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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁碧惠 | - |
| dc.contributor.author | Yin-Jen Lu | en |
| dc.contributor.author | 盧膺仁 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:15:33Z | - |
| dc.date.available | 2018-09-24 | - |
| dc.date.copyright | 2013-09-24 | - |
| dc.date.issued | 2013 | - |
| dc.date.submitted | 2013-08-19 | - |
| dc.identifier.citation | 第五章 參考文獻
1. Witczak, Z. J.; Nieforth, K. A. Carbohydrates in drug design, New York, Marcel Dekker 1997 2. Russell, R. J.; Kerry, P. S.; Stevens, D. J.; Steinhauer, D. A.; Martin, S. R.; Gamblin, S. J.; Skehel, J. J. Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc. Natl. Acad. Sci. USA 2008, 195, 17736-17741. 3. Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong, C.-H. Synthesis of the Globo H hexasaccharide using the programmable reactivity-based one-pot strategy. Angew. Chem. In. Ed. 2001, 40, 1274-1277. 4. Bertozzi, C. R. Chemical glycobiology. Science 2001, 291, 2357-2364. 5. Koenigs, W.; Knorr, E., Ueber einige derivate des traubenzuckers und der galactose. Ber. Der. Deutsch. Chem. Ges. 1901, 34, 957-981. 6. (a) Codee, J. D. C.; Litjens, R. E. J. N.; van den Bos, L. J.; Overkleeft, H. S.; van der Marel, G. A. Thioglycosides in sequential glycosylation strategies. Chem. Soc. Rev. 2005, 34, 769-782; (b) Garegg, P. J. Thioglycosides as glycosyl donors in oligosaccharide synthesis. Adv. Carbohyr. Chem. Biochem. 1997, 52, 179-205. 7. Schmidt, R. R.; Michel, J. Facile synthesis of α- and β-O-glycosyl imidates; preparation of glycosides and disaccharides. Angew. Chem. Int. Ed. Engl. 1980, 19, 731-732. 8. Reist, E. J.; Cruse, S. H. Neighboring group participation in carbohydrates. synthesis of 2,3-diamino-2,3-dideoxy-L-ribose. J. Org. Chem. 1969, 34, 3029-3032. 9. (a) Winstein, S.; Grunwald, E. The role of neighboring groups in replacement reactions. XIII.1 general theory of neighboring groups and reactivity. J. Am. Chem. Soc. 1948, 70, 828-837; (b) Winstein, S.; Grunwald, E.; Buckles, R. E.; Hanson, C. The role of neighboring groups in replacement reactions. XI. some reactivities involving neighboring groups1. J. Am. Chem. Soc. 1948, 70, 816-821. 10. Whitfield, D. M.; Douglas, S. P.; Tang, T.-H.; Csizmadia, I. G.; Pang, H. Y. S.; Moolten, F. L.; Krepinsky, J. J. Differential reactivity of carbohydrate hydroxyls in glycosylations. II. The likely role of intramolecular hydrogen bonding on glycosylation reactions. galactosylation of nucleoside 5′-hydroxyls for the syntheses of novel potential anticancer agents. Can. J. Chem. 1994, 72, 2225-2238. 11. (a) Lichtenthaler, Frieder W.; Oberthur, M.; Peters, S. Directed and efficient syntheses of β(1→4)-linked galacto-oligosaccharides. Eur. J. Org. Chem. 2001, 20, 3849-3869; (b) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Danishefsky, S. J. Coupling of glycal derived thioethyl glycosyl donors with glycal acceptors. an advance in the scope of the glycal assembly. J. Am. Chem. Soc. 1997, 119, 10064-10072; (c) Ye, X.-S.; Wong, C.-H. Anomeric reactivity-based one-pot oligosaccharide synthesis: a rapid route to oligosaccharide Llibraries. J. Org. Chem. 2000, 65, 2410-2431. 12. Thompson, M. J.; Hutchinson, E. J.; Stratford, T. H.; Bowler, W. B.; Blackburn, G. M. Sugar conjugates of fulvestrant (ICI 182,780): efficient general procedures for glycosylation of the fulvestrant core. Tetrahedron Lett. 2004, 45, 1207-1210. 13. Yamada, T.; Takemura, K.; Yoshida, J.-i.; Yamago, S. Dialkylphosphates as stereodirecting protecting groups in oligosaccharide synthesis. Angew. Chem. 2006, 118, 7737-7740. 14. Smoot, J. T.; Pornsuriyasak, P.; Demchenko, A. V. Development of an arming participating group for stereoselective glycosylation and chemoselective oligosaccharide synthesis. Angew. Chem. In. Ed. 2005, 44, 7123-7126. 15. Kim, J.-H.; Yang, H.; Boons, G.-J. Stereoselective glycosylation reactions with chiral auxiliaries. Angew. Chem. In. Ed. 2005, 44, 947-949. 16. (a) Andersson, F.; Fugedi, P.; Garegg, P. J.; Nashed, M. Synthesis of 1,2-cis-linked glycosides using dimethyl(methylthio) sulfonium triplate as promoter and thioglycosides as glycosyl donors. Tetrahedron Lett. 1986, 27, 3919-3922; (b) Chenault, H. K.; Castro, A.; Chafin, L. F.; Yang, J. The chemistry of isopropenyl glycopyranosides. transglycosylations and other reactions. J. Org. Chem. 1996, 61, 5024-5031; (c) Dohi, H.; Nishida, Y.; Tanaka, H.; Kobayashi, K. o-Methoxycarbonylphenyl 1-thio-β-d-galactopyranoside, a non-malodorous thio glycosylation donor for the synthesis of globosyl α (1-4)-Linkages. Synlett. 2001, 09, 1446-1448; (d) Nishizawa, M.; Shimomoto, W.; Momii, F.; Yamada, H. Stereoselective thermal glycosylation of 2-deoxy-2-acetoamino-3,4,6-tri-O-acetyl-α- D-glucopyranosyl chloride. Tetrahedron Lett. 1992, 33, 1907-1908; (e) Wegmann, B.; Schmidt, R. R. The application of the trichloroacetimidate method to the synthesis of α-D-gluco- and α-D-galactopyranosides. J. Carbohydr. Chem. 1987, 6, 357-375; (f) Shimizu, H.; Ito, Y.; Ogawa, T. PeSeNPhth-TMSOTf as a promotor of thioglycoside. Synlett. 1994, 07, 535-536. 17. (a) Adinolfi, M.; Iadonisi, A.; Ravida, A. Tunable activation of glycosyl trichloro- and (N-phenyl)trifluoro-acetimidates with Ytterbium(III) triflate: one-pot synthesis of -trisaccharides under catalytic conditions. Synlett. 2006, 04, 0583-0586; (b) Fukase, K.; Hasuoka, A.; Kinoshita, I.; Aoki, Y.; Kusumoto, S. A stereoselective glycosidation using thioglycosides, activation by combination of N-bromosuccinimide and strong acid salts. Tetrahedron 1995, 51, 4923-4932; (c) Manabe, S.; Ito, Y.; Ogawa, T. Solvent effect in glycosylation reaction on polymer support. Synlett. 1998, 06, 628-630. 18. Mukaiyama, T.; Matsubara, K. Stereoselective glycosylation reaction starting from 1-O-trimethylsilyl sugars by using diphenyltin sulfide and a catalytic amount of active acidic species. Chem. Lett. 1992, 21, 1041-1044. 19. Sasaki, M.; Gama, Y.; Yasumoto, M.; Ishigami, Y. Glycosylation reaction under high pressure. Tetrahedron Lett. 1990, 31, 6549-6552. 20. Chao, C. S.; Li, C. W.; Chen, M. C.; Chang, S. S.; Mong, K. K. Low-concentration 1,2-trans beta-selective glycosylation strategy and its applications in oligosaccharide synthesis. Chem. Eur. J. 2009, 15, 10972-10982. 21. Mensah, E. A.; Azzarelli, J. M.; Nguyen, H. M. Palladium-controlled β-selective glycosylation in the absence of the C(2)-ester participatory group. J. Org. Chem. 2009, 74, 1650-1657. 22. Sato, K.-i.; Sakai, K.; Tsushima, K.; Akai, S. The first total synthesis of telephiose A. Tetrahedron Lett. 2007, 48, 3745-3748. 23. Ohara, K.; Lin, C.-C.; Yang, P.-J.; Hung, W.-T.; Yang, W.-B.; Cheng, T.-J. R.; Fang, J.-M.; Wong, C.-H. Synthesis and bioactivity of β-(1→4)-linked oligomannoses and partially acetylated derivatives. J. Org. Chem. 2013, 78, 6490-6411. 24. Bouveng, H. O. Phenylisocyanate derivatives of carbohydrates. II. location of the O-acetyl groups in birch xylan. Acta. Chem. Scan. 1961, 15, 96-100. 25. Plusquellec, D.; Lefeuvre, M. Sugar chemistry without protecting groups: a regioselective addition of the primary hydroxyl of monosaccharides to alkylisocyanates. Tetrahedron Lett. 1987, 28, 4165-4168. 26. Pirkle, W. H.; Hauske, J. R. Trichlorosilane induced cleavage. a mild method for retrieving carbinols from carbamates. J. Org. Chem. 1977, 42, 2781-2782. 27. Akai, S.; Nishino, N.; Iwata, Y.; Hiyama, J.-i.; Kawashima, E.; Sato, K.-i.; Ishido, Y. Tetrabutylammonium nitrite - acetic anhydride system, tetrabutylammonium nitrite, tetrabutylammonium acetate, and cesium acetate - 18-crown-6 for efficient unmasking of alkyl N-phenylcarbamates. Tetrahedron Lett. 1998, 39, 5583-5586. 28. Kojima, M.; Nakamura, Y.; Nakamura, A.; Takeuchi, S. Total synthesis of cucurbitoside A using a novel fluorous protecting group. Tetrahedron Lett. 2009, 50, 939-942. 29. Sato, K.-I.; Sakai, K.; Kojima, M.; Akai, S. The use of 2-O-propagyloxycarbonyl protecting group in the selective formation of 1,2-trans-glycosidic linkage. Tetrahedron Lett. 2007, 48, 4423-4425. 30. Li, H.; Wen, M.; Wang, Z.-X. Computational mechanistic study of the hydrogenation of carbonate to methanol catalyzed by the RuIIPNN complex. Inorg. Chem. 2012, 51, 5716-5727. 31. Koketsu, M.; Kuwahara, M.; Sakurai, H.; Ishihara, H. First synthesis of a trisaccharide of glycosylkaemferide: a resistance factor in carnations. Synth. Commun. 2004, 34, 239-245. 32. Agarwal, K. L.; Khorana, H. G. Polynucleotides. CII. use of aromatic isocyanates for selective blocking of the therminal 3'-hydroxyl group in protected deoxyribooligonucleotides. J. Am. Chem. Soc. 1972, 94, 3578-3585. 33. Duggan, M. E.; Imagire, J. S. Copper(I) chloride catalyzed addition of alcohols to alkyl isocyanates. a mild and expedient method for alkyl carbamate formation. Synthesis 1989, 02, 131-132. 34. Fraser-Reid, B.; Wu, Z.; Andrews, C. W.; Skowronski, E.; Bowen, J. P. Torsional effects in glycoside reactivity: saccharide couplings mediated by acetal protecting groups. J. Am. Chem. Soc. 1991, 113, 1434-1435. 35. Takeuchi, K.; Tamura, T.; Jona, H.; Mukaiyama, T. A novel activating agents of disarmed thioglycosides, combination of trityl tetrakis(pentafluorophenyl)borate, iodine and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). Chem. Lett. 2000, 29, 692-693. 36. Ercegovic, T.; Meijer, A.; Magnusson, G.; Ellervik, U. Iodine monochloride/ silver trifluoromethanesulfonate (ICl/AgOTf) as a convenient promoter system for O-glycoside synthesis. Org. Lett. 2001, 3, 913-915. 37. Adinolfi, M.; Iadonisi, A.; Ravida, A.; Valerio, S. Remarkably efficient activation of glycosyl trichloro- and (N-phenyl)trifluoroacetimidates with bismuth(III) triflate. Tetrahedron Lett. 2006, 47, 2595-2599. 38. (a) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Efficient activation of glycosyl N-(phenyl)trifluoroacetimidate donors with ytterbium(III) triflate in the glycosylation reaction. Tetrahedron Lett. 2002, 43, 5573-5577; (b) Adinolfi, M.; Iadonisi, A.; Ravida, A.; Schiattarella, M. Moisture stable promoters for selective α-fucosylation reactions: synthesis of antigen fragments. Synlett 2004, 2, 0275-0278. 39. Crasto, C. F.; Jones, G. B. A practical method for preparation of β-glycosides of N-acetylglucosamine. Tetrahedron Lett. 2004, 45, 4891-4894. 40. (a) Kollar, R.; Reinhold, B. B.; Petrakova, E.; Yeh, H. J. C.; Ashwell, G.; Drgonova, J.; Kapteyn, J. C.; Klis, F. M.; Cabib, E. architecture of the yeast cell wall: β(1→6)-glucan interconnects monnoprotein, β(1→3)-glucan, and chitin. J. Biol. Chem. 1997, 272, 17762-17775; (b) Shahinian, S.; Bussey, H., β-1,6-glucan synthesis in Saccharomyces cerevisiae. Mol. Microbiol. 2000, 35, 477-489. 41. (a) Arungundram, S.; Al-Mafraji, K.; Asong, J.; Leach, F. E.; Amster, I. J.; Venot, A.; Turnbull, J. E.; Boons, G.-J. Modular synthesis of heparan sulfate oligosaccharides for structure−activity relationship studies. J. Am. Chem. Soc. 2009, 131, 17394-17405; (b) Prabhu, A.; Venot, A.; Boons, G.-J. New set of orthogonal protecting groups for the modular synthesis of heparan sulfate fragments. Org. Lett. 2003, 5, 4975-4978; (c) Zong, C.; Venot, A.; Dhamale, O.; Boons, G.-J. Fluorous supported modular synthesis of heparan sulfate oligosaccharides. Org. Lett. 2013, 15, 342-345. 42. Crich, D.; Dai, Z.; Gastaldi, S. On the role of neighboring group participation and ortho esters in β-xylosylation: 13C NMR observation of a bridging 2-phenyl- 1,3-dioxalenium ion. J. Org. Chem. 1999, 64, 5224-5229. 43. Zeng, Y.; Wang, Z.; Whitfield, D.; Huang, X. Installation of electron-donating protective groups, a strategy for glycosylating unreactive thioglycosyl acceptors using the preactivation-based glycosylation method. J. Org. Chem. 2008, 73, 7952-7962. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60323 | - |
| dc.description.abstract | 在合成寡醣分子中，醣基化反應的位向選擇性是非常重要的，鄰基效應一般常用於建立具有高度選擇性的1,2-反式醣苷鍵；然而，常用於鄰基效應的酯基卻很容易在鹼性的條件下被去除，因此在合成複雜的多醣類的時候限制了酯基的應用性。
在本研究當中，我們建立一個新的保護基團：2-O-N-benzylcarbamate應用於建立良好位向選擇性的醣基化反應，我們利用2-O-N-benzylcarbamate來合成雙醣以及常見於酵母菌細胞壁上的組成：β-(1→6)-glucan。由於當醣受體的立體障礙愈加明顯時，帶有2-O-N-benzylcarbamate的醣受體便無法順利與之進行醣基化反應 (通常只有極微量的產物或沒有反應)，為了瞭解這樣的現象，我們使用核磁共振 (NMR)來捕捉64所產生的中間產物，發現了C-1帶有三氟甲磺酸基團的化合物107，這個反應性較差的中間體可能解釋了這個保護基在與立體障礙較大的葡萄醣四號位置的限制性。 N-benzylcarbamoyl 基團可以利用四丁基亞硝酸銨來進行選擇性去保護而不影響其他如：酯基、醚基以及醚硫基等保護基團，且N-benzylcarbamoyl 基團能夠忍受較為極端的條件而不受影響，這樣的特性使得N-benzylcarbamoyl 基團可以做為一個二號位置的保護基來達到良好1,2-反式醣苷鍵的結果。 | zh_TW |
| dc.description.abstract | Stereoselective glycosylation is fundamentally important for the synthesis of oligosaccharide. Neighboring-participating of 2-O-carboxylate ester is responsible for the facile and highly stereoselective synthesis of 1,2-trans class of glycosidic bonds. However, the property of base-labile of ester might limit its application in the synthesis of complex oligosaccharide that requires delicate protective group manipulations.
In this study, 2-O-N-benzylcarbamate was introduced as a new protecting group for β–selective glycosylation. Our results exemplified the utility of 2-O-N-benzylcarbamate in the construction of disaccharide and naturally occurring yeast cell wall component: β-(1→6)-glucan. The steric hindrance glycosyl acceptors encountered with the problem of low yield (or no reaction) when they were glycosylated with 2-O-N-benzylcarbamate glycosyl donor. To understand the mechanism of this reaction, nuclear magnetic resonance (NMR) was applied to trap the activated intermediate of compound 64. The less reactivity of 1-OTf-intermediate 107 was detected which might explain the limitation of this protecting group in the glycosylation with the very sterically demanding glucose 4-OH acceptors. N-Benzylcarbamoyl group can be selective removed by tetrabutylammonium nitrite without affecting other groups, such as ester, ether, and thiol ether groups and can be also retained under harsh deprotection processes. These highly selective properties made N-benzylcarbamoyl a unique and useful protecting group for 2-O-position of glycosyl donor for 1,2-trans-glycosylation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:15:33Z (GMT). No. of bitstreams: 1
ntu-102-R00423004-1.pdf: 11504677 bytes, checksum: b9f761c63509653d569913fcc0a0a5ca (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 目錄
口試委員審定書 i 謝辭 iii 中文摘要 v Abstract vii 目錄 ix 圖目錄 xi 表目錄 xii 路徑目錄 xiii 縮寫表 xiv 第一章 研究背景 1 1.1. 醣分子在生物體中扮演的角色 1 1.2. 醣類立體化學 3 1.3. 醣基化的方法 4 1.4. 鄰基效應 6 1.5. 利用非鄰基效應得到1,2-反式醣苷鍵的方法 10 1.6. 針對天然物的合成需要特別關注1,2-trans glycosylation的分子 11 1.7. 苄氨基甲酯的應用 13 1.8. 研究動機與目的 15 第二章 結果與討論 18 2.1. 醣基化反應條件篩選與優化 18 2.2. 苄胺基甲酸酯於醣基化反應之應用 22 2.3. 選擇性去除保護的方法與嘗試 26 2.4. 苄胺基甲酸酯於醣基化反應的應用 28 2.5. 以苄胺基甲酸酯應用於Fondaparinux的嘗試 30 2.6. 使用核磁共振觀察苄胺基甲酸酯對於醣基化反應中間體的影響 32 2.7. 以胺基甲酸酯為二號位置保護基的限制與改進的方法 36 第三章 結論 38 第四章 實驗部分 39 4.1. 一般實驗方法 39 4.2. 實驗試劑及儀器來源 39 4.3. 合成步驟及數據 42 第五章 參考文獻 69 第六章 附圖 74 | - |
| dc.language.iso | zh-TW | - |
| dc.subject | 苄 | zh_TW |
| dc.subject | 胺基甲酸酯 | zh_TW |
| dc.subject | 鍵 | zh_TW |
| dc.subject | 2-β反式醣苷 | zh_TW |
| dc.subject | β-Selective Glycosylation | en |
| dc.subject | 2-O-N-Benzylcarbamate | en |
| dc.title | 利用苄胺基甲酸酯做為新穎之保護基並建構1,2-β反式醣苷鍵與其應用於多醣合成之研究 | zh_TW |
| dc.title | 2-O-N-Benzylcarbamate Promoted β-Selective Glycosylation and Its Applications in the Stereoselective Synthesis of Oligosaccharides | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 101-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 李水盛,顧記華,蒙國光,鄭偉杰 | - |
| dc.subject.keyword | 苄,胺基甲酸酯,1,2-β反式醣苷,鍵, | zh_TW |
| dc.subject.keyword | 2-O-N-Benzylcarbamate,β-Selective Glycosylation, | en |
| dc.relation.page | 111 | - |
| dc.rights.note | 有償授權 | - |
| dc.date.accepted | 2013-08-19 | - |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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