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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 方俊民(Jim-Min Fang) | |
dc.contributor.author | Chia-Chin Cho | en |
dc.contributor.author | 卓佳慶 | zh_TW |
dc.date.accessioned | 2021-06-15T02:25:20Z | - |
dc.date.available | 2011-08-20 | |
dc.date.copyright | 2009-08-20 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-08-17 | |
dc.identifier.citation | (1) Mowry, D. T. The preparation of nitriles. Chem. Rev. 1948, 42, 189–283.
(2) Smith, M. B. Compendium of Organic Synthetic Methods; Wiley: New York, 2001; pp 100-116. (3) Gunanathan, C.; Ben-David, Y.; Milstein, D. Direct synthesis of amides from alcohols and amines with liberation of H-2. Science 2007, 317, 790–792. (4) Togo, H.; Iida, S. Synthetic use of molecular iodine for organic synthesis. Synlett 2006, 2159–2175. (5) Ekoue-Kovi, K.; Wolf, C. One-pot oxidative esterification and amidation of aldehydes. Chem. Eur. J. 2008, 14, 6302–6315. (6) Bode, J. W.; Fox, R. M.; Baucom, K. D. Chemoselective amide ligations by decarboxylative condensations of N-alkylhydroxylamines and alpha-ketoacids. Angew. Chem., Int. Ed. 2006, 45, 1248–1252. (7) Nakagawa, K.; Onoue, H.; Minami, K. Oxidation with nickel peroxide. a new synthesis of amides from aldehydes or alcohols. Chem. Commun. 1966, 17–18. (8) Tamaru, Y.; Yamada, Y.; Yoshida, Z. Direct oxidative transformation of aldehydes to amides by palladium catalysis. Synthesis 1983, 474–476. (9) Suto, Y.; Yamagiwa, N.; Torisawa, Y. Pd-catalyzed oxidative amidation of aldehydes with hydrogen peroxide. Tetrahedron Lett. 2008, 49, 5732–5735. (10) Naota, T.; Murahashi, S. I. Ruthenium-catalyzed transformations of amino-alcohols to lactams. Synlett 1991, 693–694. (11) Nordstrom, L. U.; Vogt, H.; Madsen, R. Amide synthesis from alcohols and amines by the extrusion of dihydrogen. J. Am. Chem. Soc. 2008, 130, 17672–17673. (12) Tillack, A.; Rudloff, I.; Beller, M. Catalytic amination of aldehydes to amides. Eur. J. Org. Chem. 2001, 523–528. (13) Fujita, K.; Takahashi, Y.; Owaki, M.; Yamamoto, K.; Yamaguchi, R. Synthesis of five-, six-, and seven-membered ring lactams by Cp*Rh complex-catalyzed oxidative N-heterocyclization of amino alcohols. Org. Lett. 2004, 6, 2785–2788. (14) Yoo, W. J.; Li, C. J. Highly efficient oxidative amidation of aldehydes with amine hydrochloride salts. J. Am. Chem. Soc. 2006, 128, 13064–13065. (15) Ekoue-Kovi, K.; Wolf, C. Metal-free one-pot oxidative amination of aldehydes to amides. Org. Lett. 2007, 9, 3429–3432. (16) Reddy, K. R.; Maheswari, C. U.; Venkateshwar, M.; Kantam, M. L. Oxidative amidation of aldehydes and alcohols with primary amines catalyzed by KI-TBHP. Eur. J. Org. Chem. 2008, 3619–3622. (17) Gao, J.; Wang, G. W. Direct oxidative amidation of aldehydes with anilines under mechanical milling conditions. J. Org. Chem. 2008, 73, 2955–2958. (18) Chen, M.-Y.; Hsu, J.-L.; Shie, J.-J.; Fang, J.-M. Direct oxidative amidation of aldoses by iodine in ammonia water. J. Chin. Chem. Soc. 2003, 50, 129–133. (19) Colombeau, L.; Traore, T.; Compain, P.; Martin, O. R. Metal-Free One-Pot Oxidative Amidation of Aldoses with Functionalized Amines. J. Org. Chem. 2008, 73, 8647–8650. (20) Iida, S.; Togo, H. Direct and facile oxidative conversion of primary, secondary, and tertiary amines to their corresponding nitriles. Synlett 2006, 2633–2635. (21) Sanki, A. K.; Talan, R. S.; Sucheck, S. J. Synthesis of Small Glycopeptides by Decarboxylative Condensation and Insight into the Reaction Mechanism. J. Org. Chem. 2009, 74, 1886–1896. (22) Lonngren, J.; Goldstein, I. J.; Niederhuber, J. E. Aldonate coupling, a simple procedure for preparation of carbohydrate-protein conjugates for studies of carbohydrate-binding proteins. Arch. Biochem. Biophys. 1976, 175, 661–669. (23) Fujimoto, K.; Miyata, T.; Aoyama, Y. Saccharide-directed cell recognition and molecular delivery using macrocyclic saccharide clusters: Masking of hydrophobicity to enhance the saccharide specificity. J. Am. Chem. Soc. 2000, 122, 3558–3559. (24) Narain, R.; Armes, S. P. Direct synthesis and aqueous solution properties of well-defined cyclic sugar methacrylate polymers. Macromolecules 2003, 36, 4675–4678. (25) Hayashida, O.; Hamachi, I. Fluorophore appended saccharide cyclophane: Self-association, fluorescent properties, heterodimers with cyclodextrins, and cross-linking behavior with peanut agglutinin of dansyl-modified saccharide cyclophane. J. Org. Chem. 2004, 69, 3509–3516. (26) Yang, B. Y.; Montgomery, R. Oxidation of lactose with bromine. Carbohydr. Res. 2005, 340, 2698–2705. (27) Kida, T.; Tanaka, T.; Nakatsuji, Y.; Akashi, M. Formation of micrometer-sized supramolecular assemblies with unique morphologies from triple-chain lipids with two sugar head groups. Chem. Lett. 2006, 35, 112–113. (28) El, A., ESH; Awad, L. F.; Hamid, H. A.; Atta, A. I. MAOS of D-gluconic acid, D-glucono-1,4- and 1,5-lactones, esters, hydrazides, and benzimidazoles thereof. J. Carbohydr. Chem. 2007, 26, 329–338. (29) Morimoto, N.; Ogino, N.; Narita, T.; Kitamura, S.; Akiyoshi, K. Enzyme-responsive molecular assembly system with amylose-primer surfactants. J. Am. Chem. Soc. 2007, 129, 458–459. (30) Kim, K.; Matsuura, K.; Kimizuka, N. Binding of lectins to DNA micro-assemblies: Modification of nucleo-cages with lactose-conjugated psoralen. Bioorg. Med. Chem. 2007, 15, 4311–4317. (31) Borch, R. F.; Bernstei, M. D.; Durst, H. D. Cyanohydridoborate anion as a selective reducing agent. J. Am. Chem. Soc. 1971, 93, 2897–2904. (32) Gildersleeve, J. C.; Oyelaran, O.; Simpson, J. T.; Allred, B. Improved procedure for direct coupling of carbohydrates to proteins via reductive amination. Bioconjug. Chem. 2008, 19, 1485–1490. (33) Halkes, K. M.; Souza, A. C.; Maljaars, C. E. P.; Gerwig, G. J.; Kamerling, J. P. A facile method for the preparation of gold glyconanoparticles from free oligosaccharides and their applicability in carbohydrate-protein interaction studies. Eur. J. Org. Chem. 2005, 3650–3659. (34) Andersen, K. E.; Bjergegaard, C.; Sorensen, H. Analysis of reducing carbohydrates by reductive tryptamine derivatization prior to micellar electrokinetic capillary chromatography. J. Agric. Food Chem. 2003, 51, 7234–7239. (35) Nakajima, K.; Oda, Y.; Kinoshita, M.; Masuko, T.; Kakehi, K. Time-resolved fluorometric analysis of carbohydrates labeled with amino-aromatic compounds by reductive amination. Analyst 2002, 127, 972–976. (36) Huang, G. L.; Zhang, H. C.; Wang, P. G. Fabrication and application of neoglycolipid arrays in a microtiter plate. Bioorg. Med. Chem. Lett. 2006, 16, 2031–2033. (37) Dalpathado, D. S.; Jiang, H.; Kater, M. A.; Desaire, H. Reductive amination of carbohydrates using NaBH(OAc)(3). Anal. Bioanal. Chem. 2005, 381, 1130–1137. (38) Nishimura, S. I.; Niikura, K.; Kurogochi, M.; Matsushita, T.; Fumoto, M.; Hinou, H.; Kamitani, R.; Nakagawa, H.; Deguchi, K.; Miura, N.; Monde, K.; Kondo, H. High-throughput protein glycomics: Combined use of chemoselective glycoblotting and MALDI-TOF/TOF mass spectrometry. Angew. Chem., Int. Ed. 2005, 44, 91–96. (39) Lohse, A.; Martins, R.; Jorgensen, M. R.; Hindsgaul, O. Solid-phase oligosaccharide tagging (SPOT): Validation on glycolipid-derived structures. Angew. Chem., Int. Ed. 2006, 45, 4167–4172. (40) Vila-Perello, M.; Gallego, R. G.; Andreu, D. A simple approach to well-defined sugar-coated surfaces for interaction studies. Chembiochem 2005, 6, 1831–1838. (41) Zhou, X. C.; Zhou, J. H. Oligosaccharide microarrays fabricated on aminooxyacetyl functionalized glass surface for characterization of carbohydrate-protein interaction. Biosens Bioelectron 2006, 21, 1451–1458. (42) Guillaumie, F.; Thomas, O. R. T.; Jensen, K. J. Immobilization of pectin fragments on solid supports: Novel coupling by thiazolidine formation. Bioconjug. Chem. 2002, 13, 285–294. (43) Gray, G. R. Direct coupling of oligosaccharides to proteins and derivatived gels. Arch. Biochem. Biophys. 1974, 163, 426–428. (44) Lee, M.; Shin, I. Facile preparation of carbohydrate microarrays by site-specific, covalent immobilization of unmodified carbohydrates on hydrazide-coated glass slides. Org. Lett. 2005, 7, 4269–4272. (45) Zhi, Z. L.; Powell, A. K.; Turnbull, J. E. Fabrication of carbohydrate microarrays on gold surfaces: Direct attachment of nonderivatized oligosaccharides to hydrazide-modified self-assembled monolayers. Anal. Chem. 2006, 78, 4786–4793. (46) de, P., JL; Seeberger, P. H. Recent advances in carbohydrate microarrays. QSAR Comb. Sci. 2006, 25, 1027–1032. (47) Feizi, T.; Fazio, F.; Chai, W. C.; Wong, C. H. Carbohydrate microarrays - a new set of technologies at the frontiers of glycomics. Curr. Opin. Struct. Biol. 2003, 13, 637–645. (48) Monzo, A.; Guttman, A. Immobilization techniques for mono- and oligosaccharide microarrays. QSAR Comb. Sci. 2006, 25, 1033–1038. (49) Brun, M. A.; Disney, M. D.; Seeberger, P. H. Miniaturization of microwave-assisted carbohydrate functionalization to create oligosaccharide microarrays. Chembiochem 2006, 7, 421–424. (50) Huang, C. Y.; Thayer, D. A.; Chang, A. Y.; Best, M. D.; Hoffmann, J.; Head, S.; Wong, C. H. Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. PNAS 2006, 103, 15–20. (51) Manimala, J. C.; Roach, T. A.; Li, Z. T.; Gildersleeve, J. C. High-throughput carbohydrate microarray analysis of 24 lectins. Angew. Chem., Int. Ed. 2006, 45, 3607–3610. (52) Liang, P. H.; Wang, S. K.; Wong, C. H. Quantitative analysis of carbohydrate-protein interactions using glycan microarrays: Determination of surface and solution dissociation constants. J. Am. Chem. Soc. 2007, 129, 11177–11184. (53) Zou, L.; Pang, H. L.; Chan, P. H.; Huang, Z. S.; Gu, L. Q.; Wong, K. Y. Covalent immobilization of carbohydrates on sol-gel-coated microplates. Analyst 2008, 133, 1195–1200. (54) Wang, C. C.; Huang, Y. L.; Ren, C. T.; Lin, C. W.; Hung, J. T.; Yu, J. C.; Yu, A. L.; Wu, C. Y.; Wong, C. H. Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer. PNAS 2008, 105, 11661–11666. (55) Michel, O.; Ravoo, B. J. Carbohydrate Microarrays by Microcontact 'Click' Chemistry. Langmuir 2008, 24, 12116–12118. (56) Park, S.; Lee, M. R.; Shin, I. Carbohydrate microarrays as powerful tools in studies of carbohydrate-mediated biological processes. Chem. Commun. 2008, 4389–4399. (57) Chen, M. L.; Adak, A. K.; Yeh, N. C.; Yang, W. B.; Chuang, Y. J.; Wong, C. H.; Hwang, K. C.; Hwu, J. R. R.; Hsieh, S. L.; Lin, C. C. Fabrication of an Oriented Fc-Fused Lectin Microarray through Boronate Formation. Angew. Chem., Int. Ed. 2008, 47, 8627–8630. (58) Pohl, N. L. Fluorous tags catching on microarrays. Angew. Chem., Int. Ed. 2008, 47, 3868–3870. (59) Laurent, N.; Voglmeir, J.; Flitsch, S. L. Glycoarrays - tools for determining protein-carbohydrate interactions and glycoenzyme specificity. Chem. Commun. 2008, 4400–4412. (60) Bryan, M. C.; Fazio, F.; Lee, H. K.; Huang, C. Y.; Chang, A.; Best, M. D.; Calarese, D. A.; Blixt, C.; Paulson, J. C.; Burton, D.; Wilson, I. A.; Wong, C. H. Covalent display of oligosaccharide arrays in microtiter plates. J. Am. Chem. Soc. 2004, 126, 8640–8641. (61) Ko, K. S.; Jaipuri, F. A.; Pohl, N. L. Fluorous-based carbohydrate microarrays. J. Am. Chem. Soc. 2005, 127, 13162–13163. (62) Jaipuri, F. A.; Collet, B. Y. M.; Pohl, N. L. Synthesis and quantitative evaluation of Glycero-D-manno-heptose binding to concanavalin a by fluorous-tag assistance. Angew. Chem., Int. Ed. 2008, 47, 1707–1710. (63) Chen, G. S.; Pohl, N. L. Synthesis of fluorous tags for incorporation of reducing sugars into a quantitative microarray platform. Org. Lett. 2008, 10, 785–788. (64) Talukdar, S.; Hsu, J. L.; Chou, T. C.; Fang, J. M. Direct transformation of aldehydes to nitriles using iodine in ammonia water. Tetrahedron Lett. 2001, 42, 1103–1105. (65) Shie, J. J.; Fang, J. M. Direct conversion of aldehydes to amides, tetrazoles, and triazines in aqueous media by one-pot tandem reactions. J. Org. Chem. 2003, 68, 1158–1160. (66) Shie, J. J.; Fang, J. M. Microwave-assisted one-pot tandem reactions for direct conversion of primary alcohols and aldehydes to triazines and tetrazoles in aqueous media. J. Org. Chem. 2007, 72, 3141–3144. (67) Davis, B. G. Synthesis of glycoproteins. Chem. Rev. 2002, 102, 579–601. (68) Larsen, K.; Thygesen, M. B.; Guillaumie, F.; Willats, W. G. T.; Jensen, K. J. Solid-phase chemical tools for glycobiology. Carbohydr. Res. 2006, 341, 1209–1234. (69) Fazio, F.; Bryan, M. C.; Lee, H. K.; Chang, A.; Wong, C. H. Assembly of sugars on polystyrene plates: a new facile microarray fabrication technique. Tetrahedron Lett. 2004, 45, 2689–2692. (70) Harvey, D. J. Electrospray mass spectrometry and fragmentation of N-linked carbohydrates derivatized at the reducing terminus. J. Am. Soc. Mass Spectrom. 2000, 11, 900–915. (71) Fischer, K.; Wacht, M.; Meyer, A. Simultaneous and sensitive HPLC determination of mono- and disaccharides, uronic acids, and amino sugars after derivatization by reductive amination. Acta. Hydroch. Hydrob. 2003, 31, 134–144. (72) Witt, K. A.; Davis, T. P. CNS drug delivery: opioid peptides and the blood-brain barrier. AAPS J. 2006, 8, E76–88. (73) Poduslo, J. F.; Curran, G. L. Glycation increases the permeability of proteins across the blood nerve and blood-brain barriers. Mol. Brain Res. 1994, 23, 157–162. (74) Jakas, A.; Horvat, S. The effect of glycation on the chemical and enzymatic stability of the endogenous opioid peptide, leucine-enkephalin, and related fragments. Bioorg. Chem. 2004, 32, 516–526. (75) Pan, W. D.; Ansiaux, C.; Vincent, S. P. Synthesis of acyclic galactitol- and lyxitol-aminophosphonates as inhibitors of UDP-galactopyranose mutase. Tetrahedron Lett. 2007, 48, 4353–4356. (76) Mieszala, M.; Kogan, G.; Jennings, H. J. Conjugation of meningococcal lipooligosaccharides through their lipid A terminus conserves their inner epitopes and results in conjugate vaccines having improved immunological properties. Carbohydr. Res. 2003, 338, 167–175. (77) Reddy, B. V. B.; Bartoszewicz, Z.; Rebois, R. V. Modification of the sialic acid residues of choriogonadotropin affects signal transduction. Cell. Signal. 1996, 8, 35–41. (78) Grimmecke, H. D.; Brade, H. Studies on the reductive amination of 3-deoxy-D-manno-octulosonic acid (Kdo). Glycoconj. J. 1998, 15, 555–562. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43656 | - |
dc.description.abstract | 在生物化學領域當中,醣類分子扮演著很重要的角色。藉由不同連結方式所形成的寡醣體往往可以調節與控制整個細胞間訊息的傳遞。為了研究醣分子的性質與特性,許多醣耦合體被開發出來模擬醣分子在生物系統當中所扮演的角色,透過這樣的方式再進一步去研究部份生物系統的機制。 在這些已經發表的論文當中,建立醣耦合體的方法大部分都需要透過一系列的化學修飾,因此也造成往後應用上的限制。
在本篇論文當中,我們實驗室針對醣類分子開發出直接建立醣類耦合體的方法。透過碘–氨的氧化作用,醛醣可以直接轉換成醯胺類化合物。一開始的目的在於開發出新式的水相有機反應,隨著後續的發展,為了能將此反應延伸到建立醣類與具有多功能性的胺類、胺基酸乃至於蛋白質的耦合體,整個實驗系統也隨著修改。透過溶劑的篩選,酸鹼性的調整,以及實驗步驟的優先順序,醛醣可以直接與胺基酸分子以及蛋白質進行耦合反應。此外,我們也透過碘–氨反應將酮酸轉換成醯胺類化合物。 在ㄧ系列的碘–氨反應當中,醛醣以及酮酸分子可以被直接且選擇性地轉換成醯胺類化合物,而醣分子上的官能基如氫氧基則無氧化反應發生,寡醣分子的醣苷鍵也沒有斷裂。進行耦合的胺類分子這ㄧ部份,雙鍵官能基團、苯環、酯基、以及氨基酸的光學中心在碘–氨反應當中相當穩定。此外透過反應步驟的調整,一鍋兩步化的程序,可以將原本無法進行耦合的胺基酸順利建立起來,而這樣的調整也間接證實反應機制傾向於透過醣類內酯化後再進行開還反應。 另外,我們利用甘露糖進行微陣列檢測的實驗,在初步的微陣列檢測結果顯示,修飾後的甘露糖醯胺依然與甘露糖專屬的辨識蛋白質(Con A)保有些微的結合力。這ㄧ系列的結果讓我們相信透過碘–氨反應所建立起的的醣分子耦合物有機會應用到研究寡醣分子的辨識以及醣蛋白的性質。 | zh_TW |
dc.description.abstract | Carbohydrates are essential materials in many biological processes. They can maintain and modulate the intrinsic properties of proteins. Glycoconjugates have become popular tools to investigate the biological processes. Many conjugation methods have been developed by anchoring carbohydrates to proteins. However, some of these methods may be time-consuming and result in low overall yield due to many preparation steps.
Here we report a direct conjugation method by forming a robust amide bond between amine and aldehyde on the reducing end of aldose. By using iodine, an aldose was directly coupled with an amine through an amide bond in aqueous solution. Accordingly, aldoses undergo an oxidative amidation with a variety of aliphatic amines, bifunctional amines, α-amino esters, and peptides. Under this condition, the hydroxy groups on sugar skeleton are unaffected, the glycosidic bonds of the oligosaccharides are retained, and the amidation selectively occurs at the reducing end without interfering with other functional groups, e.g., the carboxy group in glucuronic acid. Various groups, such as double bond, phenyl, and ester are also inert in this condition. Furthermore, this reaction protocol was applied to conjugation of α-keto acids with amines by a sequence of decarboxylation, oxidation, and in situ amidation. It was promising to utilize this novel conjugation method for preparation of neoglycoproteins and neoglycolipids from unprotected and unmodified carbohydrates. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T02:25:20Z (GMT). No. of bitstreams: 1 ntu-98-D94223005-1.pdf: 289194167 bytes, checksum: 71e4faf5596c4c2bfaa899af50ffe78d (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | Acknowledgement............................................................................................................I
Abstract in Chinese.......................................................................................................III Abstract in English.........................................................................................................V Table of Contents.........................................................................................................VII Index of Figures...........................................................................................................XII Index of Schemes........................................................................................................XIV Index of Tables.............................................................................................................XV Abbreviations............................................................................................................XVII Chapter 1. Introduction..................................................................................................1 1.1 Amides............................................................................................................1 1.2 Direct oxidative amidation from alcohols, aldehydes, and ketoacids.......4 1.2.1 Using transition metal catalysts...........................................................4 a. Nickel peroxide....................................................................................4 b. Palladium.............................................................................................5 c. Ru..........................................................................................................7 d. Rh complex.........................................................................................10 e. Cu........................................................................................................11 1.2.2 Metal free amidation..........................................................................12 a. TBHP...................................................................................................12 b. Oxone...................................................................................................13 c. Iodine...................................................................................................14 d. Hydroxylamine and ketoacid............................................................16 1.3 Glycocojugation...........................................................................................19 1.3.1 Reductive amidation...........................................................................19 1.3.2 Oxime linkage.....................................................................................21 1.3.3 Thiazolidine formation.......................................................................23 1.3.4 Activated aldonate..............................................................................23 1.3.5 Hydrazide linkage...............................................................................24 1.3.6 Imidazole.............................................................................................25 1.4 Carbohydrate microarrays.........................................................................26 1.4.1 Site-specific and covalent immobilization........................................26 1.4.2 Site-specific but noncovalent immobilization...................................27 Chapter 2. Results and Discussion...............................................................................29 2.1 Amidation of aldoses by treatment of iodine in ammonia water............32 2.2 Amidation of aldoses with aqueous amines...............................................35 2.2.1 Isolation and characterization of gluconamide peracetate.............36 2.2.2 Isolation and characterization of N-ethyl gluconamide..................38 2.2.3 The amount of iodine used in the oxidative amidation reactions...39 2.2.4 Some general aldoses for oxidative amdation in ethylamine solution.................................................................................................40 2.2.5 Summary of oxidative amidation of aldoses in aqeous media........42 2.3 Amidation of aldoses with alkylamines.....................................................43 2.3.1 Preliminary study of solvents in iodine-promoted oxidaitve amidation.............................................................................................44 2.3.2 Steric effect of the primary, secondary and tertiary amines..........47 2.3.3 Amidation of diverse aldoses with aliphatic amines........................49 2.4 Amidation of aldose with functional amines.............................................53 2.4.1 Amidation of aldoses with amines bearing other functionalities...53 2.4.2 Amidation of aldoses with aromatic amines: limitation of our current method...................................................................................57 2.5 Iodine-promoted oxidative amidation of aldose with amine HCl salt....59 2.5.1 Effect of pH value...............................................................................59 2.5.2 Optimization of iodine-promoted amidation...................................62 2.6 Amidation of aldoses with α-amino acid...................................................63 2.6.1 Amidaiton of aldose with HCl salts of amino esters........................64 2.6.2 One-pot two-step protocol..................................................................65 2.6.3 Selective ligation of aldose with L-lysine methyl ester.....................69 2.6.4 One-pot two-step iodine-promoted oxidative amidations with cysteine.................................................................................................72 2.7 Amidation of aldoses with peptides and proteins.....................................73 2.7.1 Amidation of glucose with dipeptides...............................................73 2.7.2 Glutathione..........................................................................................74 2.7.3 Iodine-promoted oxidative amidation of glucose with GSH, and GSSG...................................................................................................78 2.7.4 Iodine-promoted oxidative amidation of D-lactose with BSA........79 2.8 Mechanistic study........................................................................................84 2.9 Decaboxylative amidation of α-keto acids.................................................86 2.9.1 Decarboxylative amidation of 2-keto-L-gulonic acid.......................87 2.9.2 Decarboxylative amidation of sialic acids........................................88 2.10 Preliminary assay of aldonamides on microarray.................................90 2.11 Conclusion..................................................................................................93 Chapter 3. Experimental Section.................................................................................95 3.1 General part.................................................................................................95 3.2 General procedure for the iodine-promoted amidation of carbohydrate molecules with primary amines.................................................................96 3.3 General procedure for oxidative amidation of aldoses with the methyl esters of α-amino acid and peptides...........................................................97 3.4 Procedure for microarray assay.................................................................97 3.5 Synthesis and characterization of compounds..........................................99 Chapter 4. References.................................................................................................170 Appendices (1H & 13C NMR Spectra, published paper)..........................................180 | |
dc.language.iso | en | |
dc.title | 研究醛醣與酮酸之醯胺化反應:直接建立醣類耦合體之方法與應用 | zh_TW |
dc.title | Direct Amidation of Aldoses and Decarboxylative Amidation of alpha-Keto Acids: An Efficient Conjugation Method for Unprotected Carbohydrate Molecules | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 陳平,邱勝賢,李文山,梁碧惠,楊文彬 | |
dc.subject.keyword | 醯胺化,碘,醛醣,酮酸, | zh_TW |
dc.subject.keyword | amidation,iodine,aldose,ketoacid, | en |
dc.relation.page | 268 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-08-18 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
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