S.; Takeda, K.; Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2001, 2, 675-680
(15) Aderem, A.; Ulevitch, R. J. Toll-like receptors in the induction of the innate immune response. Nature 2000, 406, 782-787.
(16) Mattner, J.; DeBord, K. L.; Ismail, N.; Goff, R. D.; Cantu III, C.; Zhou, D.; Saint-Mezard, P.; Wang, V.; Gao, Y.; Yin, N.; Hoebe, K.; Schneewind, O.; Walker, D.; Beutler, B.; Teyton, L.; Savage, P. B.; Bendelac, A. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 2005, 434, 525-529.
(17) Paget, C.; Mallevaey, T.; Speak, A. O.; Torres, D.; Fontaine, J.; Sheehan, K. C. F.; Capron, M.; Ryffel, B.; Faveeuw, C.; Leite de Moraes, M.; Platt, F.; Trottein, F. Activation of invariant NKT cells by TLR9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. Immunity 2007, 27, 597-609.
(18) Salio, M.; Speak, A. O.; Shepherd, D.; Polzella, P.; Illarionov, P. A.; Veerapen, N.; Besra, G. S.; Platt, F. M.; Cerundolo, V. Modulation of human naturel killer T cell ligands on TLR-mediated antigen-presenting cell activation. Proc. Natl. Acad. Sci. USA 2007, 104, 20490-20495.
(19) Cerundolo, V.; Silk, J. D.; Hajar Masri, S.; Salio, M. Harnessing invariant NKT cells in vaccination strategies Nat. Rev. Immuno. 2009, 9, 28-38.
(20) Christian, R. H. R.; Whitfield, C. Lipopolysacchariide endotoxins. Annu. Rev. Biochem. 2002, 71, 635-700.
(21) Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 2003, 67, 593-656.
(22) Westphal, O. Bacterial endotoxins. The second Carl Prausnitz Memorial Lecture. Int. Arch. Allergy Immuno. 1975, 49, 1-43.
(23) Cohen, J. The immunopathogenesis of sepsis. Nature, 2002, 420, 885-891.
(24) Schletter, J.; Heine, H.; Ulmer, A. J.; Rietschel, E. T. Molecular mechanisms of endotoxin activity. Arch. Microbiol. 1995, 164, 383-389.
(25) Lynn, D. H.; William, J. C.; Daniel, P. R. Inhibition of endotoxin response by synthetic TLR4 antagonists. Curr. Top. Med. Chem. 2004, 4, 1147-1171.
(26) Luke, A. J. O. N. When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunol. Rev. 2008, 29, 12-20.
(27) Akira, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006, 124, 783-801.
(28) Palsson-McDermott, E. M.; O'Neill, L. A. J. Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology 2004, 113, 153-162.
(29) Didonato, J. A.; Hayakawa, M.; Rothwarf, D. M.; Zandi, E.; Karin, M. A cytokine-responsive IB kinase that activates the transcription factor NF-B. Nature 1997, 388, 548-554.
(30) http://www.invivogen.com/docs/Insight200705.pdf accessed in 2008/08/17.
(31) Christ, W. J.; Asano, O.; Robidoux, A. L.; Perez, M.; Wang, Y.; Dubuc, G. R.; Gavin, W. E.; Hawkins, L. D.; McGuinness, P. D.; Mullarkey, M. A. E5531, a pure endotoxin antagonist of high potency. Science 1995, 268, 80-83.
(32) Mullarkey, M.; Rose, J. R.; Bristol, J.; Kawata, T.; Kimura, A.; Kobayashi, S.; Przetak, M.; Chow, J.; Gusovsky, F.; Christ, W. J.; Rossignol, D. P. Inhibition of endotoxin response by E5564, a novel Toll-like receptor 4-directed endotoxin antagonist. J. Pharmacol. Exp. Ther. 2003, 304, 1093-1102.
(33) Savov, J. D.; Brass, D. M.; Lawson, B. L.; McElvania-Tekippe, E.; Walker, J. K. L.; Schwartz, D. A. “Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide.” Am. J. Physiol. Lung Cell Mol. Physiol. 2005, 289, L329-337.
(34) Jiang, Z.-H.; Budzynski, W. A.; Skeels, L. N.; Krantz, M. J.; Koganty, R. R. Novel lipid A mimetics derived from pentaerythritol: synthesis and their potent agonistic activity. Tetrahedron 2002, 58, 8833-8842.
(35) Tamai, R.; Asai, Y.; Hashimoto, M.; Fukase, K.; Kusumoto, S.; Ishida, H.; Kiso, M.; Ogawa, T. Cell activation by monosaccharide lipid A analogues utilizing Toll-like receptor 4. Immunology 2003, 110, 66-72.
(36) Takayama, K.; Ribi, E.; Cantrell, J. L. Isolation of a Nontoxic Lipid A Fraction Containing Tumor Regression Activity. Cancer Res. 1981, 41, 2654-2657.
(37) Vuopio-Varkila, J.; Nurminen, M.; Pyhala, L.; Makela, P. H. Lipopolysaccharide- induced non-specific resistance to systemic Escherichia coh infection in mice. J. Med. Microbiol. 1988, 25, 197-203.
(38) Vernacchio, L.; Bernstein, H.; Pelton, S.; Allen, C.; MacDonald, K.; Dunn, J.; Duncan, D. D.; Tsao, G.; LaPosta, V.; Eldridge, J.; Laussucq, S.; Ambrosino, D. M.; Molrine, D. C. Effect of monophosphoryl lipid A (MPL (R)) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers. Vaccine 2002, 20, 3658-3667.
(39) Evans, J. T.; Cluff, C. W.; Johnson, D. A.; Lacy, M. J.; Persing, D. H.; Baldridge, J. R. Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert Rev. Vaccines 2003, 2, 219-229.
(40) Fischer, K.; Scotet, E.; Niemeyer, M.; Koebernick, H.; Zerrahn, J.; Maillet, S.; Hurwitz, R.; Kursar, M.; Bonneville, M.; Kaufmann, S. H. E.; Schaible, U. E. Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 10685-10690.
(41) Brigl, M.; Brenner, M. B. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 2004, 22, 817-890.
(42) Kinjo, Y.; Tupin, E.; Wu, D.; Fujio, M.; Garcia-Navarro, R.; Rafii-El-Idrissi Benhnia, M.; Zajonc, D. M.; Ben-Menachem, G.; Ainge, G. D.; Painter, G. F.; Khurana, A.; Hoebe, K.; Behar, S. M.; Beutler, B.; Wilsom, I. A.; Tsuji, M.; Sellati, T. J.; Wong, C.-H.; Kronenberg, M. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nature Immunol. 2006, 7, 978-986.
(43) Kinjo, Y.; Wu, D.; Kim, G.; Xing, G.-W.; Poles, M. A.; Ho, D.-D.; Tsuji, M.; Kawahara, K.; Wong, C.-H.; Kronenberg, M. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 2005, 434, 520-525.
(44) Kinjo, Y.; Pei, B.; Bufali, S.; Raju, R.; Richardson, S. K.; Imamura, M.; Fujio, M.; Wu, D.; Khurana, A.; Kawahara, K.; Wong, C.-H.; Howell, A. R.; Seeberger, P.; Kronenberg, M. Natural sphingomonas glycolipids vary greatly in their ability to activate natural killer T cells. Chem. Biol. 2008, 15, 654-664.
(45) Olano, J. P.; Walker, D. H. Human ehrlichioses. Med. Clin. North Am. 2002, 86, 375-392.
(46) Amprey, J. L.; Im, J. S.; Turco, S. J.; Murray, H. W.; Illarionov, P. A.; Besra, G. S.; Porcelli, S. A.; Spath, G. F. A subset of liver NKT cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. J. Exp. Med. 2004, 200, 895-904.
(47) Orloski, K. A.; Hayes, E. B.;Campbell, G. L.; Dennis, D. T. Surveillance for Lyme disease--United States, 1992-1998. MMWR CDC Surveill. Summ. 2000, 49, 1-11
(48) Yang, Y.-L.; Yang, F.-L.; Jao, S.-C.; Chen, M.-Y.; Tsay, S.-S.; Zou, W.; Wu. S.-H. Structural elucidation of phosphoglycolipids from strains of the bacterial thermophiles Thermus and Meiothermus. J. Lipid Res. 2006, 47, 1823-1832.
(49) Yang, F.-L.; Hua, K.-F.; Yang, Y.-L.; Zou, W.; Chen, Y.-P.; Liang, S.-M.; Hsu, H.-Y.; Wu. S.-H. TLR-independent induction of human monocyte IL-1 by phosphoglycolipids from thermophilic bacteria. Glycoconjugate J. 2008, 25, 427-439.
(50) Loppnow, H.;Werdan, K.; Reuter, G.; Flad, H.D. The interleukin-1 and interleukin-1 converting enzyme families in cardiovascular system. Eur. Cytokine. Netw. 1998, 9, 675-680.
(51) Xaus, J.; Comalada, M.; Valledor, A. F.; Lloberas, J. Lopez-Soriano, F.; Argiles, J.M.; Yang, J.; Hooper, W.C.; Phillips, D.J.; Talkington, D.F. Interleukin-1 beta responses to Mycoplasma pneumoniae infection are cell-type specific. Microb. Pathog. 2003, 34, 17-25.
(52) Petitou, M.; van Boeckel, C. A. A. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew. Chem., Int. Ed. 2004, 43, 3118-3133.
(53) Echardt, K. Tunicamycins, streptovirudins and corynetoxins. A special subclass of nucleotide antibiotics. J. Nat. Prod. 1983, 46, 544-550.
(54) Magnet, S.; Blanchard, J. S. Molecular insights into aminoglycoside action and resistance. Chem. Rev. 2005, 105, 477-497.
(55) Danishefsky, S. J.; Allen, J. R. From the laboratory to the clinic: a retrospective on fully synthetic carbohydrate-based anticancer vaccines. Angew. Chem., Int. Ed. 2000, 39, 836-863.
(56) Marcaurelle, L. A.; Bertozzi, C. R. Recent advances in the chemical synthesis of mucin-like glycoproteins. Glycobiology 2002, 12, 69R-77R.
(57) Ferguson, M. A. J.; Williams, A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu. Rev. Biochem. 1988, 57, 285-320.
(58) Boltje, T. J.; Buskas, T.; Boons, G. J. Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research. Nature Chem. 2009, 1, 611-622.
(59) Nigudkar, S. S.; Demchenko, A. V. Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry. Chem. Sci. 2015, 6, 2687-2704.
(60) Carmona, A. T.; Moreno-Vargas, A. J.; Robina, I. Stereoselective synthesis of 1,2-cis-glycosylic linkages. Carbohydr. Chem. 2009, 35, 33-70.
(61) Crich, D.; Cai, W. Chemistry of 4,6-O-benzylidene-D-glycopyranosyl triflates: contrasting behavior between the gluco and manno series. J. Org. Chem. 1999, 64, 4926-4930.
(62) Benakli, K.; Zha, C.; Kerns, R. J. Oxazolidinone protected 2 amino 2 deoxy D-glucose derivatives as versatile intermediates in stereoselective oligosaccharide synthesis and the formation of alpha-linked glycosides. J. Am. Chem. Soc. 2001, 123, 9461-9462.
(63) Olsson, J. D.; Eriksson, L.; Lahmann, M.; Oscarson, S. Investigations of glycosylation reactions with 2-N-acetyl-2N,3O-oxazolidinone-protected glucosamine donors. J. Org. Chem. 2008, 73, 7181-7188.
(64) Manabe, S.; Ishii, K.; Hashizume, D.; Koshino, H.; Ito, Y. Evidence for endocyclic cleavage of conformationally restricted glycopyranosides. Chem. Eur. J. 2009, 15, 6894-6901.
(65) Manabe, S.; Ito, Y. Pyranosides with 2,3-trans carbamate groups: exocyclic or endocyclic cleavage reaction? Chem. Rec. 2014, 14, 502-515.
(66) Imamura, A.; Ando, H.; Korogi, S.; Tanabe, G.; Muraoka, O.; Ishida, H.; Kiso, M. Di-tert-butylsilylene (DTBS) group-directed α-selective galactosylation unaffected by C-2 participating functionalities. Tetrahedron Lett. 2003, 44, 6725-6728.
(67) Hara, A.; Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. A new chemical approach to human ABO histo-blood group type 2 antigens. Molecules, 2014, 19, 414-437.
(68) Kim, J. H.; Yang, H.; Park, J.; Boons, G. J. A general strategy for stereoselective glycosylations. J. Am. Chem. Soc. 2005, 127, 12090-12097.
(69) Boltje, T. J.; Kim, J.-H.; Park, J.; Boons, G. J. Chiral-auxiliary-mediated 1,2-cis-glycosylations for the solid-supported synthesis of a biologically important branched -glucan. Nature Chem. 2010, 2, 552-557.
(70) Fan, T.; Mo, K. F.; Boons, G. J. Stereoselective assembly of complex oligosaccharides using anomeric sulfonium ions as glycosyl donors. J. Am. Chem. Soc. 2012, 134, 7545-7552.
(71) Demchenko, A. V.; Rousson, E.; Boons, G. J. Stereoselective 1,2-cis- galactosylation assisted by remote neighboring group participation and solvent effects. Tetrahedron Lett. 1999, 40, 6523-6526.
(72) Takatani, M.; Matsuo, I.; Ito, Y. Pentafluoropropionyl and trifluoroacetyl groups for temporary hydroxyl group protection in oligomannoside synthesis. Carbohydr. Res. 2003, 338, 1073-1081.
(73) Cheng, Y.-P.; Chen, H.-T.; Lin, C.-C. A convenient and highly stereoselective approach for-galactosylation performed by galactopyranosyl dibenzyl phosphite with remote participating groups Tetrahedron Lett. 2002, 43, 7721- 7723.
(74) Kalikanda, J.; Li, Z. Study of the stereoselectivity of 2-azido-2-deoxygalactosyl donors: remote protecting group effects and temperature dependency. J. Org. Chem. 2011, 76, 5207-5218.
(75) Ngoje, G.; Li, Z. Study of the stereoselectivity of 2-azido-2-deoxyglucosyl donors: protecting group effects. Org. Biomol. Chem. 2013, 11, 1879-1886.
(76) Pilgrim, W.; Murphy, P. V. -Glycosphingolipids via chelation-induced anomerization of O- and S-glucuronic and galacturonic acid derivatives. Org. Lett. 2009, 11, 939-942.
(77) Jones, P. G.; Kirby, A. J.; Komarov, I. V.; Wothers, P. D. A test for the reverse anomeric effect. Chem. Commun. 1998, 1695-1696.
(78) Demchenko, A. V.; Stauch, T.; Boons, G. J. Solvent and other effects on the stereoselectivity of thioglycoside glycosidations. Synlett. 1997, 818-820.
(79) Koshiba, M.; Suzuki, N.; Arihara, R.; Tsuda, T.; Nambu, H.; Nakamura, S.; Hashimoto, S. Catalytic stereoselective glycosidation with glycosyl diphenyl phosphates: rapid construction of 1,2-cis--Glycosidic Linkages. Chem. Asian J. 2008, 3, 1664-1677.
(80) Lu, S.-R.; Lai, Y.-H.; Chen, J.-H.; Liu, C.-Y.; Mong, K.-K. Dimethylformamide: an unusual glycosylation modulator. Angew. Chem., Int. Ed. 2011, 50, 7315 -7320.
(81) Li, Z.; Gildersleeve, J. C. Mechanistic studies and methods to prevent aglycon transfer of thioglycosides. J. Am. Chem. Soc. 2006, 128, 11612-11619.
(82) Liu, C.-Y.; Mulani, S.; Mong, K.-K. Iterative one-pot -glycosylation strategy: application to oligosaccharide synthesis. Adv. Synth. Catal. 2012, 354, 3299- 3310.
(83) Park J.; Kawatkar, S.; Kim, J. H.; Boons, G. J. Stereoselective glycosylations of 2-azido-2-deoxy-glucosides using intermediate sulfonium ions. Org. Lett. 2007, 9, 1959-1962.
(84) Chu, A.-H. A.; Nguyen, S. H.; Sisel, J. A.; Minciunescu, A.; Bennett, C. S. Selective synthesis of 1,2-cis--glycosides without directing groups. application to iterative oligosaccharide synthesis. Org. Lett. 2013, 15, 2566-2569.
(85) Mensah, E. A.; Nguyen, H. M. Nickle-catalyzed stereoselective formation of -2-deoxy-2-amino glycosides. J. Am. Chem. Soc. 2009, 131, 8778-8780.
(86) Yasomanee, J. P.; Demchenko, A. V. Effect of remote picolinyl and picoloyl substituents on the stereoselectivity of chemical glycosylation. J. Am. Chem. Soc. 2012, 134, 20097-20102.
(87) Yasomanee, J. P.; Demchenko, A. V. Hydrogen-bond mediated aglycone delivery (HAD): a highly stereoselective synthesis of 1,2-cis -D-glucosides from common glycosyl donors in the presence of bromine. Chem. Eur. J. 2015, 21, 1 -11.
(88) Hoang, K. L. M.; Liu, X.-W. The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction. Nat. Commun. 2014, 5, 5051-5060.
(89) Guo, X.; Jiang, P.; Fu, H.; Jiang, Y.; Zhao, Y. New and one pot chemoselective synthesis of nucleoside 5’-H-phosphonate diesters. Nucleos. Nucleot. Nucl. 2005, 9, 1325-1331.
(90) Swarts, B. M.; Guo, Z. Synthesis of a glycosylphosphatidylinositol anchor bearing unsaturated lipid chains. J. Am. Chem. Soc. 2010, 132, 6648-6650.
(91) Liu, X.; Stocker, B.; Seeberger, P. H. Total synthesis of phosphatidylinositol mannosides of mycobacterium tuberculosis. J. Am. Chem. Soc. 2006, 128, 3638-3648.
(92) Berkin, A.; Coxon, B.; Pozsgay, V. Towards a synthetic glycoconjugate vaccine against Neisseria meningitidis A. Chem. Eur. J. 2002, 8, 4424-4433.
(93) Avramopoulou, V.; Antonopoulou, S.; Argyropoulos, D.; Froussios, C.; Demopoulos, C. A. Synthesis of a new phosphoglycolipid with biological activity towards platelets. Int. J. Biochem. Cell Biol. 1997, 29, 767-774.
(94) Bannwarth, W.; Trzeciak, A. A simple and effective chemical phosphorylation procedure for biomolecules. Helv. Chim. Acta 1987, 70, 175-186.
(95) Fan, G.-T.; Pan, Y.-S.; Lu, K.-C.; Cheng, Y.-P.; Lin, W.-C.; Lin, S.; Lin, C.-H.; Wong, C.-H.; Fang, J.-M.; Lin, C.-C. Synthesis of -galactosyl ceramide and the related glycolipids for evaluation of their activities on mouse splenocytes. Tetrahedron 2005, 61, 1855-1862.
(96) Hung, L.-C.; Lin, C.-C.; Hung, S.-K.; Wu, B.-C.; Jan, M.-D.; Liou, S.-H.; Fu, S. -L. A synthetic analog of alpha-galactosylceramide induces macrophage activation via the TLR4-signaling pathways. Biochem. Pharmacol. 2007, 73, 1957-1970.
(97) Huang, L.-D.; Lin, H.-J.; Huang, P.-H.; Hsiao, W.-C.; Reddy, L. V. R.; Fu, S.-L.; Lin, C.-C. Synthesis of serine-based glycolipids as potential TLR4 activators. Org. Biomol. Chem. 2011, 9, 2492-2504.
(98) Lin, Y.-S.; Huang, L.-D.; Lin, C.-H.; Huang, P.-H.; Chen, Y.-J.; Wong, F.-H.; Lin, C.-C.; Fu, S.-L. In vitro and in vivo anticancer activity of a synthetic glycolipid as Toll-like receptor 4 (TLR4) activator. J. Biol. Chem. 2011, 286, 43782-43792.
(99) Guthridge, C. J.; Gabay, C. Interleukin-1 receptor antagonist; role in biology. Annu. Rev. Immunol. 1998, 16, 27-55.
(100) 林虹君，國立清華大學化學研究所 碩士論文，醣脂質之合成，民國99年.
(101) Mayer, T. G.; Kratzer, B.; Schmidt, R. R. Synthesis of a GPI anchor of yeast (Saccharomyces cerevisiae). Angew. Chem., Int. Ed. 1994, 33, 2177-2181.
(102) Carlsen, H. J. Katsuki, T. Martin, V. S.; Sharpless, K. B. A greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compounds. J. Org. Chem. 1981, 46, 3936-3938.
(103) Webster, F. X.; Silverstein, R. M. Synthesis of optically pure enantiomers of grandisol. J. Org. Chem. 1986, 51, 5226-5231.
(104) Ren, C.-T.; Tsai, Y.-H.; Yang, Y.-L.; Zou, W.; Wu, S.-H. Synthesis of a tetrasaccharide glycosyl glycerol precursor to glycolipids of Meiothermus taiwanensis ATCC BAA-400. J. Org. Chem. 2007, 72, 5427-5430.
(105) Altona, C.; Haasnoot, C. A. G. Prediction of anti and gauche vicinal proton- proton coupling constants in carbohydrates: A simple additivity rule for pyranose rings. Org. Magn. Reson. 1980, 13, 417-429.
(106) Lindhorst, T. K. Essentials of carbohydrate chemistry and biochemistry. Wiley-Vch, Weinheim, 2000, pp. 199-207.
(107) Kraus, G. A.; Roth, B. Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system. J. Org. Chem. 1980, 45, 4825-4830.
(108) Foglia, T. A.; Vail, P. D. An efficient large-scale synthesis of triisopentadecanoin. Org. Prep. Proc. Int. 1993, 25, 209-213.
(109) Partha G.; Vikas, K.; Arun K. S. A convergent total synthesis of a new antiepileptic ceramide and its triacetyl derivative using olefin cross metathesis. Tetrahedron 2010, 66, 7504-7509.
(110) Lee, J.-G.; Ueno, M.; Miyajima, Y.; Nakamura, H. Synthesis of boron cluster lipids: closo-Dodecaborate as an alternative hydrophilic function of boronated liposomes for neutron capture therapy. Org. Lett. 2007, 9, 323-326.
(111) Martin, S. F.; Josey, J. A.; Wong, Y. L.; Dean, D. W. General method for the synthesis of phospholipid derivatives of 1,2-O-diacyl-sn-glycerols. J. Org. Chem. 1994, 59, 4805-4820.
(112) Kajihara, Y.; Kamitani, T.; Sato, R.; Kamei, N.; Miyazaki, T.; Okamoto, R.; Sakakibara, T.; Tsuji, T.; Yamamoto, T. Synthesis of CMP-9”-modified-sialic acids as donor substrate analogues for mammalian and bacterial sialyltransferases. Carbohydr. Res. 2007, 342, 1680-1688.
(113) Xue, J.; Guo, Z. Convergent synthesis of a GPI containing an acylated inositol. J. Am. Chem. Soc. 2003, 125, 16334-16339.
(114) Fujimoto, Y.; Mitsunobe, K.; Fujiwara, S.; Mori, M.; Hashimoto, M.; Suda, Y.; Kusumotoa, S.; Fukase, K. Synthesis and biological activity of phospho- glycolipids from Thermus thermophiles. Org. Biomol. Chem. 2013, 11, 5034-5041.
(115) Geng, Y.; Zhang, L.-H.; Ye, X.-S. Stereoselectivity investigation on glycosylation of oxazolidinone protected 2-amino-2-deoxy-D-glucose donors based on pre-activation protocol. Tetrahedron 2008, 64, 4949-4958.
(116) Lin, C.-C.; Fan, G.-T.; Fang, J.-M. A concise route to phytosphingosine from lyxose. Tetrahedron Lett. 2003, 44, 5281-5283.
(117) Chang, C.-W.; Chen, Y.-N.; Adak, A. K.; Lin, K.-H.; Tzoua, D.-L. M.; Lin, C.-C. Synthesis of phytosphingosine using olefin cross-metathesis: a convenient access to chain-modified phytosphingosines from D-lyxose. Tetrahedron 2007, 63, 4310-4318.
(118) Hadjiconstantinou, M.; Neff, N. H. GM1 Ganglioside: In vivo and in vitro trophic actions on central neurotransmitter systems J. Neurochem. 1998, 70, 1335-1345.
(119) Sonnino, S.; Chigorno, V. Ganglioside molecular species containing C18- and C20-sphingosine in mammalian nervous tissues and neuronal cell cultures. Biochim. Biophy. Acta 2000, 1469, 63-77.
(120) Schengrund, C. L. The role(s) of gangliosides in neural differentiation and repair: a perspective. Brain Res. Bull. 1990, 24, 131-141.
(121) Cuello, A. C. Glycosphingolipids that can regulate nerve growth and repair. Adv. Pharmacol. 1990, 21, 1-50.
(122) Zeller, C. B.; Marchase, R. B. Gangliosides as modulators of cell function. Am. J. Physiol. 1992, 262, C1341-C1355.
(123) 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.
(124) Schneider, J. S.; DiStefano, L. Oral administration of semisynthetic sphingolipids promotes recovery of striatal dopamine concentrations in a murine model of parkinsonism. Neurology, 1994, 44, 748-750.
(125) Kojima, N.; Kurosawa, N.; Nishi, T.; Hanai, N.; Thuji, S. Induction of cholinergic differentiation with neurite sprouting by de novo biosynthesis and expression of GD3 and b-series gangliosides in Neuro2a cells. J. Biol. Chem. 1994, 269, 30451-30456.
(126) Schnaar, R. L. Glycosphingolipids in cell surface recognition. Glycobiology, 1991, 1, 477-485.
(127) Tiemeyer, M.; asuda. Y. Y.; Schnaars, R. L. Ganglioside-specific binding protein on rat brain membranes J. Biol. Chem. 1989, 264, 1671-1681.
(128) Kojima, N.; Hakomori, S. Specific interaction between gangliotriaosylceramide (Ggs) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. J. Biol. Chem. 1989, 264, 20159-20162.
(129) Suzuki, Y.; Nakao, T.; Ito, T.; Watanabe, N.; Toda, Y. Guiyun, X.; Suzuki, T.; Kobayashi, T.; Kimura, Y.; Yamada, A.; Sugawara, K.; Nishimura, H.; Kitame, F.; Nakamura, K.; Deya, E.; Kiosi, M.; Hasegawa, A. Structural determination of gangliosides that bind to influenza A, B, and C viruses by an improved binding assay: strain-specific receptor epitopes in sialo-sugar chains. Virology 1992, 189, 121-131.
(130) Tagami, S.; Inokuchi, J.; 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.
(131) Farooqui, T.; Franklin, T.; Pearl, D. K.; Yates, A. J. Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J. Neurochem. 1997, 68, 2348-2355.
(132) Hakomori, S. Bifunctional role of glycosphingolipids. J. Biol. Chem. 1990, 265, 18713-18716.
(133) Hakomori, S. Glycosphingolipids in cellular interaction, differentiation, and oncogenesis. Annu. Rev. Biochem. 1981, 50, 733-764.
(134) Simons, K.;Toomre, D. Lipid rafts and signal transduction. Nat. Rev. 2000, 1, 31-39.
(135) Mutoh, T.; Tokuda, A.; Miyadai, T.; Hamaguchi, M.; Fujiki, N. Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 5087-5091.
(136) Nobile-Orazio, E.; Carpo M.; Scarlato, G. Gangliosides. Their role in clinical neurology. Drugs 1994, 47, 576-585.
(137) Macher, B. A.; Sweeley, C. C. Glycosphingolipids: Structure, biological source, and properties. Methods Enzymol. 1978, 50, 236-251.
(138) Lee, W. M. F.; Westrick, M. A.; Macher, B. A. High-Performance liquid chromatography of long-chain neutral glycosphingolipids and gangliosides. Biochim. Biophys. Acta 1982, 712, 498-504.
(139) Svennerholm, L.; Bostrom, K.; Fredman, P.; Jungbjer, B.; Lekman, A.; Mansson, J. E.; Rynmark, B. M. Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord. Biochim Biophys Acta. 1994, 15, 115-123.
(140) Higuchi, R.; Inagaki, M.; Yamada, K.; Miyamoto, T. Biologically active gangliosides from echinoderms. J. Nat. Med. 2007, 61, 367-370.
(141) 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.
(142) Kaneko, M.; Kisa, F.; Yamada, K.; Miyamoto, T.; Higuchi, R. Structure of a new neuritogenic-active ganglioside from the sea cucumber Stichopus japonicas. Eur. J. Org. Chem. 2003, 1004-1008.
(143) Fiore, M.; Chaldakov, G.; Aloe, L. Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Rev Neurosci 2009, 20, 133-145.
(144) Cheung, W.-M.; Hui, W.-S.; Chu, P.-W.; Chiu, S.-W.; Ip, N. Y. Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells. FEBS Lett. 2000, 486, 291-296.
(145) Shi, Y. L.; Chen, W. Y. Effect of Toosendanin on acetylcholine level of rat brain, a microdialysis study. Brain Res. 1999, 850, 173-178.
(146) Yu, J.-C.; Min, Z.-D.; Ip, N. Y. Melia toosendan regulates PC12 Cell differentiation via the activation of protein kinase A and extracellular signal-regulated kinases. Neurosignals 2004, 13, 248-257.
(147) Cheon, E. W.; Saito, T. Choline acetyltransferase and acetylcholinesterase in the normal, developing and regenerating newt retinas. Brain Res. Dev. Brain Res. 1999, 116, 97-109.
(148) Liu, J.-H.; Bo, J.; Bao, Y.-M.; An, L.-J. Effect of Cuscuta chinensis glycoside on the neuronal differentiation of rat pheochromocytoma PC12 cells. Int. J. Dev. Neurosci. 2003, 21, 277-281.
(149) Gundimeda, U.; McNeill, T. H.; Schiffman, J. E.; Hinton, D. R.; Gopalakrishna, R. Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: Possible role of reactive oxygen species. J. Neurosci. Res. 2010, 88, 3644-3655.
(150) More, S. V.; Koppula, S.; Kim, I. S.; Kumar, H.; Kim, B. W.; Choi, D. K. The role of bioactive compounds on the promotion of neurite outgrowth. Molecules 2012, 17, 6728-6753.
(151) 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.
(152) Iwayama, Y.; Ando, H.; Ishida, H.; Kiso, M. A first total synthesis of ganglioside HLG-2. Chem. Eur. J. 2009, 15, 4637-4648.
(153) Yamamoto, T.; Teshima, T.; Saitoh, U.; Hoshi, M.; Shiba, T. Synthesis of ganglioside M5 from sea urchin egg. Tetrahedron Lett. 1994, 35, 2701-2704.
(154) Tsai, Y.-F.; Shih, C.-H.; Su, Y.-T.; Yao, C.-H.; Lian, J.-F.; Liao, C.-C.; Hsia, C. -W.; Shu, H.-A.; Rani, R. The total synthesis of a ganglioside Hp-s1 analogue possessing neuritogenic activity by chemoselective activation glycosylation. Org. Biomol. Chem. 2012, 10, 931-934.
(155) Iwayama, Y.; Ando, H.; Tanaka, H. N.; Ishida, H.; Kiso, M. Synthesis of the glycan moiety of ganglioside HPG-7 with an unusual trimer of sialic acid as the inner sugar residue. Chem.Commun. 2011, 47, 9726-9728.
(156) Tamai, H.; Ando, H.; Ishida, H.; Kiso, M. First synthesis of a pentasaccharide moiety of ganglioside GAA‑7 containing unusually modified sialic acids through the use of N-Troc-sialic acid derivative as a key unit. Org. Lett. 2012, 14, 6342-6345.
(157) Hanashima, S.; Yamaguchi, Y.; Ito, Y.; Sato, K. Synthesis of the starfish ganglioside AG2 pentasaccharide. Tetrahedron Lett. 2009, 50, 6150-6153.
(158) Xu, F. F.; Wang, Y.; Xiong, D. C.; Ye, X. S. Stereoselective Synthesis of the trisaccharide moiety of ganglioside HLG-2. J. Org. Chem. 2014, 79. 797-802.
(159) Wu, Y.-F.; Tsai, Y.-F.; Guo, J.-R.; Yu, C.-P.; Yu, H.-M.; L, C.-C. First total synthesis of ganglioside DSG-A possessing neuritogenic activity. Org. Biomol. Chem. 2014, 12, 9345-9349.
(160) Chen, W.-S.; Sawant, R. C.; Yang, S.-A.; Liao, Y.-J.; Liao, J.-W.; Badsara, S. S.; Luo, S.-Y. Synthesis of ganglioside Hp-s1. RSC Adv. 2014, 4, 47752-47761.
(161) Boons, G. J.; Demchenko, A. V. Recent advances in O-sialylation. Chem. Rev. 2000, 100, 4539-4565.
(162) Hanashima, S. Recent strategies for stereoselective sialylation and their application to the synthesis of oligosialosides. Trends Glycosci. Glycotechnol. 2011, 23, 111-121.
(163) Adak, A. K.; Yu, C.-C.; Liang, C.-F.; Lin, C.-C. Synthesis of sialic acid-containing saccharides. Curr. Opin. Chem. Biol. 2013, 17, 1030-1038.
(164) Kanie, O.; Kiso, M.; Hasegawa, A. Glycosylation using methylthioglycosides of N-acetylneuraminic acid and dimethyl(methylthio)sulfonium triflate. J. Carbohydr. Chem. 1988, 7, 501-506.
(165) Hasegawa, A.; Ohki, H.; Nagahama, T.; Ishida, H.; Kiso, M. A facile, large scale preparation of the methyl 2-thioglycoside of N-acetylneuraminic acid, and its usefulness for the α-stereoselective synthesis of sialoglycosides. Carbohydr. Res. 1991, 212, 277-281.
(166) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Nitriles as solvents in glycosylation reactions: highly selective β-glycoside synthesis. Synlett 1990, 694-696.
(167) Vankar, Y. D.; Vankar, P. S.; Behrendr, M.; Schmidt, R. R. Synthesis of -O-glycosides using enol ether and imidate derived leaving groups. Emphasis on the use of nitriles as a solvent. Tetrahedron 1991, 47, 9985-9992.
(168) Schmidt, R. R.; Rücker, E. Stereoselective glycosidations of uronic acids. Tetrahedron Lett. 1980, 21, 1421-1424.
(169) Birberg, W.; Lönn, H. Glycosylation with sialic acid at HO-3 of three different O-protected D-galactosides in acetonitrile/dichloromethane at low temperature. Tetrahedron Lett. 1991, 32, 7457-7458.
(170) Okamoto, K.; Kondo, T.; Goto, T. Syntheses of α(2-9) and α(2-8) linked neuraminylneuraminic acid derivatives. Tetrahedron Lett. 1986, 27, 5229-5232.
(171) Ito, Y.; Numata, M.; Sugimoto, M.; Ogawa, T. Highly stereoselective synthesis of ganglioside GD 3. J. Am. Chem. Soc. 1989, 111, 8501-8510.
(172) Ito, Y.; Nunomura, S.; Shibayama, S.; Ogawa, T. Studies directed toward the synthesis of polysialogangliosides: The regioand stereocontrolled synthesis of rationally designed fragments of the tetrasialoganglioside GQ l. J. Org. Chem. 1992, 57, 1821-1831.
(173) De Meo, C.; Priyadarshani, U. C-5 Modifications in N-acetyl-neuraminic acid: scope and limitations. Carbohydr. Res. 2008, 343, 1540-1552.
(174) De Meo, C.; Demchenko, A. V.; Boons, G. J. A stereoselective approach for the synthesis of α-sialosides. J. Org. Chem. 2001, 66, 5490-5497.
(175) Tanaka, H.; Nishiura, Y.; Takahashi, T. Stereoselective synthesis of oligo-α-(2,8)-sialic acids. J. Am. Chem. Soc. 2006, 128, 7124-7125.
(176) Tanaka, H.; Nishiure, Y.; Takahashi, T. An efficient convergent synthesis of GP1c ganglioside epitope. J. Am. Chem. Soc. 2008, 130, 17244-17245.
(177) De Meo, C.; Farris, M.; Ginder, N.; Gulley, B.; Priyadarshani, U. Woods, M. Solvent effect in the synthesis of sialosyl α(2–6) galactosides: Is acetonitrile the only choice? Eur. J. Org. Chem. 2008, 3673-3677.
(178) Kononov, L. O.; Malysheva, N. N.; Orlova, A. V.; Zinin, A. I.; Laptinskaya, T. V.; Kononova, E. G.; Kolotyrkina, N. G. Concentration dependence of glycosylation outcome: A clue to reproducibility and understanding the reasons behind. Eur. J. Org. Chem. 2012, 1926-1934.
(179) Okamoto, K.; Goto, T. Glycosidation of sialic acid. Tetrahedron 1990, 46, 5835-5837.
(180) Koenigs, W.; Knoor, E., On certain derivatives of glucose and galactose. Chem. Ber. 1901, 34, 957-981.
(181) Hekferich, B.; Zirner, J., For the synthesis of tetraacetyl-hexoses with free 2-hydroxyl. Synthesis of some disaccharides. Chem. Ber. 1962, 95, 2604-2611.
(182) Kanie, O.; Nakamura, J.; Kiso, M.; Hasegawa, A. Stereoselective synthesis of 5'-S-(5-acetamido-3,5-dideoxy-D-glycero-α-and-β-D-galacto-2-nonulopyranosylonic Acid)-5'-thio Cytidixe. J. Carbohydr. Chem. 1987, 6, 105-115.
(183) Byramova, N. E.; Tuzikov, A. B.; Bovin, N. V. A simple procedure for the synthesis of the methyl and benzyl glycosides of Neu5Ac and 4-epi-Neu5Ac. Conversion of the benzyl and methyl glycosides of Neu5Ac into N-trifluoroacetylneuraminic acid benzyl glycosides. Carbohydr. Res. 1992, 237, 161-175.
(184) Martin, T. J.; Schmidt, R. R. Efficient sialylation with phosphite as leaving group. Tetrahedron Lett. 1992, 33, 6123-6126.
(185) Kondo, H.; Ichikawa, Y.; Wong, C.-H. β-Sialyl phosphite and phosphoramidite: Synthesis and application to the chemoenzymatic synthesis of CMP-sialic acid and sialyl oligosaccharides. J. Am. Chem. Soc. 1992, 114, 8148-8750.
(186) Hsu, C.-H.; Chu, K.-C.; Lin, Y.-S.; Han, J.-L.; Peng, Y.-C.; Ren, C.-T.; Wu, C. -Y.; Wong, C.-H. Highly alpha-selective sialyl phosphate donors for efficient preparation of natural sialosides. Chem. Eur. J. 2010, 16, 1754-1760.
(187) Martin, T. J.; Brescello, R.; Toepfer, A.; Schmidt, R. R. Synthesis of phosphites and phosphates of neuraminic acid and their glycosyl donor properties- convenient synthesis of GM3. Glycoconjugate J. 1993, 10, 16-25.
(188) Chu, K.-C.; Ren, C.-T.; Lu, C.-P.; Hsu, C.-H.; Sun, T.-H.; Han, J.-L.; Pal, B. ; Chao, T.-A.; Lin, Y.-F.; Wu, S.-H.; Wong, C.-H.; Wu, C.-Y. Efficient and stereoselective synthesis of (2-9) oligosialic acids: From monomers to dodecamers. Angew. Chem., Int. Ed. 2011, 50, 9391-9395.
(189) Roy, R.; Andersson, F. O.; Letellier, M., "Active" and "latent" thioglycosyl donors in oligosaccharide synthesis. Application to the synthesis of α-sialosides. Tetrahedron Lett. 1992, 33, 6053-6056.
(190) Crich, D.; Li, W. -Selective sialylations at -78 oC in nitrile solvents with a 1-adamantanyl thiosialoside. J. Org. Chem. 2007, 72, 7794 -7797.
(191) De Meo, C.; Parker, O. Thiomidoyl approach to the synthesis of -sialosides. Tetrahedron: Asymmetry 2005, 16, 303-307.
(192) Cai, S.; Yu, B., Efficient sialylation with phenyltrifluoroacetimidates as leaving groups. Org. Lett. 2003, 5, 3827-3830.
(193) Lin, C.-C.; Huang, K.-T.; Lin, C.-C. N-Trifluoroacetyl sialyl phosphite donors for the synthesis of (2→9) oligosialic acids. Org. Lett. 2005, 7, 4169-4172.
(194) Hasegawa, A.; Nagahama, T.; Ohki, H.; Hotta, K.; Ishida, H.; Kiso, M. Communication: Synthetic studies on sialoglycoconjugates: Reactivity of glycosyl promoters in α-glycosylation of N-acetyl-neuraminic acid with the primary and secondary hydroxyl groups in the suitably protected galactose and lactose derivatives. J. Carbohydr. Chem. 1991, 10, 493-498.
(195) Lahmann, M.; Oscarson, S. Investigation of the reactivity difference between thioglycoside donors with variant aglycon parts. Can. J. Chem. 2002, 80, 889-893.
(196) Gu, Z. Y.; Zhang, J. X.; Xing, G. W. N-Acetyl-5-N,4-O-oxazolidinone- protected sialyl sulfoxide: an -selective sialyl donor with Tf2O/(Tol)2SO in dichloromethane. 2012, 7, 1524-1528.
(197) Demchenko, A. V.; Boons, G. J. A novel and versatile glycosyl donor for the preparation of glycosides of N-acetyineuraminic acid. Tetrahedron Lett. 1998, 39, 3065-3068.
(198) Crich, D.; Li, W.-J. Efficient glycosidation of a phenyl thiosialoside donor with diphenyl sulfoxide and triflic anhydride in dichloromethane. Org. Lett. 2006, 8, 959-962.
(199) Schneider, R.; Freyhardt, C. C.; Schmidt, R. R. 5-Azido derivatives of neuraminic acid - Synthesis and structure. Eur. J. Org. Chem. 2001, 1655-1661.
(200) 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 -glycosylation of primary hydroxy groups. Angew. Chem., Int. Ed. 2001, 40, 2900-2903.
(201) De Meo. C.; Demchenko, A. V.; Boons, G. J. Trifluoroacetamido substituted sialyl donors for the preparation of sialyl galactosides. Aust. J. Chem. 2002, 55, 131-134.
(202) Pan, Y.-B.; Chefalo, P.; Nagy, N.; Harding, C.; Guo, Z.-G. Synthesis and immunological properties of N-modified GM3 antigens as therapeutic cancer vaccines. J. Med. Chem. 2005, 48, 875-883.
(203) Ando, H.; Koike, Y.; Ishida, H.; Kiso, M. Extending the possibility of an N-Troc-protected sialic acid donor toward variant sialo-glycoside synthesis. Tetrahedron Lett. 2003, 44, 6883- 6886.
(204) Adachi, M.; Tanaka, H.; Takahashi, T. An effective sialylation method using N-Troc- and N-Fmoc-protected β-thiophenyl sialosides and application to the one-pot two-step synthesis of 2,6-sialyl-T antigen. Synlett 2004, 609-614.
(205) Tanaka, H.; Adachi, M.; Takahashi, T. One-pot synthesis of sialo-containing glycosyl amino acids by use of an N-trichloroethoxycarbonyl--thiophenyl sialoside. Chem. Eur. J. 2005, 11, 849-862.
(206) Tanaka, K.; Goi, T.; Fukase K. Highly efficient sialylation towards (2-3)- and (2-6)-Neu5Ac-Gal synthesis: significant ‘fixed dipole effect’ of N-phthalyl group on -selectivity. Synlett 2005, 2958-2962.
(207) Tanaka, S.; Goi, T.; Tanaka, K.; Fukase, K. Highly efficient -sialylation by virtue of fixed dipole effects of N-phthalyl group: application to continuous flow synthesis of (2-3)-and (2-6)-Neu5Ac-Gal motifs by microreactor. J. Carbohydr. Chem. 2007, 26, 369-394.
(208) Farris, M. D.; De Meo, C. Application of 4,5-O,N-oxazolidinone protected thiophenyl sialosyl donor to the synthesis of α-sialosides. Tetrahedron Lett. 2007, 48, 1225-1227.
(209) Lin, C.-C.; Lin, N.-P.; Sahabuddin, L. S.; Reddy, V. R.; Huang, L.-D.; Hwang, K.-C.; Lin, C.-C. 5-N,4-O-Carbonyl-7,8,9-tri-O-chloroacetyl-protected sialyl donor for the stereoselective synthesis of -(29)-tetrasialic acid. J. Org. Chem. 2010, 75, 4921-4928.
(210) Tanaka, H.; Nishiura, Y.; Takahashi, T. Stereoselective synthesis of α(2,9) di-to tetrasialic acids, using a 5,4-N,O-carbonyl protected thiosialoside. J. Org. Chem. 2009, 74, 4383-4386.
(211) Crich, D.; Wu, B.-L. Stereoselective iterative one-pot synthesis of N-glycolyl- neuraminic acid-containing oligosaccharides. Org. Lett. 2008, 10, 4033-4035.
(212) Crich, D.; Li, W.-J. O-Sialylation with N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donors in dichloromethane: Facile and selective cleavage of the oxazolidinone ring. J. Org. Chem. 2007, 72, 2387-2391.
(213) Mandhapati, A. R.; Rajender, S.; Shaw, J.; Crich, D. The isothiocyanato moiety: an ideal protecting group for the stereoselective synthesis of sialic acid glycosides and subsequent diversification. Angew. Chem., Int. Ed. 2015, 54, 1275-1278.
(214) 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.
(215) Plante, O. J.; Palmacci, E. R.; Andrade, R. B.; Seeberger, P. H. Oligosaccharide synthesis with glycosyl phosphate and dithiophosphate triesters as glycosylating agents. J. Am. Chem. Soc. 2001, 123, 9545-9554.
(216) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. “Armed” and “disarmed” n-pentenyl glycosides in saccharide couplings leading to oligosaccharides. J. Am. Chem. Soc. 1988, 110, 5583-5584;
(217) Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottoson, H. Armed/disarmed effects in glycosyl donors: rationalization and sidetracking. J. Org. Chem. 1990, 55, 6068-6070.
(218) Raghavan, S.; Kahne, D. A. A one-step synthesis of the ciclamycin trisaccharide. J. Am. Chem. Soc. 1993, 115, 1580-1581.
(219) Nguyen, H. M.; Poole, J. L.; Gin, D. Y. Chemoselective iterative dehydrative glycosylation. Angew. Chem., Int. Ed. 2001, 40, 414-417.
(220) Yamago, S.; Yamada, T.; Maruyama, T.; Yoshida, J. I. Iterative glycosylation of 2-deoxy-2-aminothioglycosides and its application to the combinatorial synthesis of linear oligoglucosamines. Angew. Chem., Int. Ed. 2004, 43, 2145-2148.
(221) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Iterative one-pot synthesis of oligosaccharides. Angew. Chem., Int. Ed. 2004, 43, 5221-5224.
(222) Kanie, O.; Ito, Y.; Ogawa, T. Orthogonal glycosylation strategy in oligosaccharide synthesis. J. Am. Chem. Soc. 1994, 116, 12073-12074.
(223) 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.
(224) Demchenko, A. V.; De Meo, C. Semi-orthogonality of O-pentenyl and S-ethyl glycosides: application for the oligosaccharide synthesis. Tetrahedron Lett. 2002, 43, 8819-8822.
(225) Kaeothip, S.; Pornsuriya-sak, P.; Rath, N. P.; Demchenko, A. V. Unexpected orthogonality of S-benzoxazolyl and S-thiazolinyl glycosides: application to expeditious oligosaccharide assembly. Org. Lett. 2009, 11, 799-802.
(226) Seeberger, P. H.; Haase, W. C. Solid-phase oligosaccharide synthesis and combinatorial carbohydrate libraries. Chem. Rev. 2000, 100, 4349-4393.
(227) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Automated solid-phase synthesis of oligosaccharides. Science 2001, 291, 1523-1527.
(228) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischant, R.; Baasov, T.; Wong, C.-H. Programmable one-pot oligosaccharide synthesis. J. Am. Chem. Soc. 1999, 121,734-753.
(229) Koeller, K. M.; Wong, C.-H. Synthesis of complex carbohydrates and glycoconjugates: Enzyme-based and programmable one-pot strategies. Chem. Rev. 2000, 100, 4465-4493.
(230) Lee, J.-C.; Greenberg, W. A.; Wong, C.-H. Programmable reactivity-based one- pot oligosaccharide synthesis. Nat. Protoc. 2007, 1, 3143-3152.
(231) Liu, H.-W.; Nakanishi, K. Pyranose benzoates. An additivity relation in the amplitudes of exciton-split CD curves. J. Am. Chem. Soc. 1982, 104, 1178-1185.
(232) Chan, L.; Taylor, M. S. Regioselective alkylation of carbohydrate derivatives catalyzed by a diarylborinic acid derivative. Org. Lett. 2011, 13, 3090-3093.
(233) Lee, D.; Taylor, M. S. Borinic acid-catalyzed regioselective acylation of carbohydrate derivatives. J. Am. Chem. Soc. 2011, 133, 3724-3727.
(234) Yang, W.; Mortier, W. J. The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines. J. Am. Chem. Soc. 1986, 108, 5708-5711.
(235) Ogura, H., Sialic acids derivatives as glycolipoids. In Carbohydrates: Synthetic Methods and Application in Medicinal Chemistry, Ogura, H.; Hasegawa, A.; Suami, T. (Eds.), John Wiley & Sons, New York, 1992, pp. 282-303.
(236) Hori, H.; Nakajuma, T.; Nishida, Y.; Ohrui, H.; Meguro, H., A simple method to determine the anomeric configuration of sialic acid and its derivatives by 13C-NMR. Tetrahedron Lett. 1988, 29, 6317-6320.
(237) Lin, C.-C.; Adak, A. K.; Horng, J.-C.; Lin, C.-C. Phosphite-based sialic acid donors in the synthesis of (2→9) oligosialic acids. Tetrahedron 2009, 65, 4714-4725.
(238) Pedersen, C. M.; Nordstrøm, L. U.; Bols, M.“Super armed” glycosyl donors: conformational arming of thioglycosides by silylation. J. Am. Chem. Soc. 2007, 129, 9222-9235.
(239) Hsu, Y.; Lu, X.-A.; Zulueta, M. M. L.; Tsai, C.-M.; Lin, K.-I.; Hung, S.-C.; Wong, C.-H. Acyl and silyl group effects in reactivity-based one-pot glycosylation: synthesis of embryonic stem cell surface carbohydrates Lc4 and IV2Fuc-Lc4. J. Am. Chem. Soc. 2012, 134, 4549-4552.
(240) Mulard, L. A.; Kovac, P.; Glaudemans, C. P. J. Synthesis of methyl O--L-rhamnopyranosyl-(1→2)--galactopyranosides specifically deoxy- genated at position 3, 4, or 6 of the galactose residue. Carbohydr. Res. 1994, 251, 213-232.
(241) Sherman, A. A.; Mironov, Y. V.; Yudina, O. N. Nifantiev, N. E. The presence of water improves reductive openings of benzylidene acetals with trimethylaminoborane and aluminium chloride. Carbohydr. Res. 2003, 338, 697-703.
(242) Sun, B.; Jiang, H. Pre-activation based, highly alpha-selective O-sialylation with N-acetyl-5, N, 4, O-carbonyl-protected p-tolyl thiosialoside donor. Tetrahedron Lett. 2011, 52, 6035-6038.
(243) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J. L. Efficient and highly selective oxidation of primary alcohols to aldehydes by N-chlorosuccinimide mediated by oxoammonium salts. J. Org. Chem. 1996, 61, 7452-7454.
(244) Dere, R. T.; Wang, Y.; Zhu, X. A direct and stereospecific approach to the synthesis of α-glycosyl thiols. Org. Biomol. Chem. 2008, 6, 2061-2063.
(245) Lee, J.-C.; Chang, S.-W.; Liao, C.-C.; Chi, F.-C.; Chen, C.-S.; Wen, Y.-S.; Wang, C.-C.; Kulkarni, S. S.; Puranik, R.; Liu, Y.-H.; Hung, S.-C. From D-glucose to biologically potent L-hexose derivatives: synthesis of α-L-iduronidase fluorogenic detector and the disaccharide moieties of bleomycin A2 and heparan sulfate. Chem. Eur. J. 2004, 10, 399-415.
(246) Stichler-Bonaparte, J.; Bernet, B.; Vasella, A. Oligosaccharide analogues of polysaccharides Part 25. Helv. Chim. Acta 2002, 85, 2235-2257.
(247) Zottola, M. A.; Alonso, R.; Vite, G. D.; Fraser-Reid, B. A practical, efficient large-scale synthesis of 1,6-anhydrohexopyranoses. J. Org. Chem. 1989, 54, 6123-6125.
(248) Caron, S.; McDonald, A. I.; Heathcock, C. H. Synthesis of 1-substituted and 1,4-disubstituted 2,3-di-O-benzyl-1,6-anhydrogalactofuranoses. J. Org. Chem. 1995, 60, 2780-2785.
(249) Ko, Y.-C.; Tsai, C.-F.; Wang, C.-C.; Dhurandhare, V. M.; Hu, P.-L.; Su, T.-Y.; Lico, L. S.; Zulueta, M. M. L.; Hung, S.-C. Microwave-assisted one-pot synthesis of 1,6-anhydrosugars and orthogonally protected thioglycosides. J. Am. Chem. Soc. 2014, 136, 14425-14431.
(250) Miranda, P. O.; Brouard, I.; Padron, J. I.; Bermejo, J. Ferric chloride: a mild and versatile reagent for the formation of 1,6-anhydro glucopyranoses. Tetrahedron Lett. 2003, 44, 3931-3934.
(251) Tanaka, T.; Huang, W.-C.; Noguchi, M.; Kobayashi, A.; Shoda, S. Direct synthesis of 1,6-anhydro sugars from unprotected glycopyranoses by using 2-chloro-1,3-dimethylimidazolinium chloride. Tetrahedron Lett. 2009, 50, 2154 -2157.
(252) Marra, A.; Sinaÿ, P. Stereoselective synthesis of 2-thioglycosides of N-acetyl- neuraminic acid. Carbohydr. Res. 1989, 187, 35-42.
(253) Zhu, X.; Dere, R. T.; Jiang, J.; Zhang, L.; Wang, X. Synthesis of α-glycosyl thiols by stereospecific ring-opening of 1,6-anhydrosugars. J. Org. Chem. 2011, 76, 10187-10197.
(254) Zottola, M.; Rao, B. V.; Fraser-Reid, B. A mild procedure for cleavage of 1,6-anhydro sugars. J. Chem. Soc., Chem. Commun. 1991, 14, 969-970.
(255) Chen, M.-Y.; Patkar, L. N.; Lu, K.-C.; Lee, A. S.-Y.; Lin, C.-C. Chemoselective deprotection of acid labile primary hydroxyl-protecting groups under CBr4-photoirradiation condition. Tetrahedron 2004, 60, 11465-11475.

第四章、附錄