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研究生:陳國庭
研究生(外文):Kuo-Ting Chen
論文名稱:針對細菌肽聚醣相關分子之設計、合成及生物功能探討
論文名稱(外文):Design, Synthesis and Functional Study of Bacterial Peptidoglycan Related Molecules
指導教授:梁碧惠
口試委員:陳基旺林琬琬邱浩傑王宗興
口試日期:2015-07-23
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:210
中文關鍵詞:細菌細胞壁肽聚醣轉醣酶移位酶翻轉酶胞壁醯二肽抗生素自體免疫
外文關鍵詞:bacterial cell wallpeptidoglycantransglycosylase (TGase)translocase I (MraY)flippase (MurJ)muramyl dipeptide (MDP)antibioticsinnate immune
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肽聚醣為細菌細胞壁的主要組成成分。在細菌的生長過程中,參與肽聚醣生合成的各種酵素,例如,轉醣酶 (transglycosylase,TGase)、移位酶 (translocase I,MraY)及翻轉酶 (flippase,MurJ),均對細菌的生長與存活十分的重要。因此,針對這些酵素發展抗生素,在新藥探索的領域極具潛力。肽聚醣及其前驅物,像是Park’s nucleotide、Lipid I與Lipid II,其化學結構複雜且在細菌生長過程中有相當重要的功能,長年以來,科學家對此一直深感興趣。除此之外,肽聚醣之分子片段,也在宿主抵抗細菌感染的過程中,扮演很重要的角色。然而,為了研究這些與肽聚醣相關的議題,肽聚醣分子及其前驅物之取得為必要克服之關鍵。本論文之目標為建構肽聚醣前驅物及衍生物的合成方法,用以研究分子結構對酵素作用的影響,以及開發酵素抑制劑等有待解決的問題。
我們建立利用生物催化劑(biocatalyst)輔助的合成方法,能快速且有效率的製備一系列的肽聚醣前驅物,像是Park’s nucleotide、Lipid I 與Lipid II,以及其衍生物。取得這些天然或是人為修飾的受質分子,拓展了我們研究這些分子與肽聚醣生合成酵素作用的可能性,並能更進一步的幫助我們發展對抗細菌細胞壁生合成的新型抗生素。藉由研究移位酶MraY對我們合成的Park’s nucleotide衍生物之受質特異性,我們建構出可能的Park’s nucleotide與MraY的結合結構模型,並發現一些改質後的受質分子,具有抑制MraY活性的效果。我們亦利用Lipid II為骨架並以組合式化學的策略建立分子庫,經由篩選,我們找出能使抑制轉醣酶TGase的小分子,且此分子能抑制抗藥性菌株MRSA的生長。此研究結果對發展以轉醣酶TGase為目標的抗生素,提供了一個新的發展方向。由於目前對細菌翻轉酶MurJ研究相當缺乏,我們將合成的Lipid II 分子應用於研究MurJ的相關性質,期能建構一分析平台,針對分子的受質特異性進行研究。這些研究結果將可幫助設計以移位酶MraY、轉醣酶TGase或翻轉酶MurJ為標的之抗菌藥物。
除此之外,我們亦延續之前所開發的化學方法,製備一系列的胞壁醯二肽衍生物,並研究其分子結構對NOD2刺激效果的影響。此研究結果可被應用於未來以胞壁醯二肽為基礎的免疫佐劑之發展。


The central idea of my dissertation is to use the power of organic synthesis to investigate interesting issues in biology and medicine. Peptidoglycan (PGN) and its related molecules, such as Park’s nucleotide, Lipid I and Lipid II, have long attracted the attention of synthetic organic chemists because of their complex molecular architectures and significant impacts in biology and medicine. Moreover, the peptidoglycan fragments also play an important role during the bacterial infection. Obviously, the major challenge in this field is the development of efficient and flexible synthetic routes to such complex molecules. My goal aims at the chemical synthesis of those biosynthetic intermediates to better understand the precise molecular structures, mechanisms of action, and the functional interactions involved in peptidoglycan biosynthesis. In this dissertation, two major areas of interest are described: (1) developing the methods for the synthesis and the molecular diversifying of PGN precursors (Park’s nucleotide, Lipid I, and Lipid II) for use in the studies of PGN biosynthetic enzymes; (2) preparation of structural diverse muramyl dipeptides (MDP) for innate immune study.
PGN is a key component of bacterial cell wall, which is essential for bacterial growth. The enzymes, such as transglycosylase (TGase), translocase I (MraY) and flippase (MurJ), involving in the PGN biosynthetic pathway are important and thought as potential targets of antibiotic development. However, as the prerequisite of study those biological interesting problems, those PGN related molecules are needed. We described the biocatalytic synthetic methods to provide a rapid and efficient way to generate diverse Lipid I and Lipid II molecules. At the same time, the synthesis of an upstream PGN precursor, Park’s nucleotide, was also carried out. Through the establishment of those methods, we are able to acquire the structural complex molecules for further biological studies.
Those diverse substrate-based molecules allow us to investigate the interaction between substrates and enzymes for paving the way for novel antibiotic discovery. Several achieves for our works are shown as follows: (1) Guided by the information of MraY substrate specificity, we found the modifications on uracil of Park’s nucleotide lead to the inhibitory activity against MraY. (2) The synthetic approach of Lipid II provide the opportunity to efficient generate synthetic libraries for anti-TGase study. The results shed light on that Lipid II-like molecules with GlcNAc replaced by a cinnamic acid moiety are able to inhibit TGase. (3) The diverse Lipid I and Lipid II analogues are applied in the mechanisms and substrate specificity study of MurJ flippase. This part is currently underway in our laboratory. It is anticipated that the use of these molecules as templates for the design and synthesis of new molecules may deliver useful antibacterial drugs against resistant bacteria. As another part of our interest in PGN and innate immune study, we adopted the chemistry and chemical materials to generate a series of MDP-based molecular library for studying the NOD2-mediated NF-κB production. The results showed that NOD2 receptor may recognize a broad range of substituents at the C2 position, and the presence of a methoxyl group at the C1 position of N-glycolyl MDP has a facilitating effect on potency.
Our chemistry for the preparation of those PGN related molecules allowed us to extensively explore the unsolved issues about bacterial cell wall.


誌謝…………………………………………………………………………………..i
中文摘要……………………………………………………………………………..ii
英文摘要…………………………………………………………………………….iv
List of Figures …...………….……………………………………………………viii
List of Tables …...………………………………………………………………….xi
Chapter 1. Rapid preparation of mycobacterial N-glycolyl Lipid I and N-glycolyl
Lipid II derivatives via a biocatalytic approach……………...…………….……...1
1.1. Introduction………………………………………………………………...1
1.2. Results and discussions……………………………………………………...5
1.3. Summary and perspective…………………………………………….……..12
1.4. Experimental section………………………………………………………13
Chapter 2. Structural investigation of Park’s Nucleotide on bacterial translocase
MraY……………………………………………………………………………31
2.1. Introduction……………………………………………...………………….31
2.2. Results and discussions……………………………………………………...34
2.3. Summary and perspective…………………………………………….……..49
2.4. Experimental section……………………………………………………..…50
Chapter 3. Development of Modified PGN Precursors as TGase Inhibitors….…..61
3.1. Introduction……………………………………...………………………….61
3.2. Results and discussions……………………………………………………...64
3.3. Summary and perspective…………………………………………….…..…73
3.4. Experimental section……………………………………………………..…74
Chapter 4. Structural investigation of Lipid II on bacterial flippase MurJ………..81
vii
4.1. Introduction……………………………...……………………………….....81
4.2. Results and discussions………………………………………………..…….85
4.3. Summary and perspective…………………………………………………89
4.4. Experimental section…………………………….……………………….....90
Chapter 5. Synthesis of diverse N-substituted muramyl dipeptide derivatives and
their use in a study of human NOD2 stimulation activity………………..........….95
5.1. Introduction……………………………………………...……………..…...95
5.2. Results and discussions………………………………………………..…….98
5.3. Summary and perspective……………………………………………...…..107
5.4. Experimental section………………………………………………………108
Chapter 6. Conclusions…………………….………………………..….………125
References………………………………………………………………………..127
Appendix………………………………………………………………………..….134

(1)Umesiri, F. E.; Sanki, A. K.; Boucau, J.; Ronning, D. R.; Sucheck, S. J. Med Res Rev 2010, 30, 290.
(2)Cole, S. T.; Brosch, R.; Parkhill, J.; Garnier, T.; Churcher, C.; Harris, D.; Gordon, S. V.; Eiglmeier, K.; Gas, S.; Barry, C. E.; Tekaia, F.; Badcock, K.; Basham, D.; Brown, D.; Chillingworth, T.; Connor, R.; Davies, R.; Devlin, K.; Feltwell, T.; Gentles, S.; Hamlin, N.; Holroyd, S.; Hornsby, T.; Jagels, K.; Krogh, A.; McLean, J.; Moule, S.; Murphy, L.; Oliver, K.; Osborne, J.; Quail, M. A.; Rajandream, M. A.; Rogers, J.; Rutter, S.; Seeger, K.; Skelton, J.; Squares, R.; Squares, S.; Sulston, J. E.; Taylor, K.; Whitehead, S.; Barrell, B. G. Nature 1998, 393, 537.
(3)Mdluli, K.; Spigelman, M. Current opinion in pharmacology 2006, 6, 459.
(4)Patru, M.-M.; Pavelka, M. S., Jr. J. Bacteriol. 2010, 192, 3043.
(5)Lee, M.; Hesek, D.; Suvorov, M.; Lee, W.; Vakulenko, S.; Mobashery, S. J. Am. Chem. Soc. 2003, 125, 16322.
(6)Janin, Y. L. Bioorg Med Chem 2007, 15, 2479.
(7)Barry, C. E.; Crick, D. C.; McNeil, M. R. Infectious Disorders - Drug Targets 2007, 7, 182.
(8)Mahapatra, S.; Scherman, H.; Brennan, P. J.; Crick, D. C. J. Bacteriol. 2005, 187, 2341.
(9)Raymond, J. B.; Mahapatra, S.; Crick, D. C.; Pavelka, M. S. Journal of Biological Chemistry 2005, 280, 326.
(10)Mahapatra, S.; Yagi, T.; Belisle, J. T.; Espinosa, B. J.; Hill, P. J.; McNeil, M. R.; Brennan, P. J.; Crick, D. C. J. Bacteriol. 2005, 187, 2747.
(11)Li, K.; Kurosu, M. Heterocycles 2008, 76, 455.
(12)Meng, F. C.; Chen, K. T.; Huang, L. Y.; Shih, H. W.; Chang, H. H.; Nien, F. Y.; Liang, P. H.; Cheng, T. J.; Wong, C. H.; Cheng, W. C. Org. Lett. 2011, 13, 5306.
(13)Breukink, E.; van Heusden, H. E.; Vollmerhaus, P. J.; Swiezewska, E.; Brunner, L.; Walker, S.; Heck, A. J.; de Kruijff, B. J. Biol. Chem. 2003, 278, 19898.
(14)Krstenansky, J. L.; Khmelnitsky, Y. Bioorg Med Chem 1999, 7, 2157.
(15)Yang, J.; Liu, R.; Jiang, H.; Yang, Y.; Qiao, C. Appl Microbiol Biotechnol 2011.
(16)Berglund, P. Biomol Eng 2001, 18, 13.
(17)Kurosu, M.; Mahapatra, S.; Narayanasamy, P.; Crick, D. C. Tetrahedron Lett 2007, 48, 799.
(18)Noureddini, H.; Gao, X.; Philkana, R. S. Bioresour Technol 2005, 96, 769.
(19)Schouten, J. A.; Bagga, S.; Lloyd, A. J.; de Pascale, G.; Dowson, C. G.; Roper, D. I.; Bugg, T. D. Mol Biosyst 2006, 2, 484.
(20)Cheng, T. J.; Wu, Y. T.; Yang, S. T.; Lo, K. H.; Chen, S. K.; Chen, Y. H.; Huang, W. I.; Yuan, C. H.; Guo, C. W.; Huang, L. Y.; Chen, K. T.; Shih, H. W.; Cheng, Y. S.; Cheng, W. C.; Wong, C. H. Bioorg Med Chem 2010, 18, 8512.
(21)Shih, H. W.; Chang, Y. F.; Li, W. J.; Meng, F. C.; Huang, C. Y.; Ma, C.; Cheng, T. J.; Wong, C. H.; Cheng, W. C. Angew Chem Int Ed Engl 2012.
(22)Liu, C.-Y.; Guo, C.-W.; Chang, Y.-F.; Wang, J.-T.; Shih, H.-W.; Hsu, Y.-F.; Chen, C.-W.; Chen, S.-K.; Wang, Y.-C.; Cheng, T.-J. R.; Ma, C.; Wong, C.-H.; Fang, J.-M.; Cheng, W.-C. Org. Lett. 2010, 12, 1608.
(23)van Heijenoort, J. Cellular and molecular life sciences : CMLS 1998, 54, 300.
(24)Price, N. P.; Momany, F. A. Glycobiology 2005, 15, 29R.
(25)Anderson, M. S.; Eveland, S. S.; Price, N. P. FEMS microbiology letters 2000, 191, 169.
(26)Lehrer, J.; Vigeant, K. A.; Tatar, L. D.; Valvano, M. A. J. Bacteriol. 2007, 189, 2618.
(27)Bouhss, A.; Mengin-Lecreulx, D.; Le Beller, D.; Van Heijenoort, J. Molecular microbiology 1999, 34, 576.
(28)Chung, B. C.; Zhao, J.; Gillespie, R. A.; Kwon, D. Y.; Guan, Z.; Hong, J.; Zhou, P.; Lee, S. Y. Science 2013, 341, 1012.
(29)Bugg, T. D.; Lloyd, A. J.; Roper, D. I. Infectious disorders drug targets 2006, 6, 85.
(30)Boyle, D. S.; Donachie, W. D. J. Bacteriol. 1998, 180, 6429.
(31)Price, N. P.; Tsvetanova, B. J. antibi. 2007, 60, 485.
(32)Dini, C. Current topics in medicinal chemistry 2005, 5, 1221.
(33)Hammes, W. P.; Neuhaus, F. C. J. Biol. Chem. 1974, 249, 3140.
(34)Chen, K. T.; Kuan, Y. C.; Fu, W. C.; Liang, P. H.; Cheng, T. J.; Wong, C. H.; Cheng, W. C. Chem. Eur. J. 2013, 19, 834.
(35)Liu, C. Y.; Guo, C. W.; Chang, Y. F.; Wang, J. T.; Shih, H. W.; Hsu, Y. F.; Chen, C. W.; Chen, S. K.; Wang, Y. C.; Cheng, T. J. R.; Ma, C.; Wong, C. H.; Fang, J. M.; Cheng, W. C. Org. Lett. 2010, 12, 1608.
(36)Tedaldi, L. M.; Pierce, M.; Wagner, G. K. Carbohydr. Res. 2012, 364, 22.
(37)Pesnot, T.; Jorgensen, R.; Palcic, M. M.; Wagner, G. K. Nature chemical biology 2010, 6, 321.
(38)Brandish, P. E.; Burnham, M. K.; Lonsdale, J. T.; Southgate, R.; Inukai, M.; Bugg, T. D. J. Biol. Chem. 1996, 271, 7609.
(39)Huang, L. Y.; Huang, S. H.; Chang, Y. C.; Cheng, W. C.; Cheng, T. J.; Wong, C. H. Angewandte Chemie 2014, 53, 8060.
(40)Sakoulas, G.; Moellering, R. C., Jr. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008, 46 Suppl 5, S360.
(41)Schito, G. C. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2006, 12 Suppl 1, 3.
(42)Wilke, M. S.; Lovering, A. L.; Strynadka, N. C. Current opinion in microbiology 2005, 8, 525.
(43)Levy, S. B.; Marshall, B. Nature medicine 2004, 10, S122.
(44)Hiramatsu, K. The Lancet. Infectious diseases 2001, 1, 147.
(45)Silver, L. L. Current opinion in microbiology 2003, 6, 431.
(46)Goldman, R. C.; Gange, D. Current medicinal chemistry 2000, 7, 801.
(47)Zawadzke, L. E.; Wu, P.; Cook, L.; Fan, L.; Casperson, M.; Kishnani, M.; Calambur, D.; Hofstead, S. J.; Padmanabha, R. Analytical biochemistry 2003, 314, 243.
(48)Ostash, B.; Walker, S. Current opinion in chemical biology 2005, 9, 459.
(49)Ostash, B.; Walker, S. Natural product reports 2010, 27, 1594.
(50)Cheng, T. J.; Sung, M. T.; Liao, H. Y.; Chang, Y. F.; Chen, C. W.; Huang, C. Y.; Chou, L. Y.; Wu, Y. D.; Chen, Y. H.; Cheng, Y. S.; Wong, C. H.; Ma, C.; Cheng, W. C. PNAS 2008, 105, 431.
(51)Shih, H. W.; Chen, K. T.; Chen, S. K.; Huang, C. Y.; Cheng, T. J.; Ma, C.; Wong, C. H.; Cheng, W. C. Org. Biomol. Chem. 2010, 8, 2586.
(52)Dumbre, S.; Derouaux, A.; Lescrinier, E.; Piette, A.; Joris, B.; Terrak, M.; Herdewijn, P. J. Am. Chem. Soc. 2012, 134, 9343.
(53)van Heijenoort, J. Glycobiology 2001, 11, 25R.
(54)Gloster, T. M.; Vocadlo, D. J. Nature chemical biology 2012, 8, 683.
(55)Dong, H.; Pei, Z.; Angelin, M.; Bystrom, S.; Ramstrom, O. J. Org. Chem. 2007, 72, 3694.
(56)Huang, S. H.; Wu, W. S.; Huang, L. Y.; Huang, W. F.; Fu, W. C.; Chen, P. T.; Fang, J. M.; Cheng, W. C.; Cheng, T. J.; Wong, C. H. J. Am. Chem. Soc. 2013, 135, 17078.
(57)Ciepichal, E.; Jemiola-Rzeminska, M.; Hertel, J.; Swiezewska, E.; Strzalka, K. Chemistry and physics of lipids 2011, 164, 300.
(58)Mohammadi, T.; Sijbrandi, R.; Lutters, M.; Verheul, J.; Martin, N. I.; den Blaauwen, T.; de Kruijff, B.; Breukink, E. J. Biol. Chem. 2014, 289, 14707.
(59)Butler, E. K.; Davis, R. M.; Bari, V.; Nicholson, P. A.; Ruiz, N. J. Bacteriol. 2013, 195, 4639.
(60)Mohammadi, T.; van Dam, V.; Sijbrandi, R.; Vernet, T.; Zapun, A.; Bouhss, A.; Diepeveen-de Bruin, M.; Nguyen-Disteche, M.; de Kruijff, B.; Breukink, E. The EMBO journal 2011, 30, 1425.
(61)Ruiz, N. Antimicrobial agents and chemotherapy 2009, 53, 3604.
(62)Ruiz, N. PNAS 2008, 105, 15553.
(63)Rajagopalan, M.; Maloney, E.; Dziadek, J.; Poplawska, M.; Lofton, H.; Chauhan, A.; Madiraju, M. V. FEMS microbiology letters 2005, 250, 9.
(64)Sham, L. T.; Butler, E. K.; Lebar, M. D.; Kahne, D.; Bernhardt, T. G.; Ruiz, N. Science 2014, 345, 220.
(65)Hvorup, R. N.; Winnen, B.; Chang, A. B.; Jiang, Y.; Zhou, X. F.; Saier, M. H., Jr. European journal of biochemistry / FEBS 2003, 270, 799.
(66)Adam, A.; Petit, J. F.; Wietzerbin-Falszpan, J.; Sinay, P.; Thomas, D. W.; Lederer, E. FEBS letters 1969, 4, 87.
(67)Raymond, J. B.; Mahapatra, S.; Crick, D. C.; Pavelka, M. S., Jr. J. Biol. Chem. 2005, 280, 326.
(68)Sorbara, M. T.; Philpott, D. J. Immunological reviews 2011, 243, 40.
(69)McDonald, C.; Inohara, N.; Nunez, G. J. Biol. Chem. 2005, 280, 20177.
(70)Girardin, S. E.; Philpott, D. J. European journal of immunology 2004, 34, 1777.
(71)Girardin, S. E.; Boneca, I. G.; Carneiro, L. A.; Antignac, A.; Jehanno, M.; Viala, J.; Tedin, K.; Taha, M. K.; Labigne, A.; Zahringer, U.; Coyle, A. J.; DiStefano, P. S.; Bertin, J.; Sansonetti, P. J.; Philpott, D. J. Science 2003, 300, 1584.
(72)Strober, W.; Murray, P. J.; Kitani, A.; Watanabe, T. Nature reviews. Immunology 2006, 6, 9.
(73)Geddes, K.; Magalhaes, J. G.; Girardin, S. E. Nature reviews. Drug discovery 2009, 8, 465.
(74)Chamaillard, M.; Hashimoto, M.; Horie, Y.; Masumoto, J.; Qiu, S.; Saab, L.; Ogura, Y.; Kawasaki, A.; Fukase, K.; Kusumoto, S.; Valvano, M. A.; Foster, S. J.; Mak, T. W.; Nunez, G.; Inohara, N. Nature immunology 2003, 4, 702.
(75)Inohara, N.; Ogura, Y.; Fontalba, A.; Gutierrez, O.; Pons, F.; Crespo, J.; Fukase, K.; Inamura, S.; Kusumoto, S.; Hashimoto, M.; Foster, S. J.; Moran, A. P.; Fernandez-Luna, J. L.; Nunez, G. J. Biol. Chem. 2003, 278, 5509.
(76)Grimes, C. L.; Ariyananda Lde, Z.; Melnyk, J. E.; O''Shea, E. K. J. Am. Chem. Soc. 2012, 134, 13535.
(77)Grimes, C. L.; Podolsky, D. K.; O''Shea, E. K. Bioorg. Med. Chem. Lett. 2010, 20, 6061.
(78)Girardin, S. E.; Boneca, I. G.; Viala, J.; Chamaillard, M.; Labigne, A.; Thomas, G.; Philpott, D. J.; Sansonetti, P. J. J. Biol. Chem. 2003, 278, 8869.
(79)Vollmer, W. FEMS microbiology reviews 2008, 32, 287.
(80)Coulombe, F.; Divangahi, M.; Veyrier, F.; de Leseleuc, L.; Gleason, J. L.; Yang, Y.; Kelliher, M. A.; Pandey, A. K.; Sassetti, C. M.; Reed, M. B.; Behr, M. A. The Journal of experimental medicine 2009, 206, 1709.
(81)Rubino, S. J.; Magalhaes, J. G.; Philpott, D.; Bahr, G. M.; Blanot, D.; Girardin, S. E. Innate immunity 2013, 19, 493.
(82)Ogawa, C.; Liu, Y. J.; Kobayashi, K. S. Current bioactive compounds 2011, 7, 180.
(83)Liu, C. Y.; Guo, C. W.; Chang, Y. F.; Wang, J. T.; Shih, H. W.; Hsu, Y. F.; Chen, C. W.; Chen, S. K.; Wang, Y. C.; Cheng, T. J.; Ma, C.; Wong, C. H.; Fang, J. M.; Cheng, W. C. Org. Lett. 2010, 12, 1608.
(84)Shih, H. W.; Chen, K. T.; Cheng, T. J.; Wong, C. H.; Cheng, W. C. Org. Lett. 2011, 13, 4600.
(85)Chen, P. T.; Lin, C. K.; Tsai, C. J.; Huang, D. Y.; Nien, F. Y.; Lin, W. W.; Cheng, W. C. Chemistry, an Asian journal 2015, 10, 474.
(86)Xing, S.; Gleason, J. L. Org. Biomol. Chem. 2015, 13, 1515.
(87)Hasegawa, A.; Kaneda, Y.; Goh, Y.; Nishibori, K.; Kiso, M.; Azuma, I. Carbohydr. Res. 1981, 94, 143.
(88)Roychowdhury, A.; Wolfert, M. A.; Boons, G. J. Chembiochem : a European journal of chemical biology 2005, 6, 2088.
(89)Gisch, N.; Buske, B.; Heine, H.; Lindner, B.; Zahringer, U. Bioorg. Med. Chem. Lett. 2011, 21, 3362.
(90)Hasegawa, A.; Hioki, Y.; Kiso, M.; Okumura, H.; Azuma, I. Carbohydr. Res. 1983, 123, 183.
(91)Chen, B. C.; Wu, W. T.; Ho, F. M.; Lin, W. W. J. Biol. Chem. 2002, 277, 24169.
(92)McGeary, R. P.; Wright, K.; Toth, I. J. Org. Chem.2001, 66, 5102.


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