化學上的研究顯示出，P. syringae品種LPS中，OPS的部分是呈現直鏈狀或是分支狀的結構。直鏈狀結構其主鏈骨架是由L-、D-或是L-/D-rhamnose構成；而分支狀結構是在rhamnose主鏈上，連結上不同或相同的的醣取代基所構成。
基於上述各點，本研究之方向為合成出丁香假單胞菌中主鏈的部分，即Rha(1→3) Rha(1→2)Rhap的三醣重複鍵結結構。利用imidate的予體活化方式，並加以控制醣基化反應中各項變因以及條件，達成合成丁香假單胞菌LPS中，OPS以rhamnose為主鏈的生物特性結構。合成的方式，是由具有拉電子保護基的醣14當作予體連結C-1位置具有硫保護基的予體19成為雙醣，而後將還原端醣的硫保護基去除並加以活化，再連結受體18，如此一一連結而製備出三醣23的結構。予體的部分，製備出具有Ac、Bz和Bn保護的單體，從反應活性及合成策略的考量，選擇了以推電子保護基Bn形式的予體14作為雙醣合成的架構。而受體部分，C-2和C-3經由一個打叉的保護再選擇性去除C-2或是C-3的保護，可以輕易地塑造出予體19以及18的先驅物。使得合成Rha(1→3) Rha(1→2)Rhap架構的三醣更加地便利可行。

Chemical studies reveal that the structure of OPS are linear or branched among P. syringae strains. The linear backbone is composed of L-, D-, or both L-and D-rhamnose. The branch OPS is composed of linear backbone with homogenous or hetrogenous saccharide substitution.
Above all, the pivot issue of this thesis is to synthesize the linear backbone motif of P. syringae, a trisaccharide structure of Rha(1→3) Rha(1→2)Rhap. Utilizing the anomeric center activation manner of imidate and manipulating all factors and condition during glycosylation, we accomplish the synthesis of rhamnose linear backbone, unique biological feature of OPS , in the P. syringae LPS. Our synthesis strategy is to prepare disaccharide which is composed of electron-donating group protected donor 14 and anomeric center thio protected acceptor 19. The reducing end of the disaccharide is follewed by deprotection and activation of anomeric center, and then perform glycosylation with acceptor 18 for further synthesis of trisaccharide structure 23. As for donor, having synthesized Ac, Bz and Bn protected donors, we choose electron-donating Bn type donor 14 as buiding block of disaccharide synthesis for the sake of reactivity and synthesis strategy consideration. As for acceptor, through a acetal protection on C-2 and C-3 follewed by selective deprotection of C-2 or C-3, we could easily create precursor of aceeptor 19 and 18. It makes the synthesis of
Rha(1→3) Rha(1→2)Rhap feature trisaccharide to be more facile.

摘要............................Ι
Abstract........................ΙΙ
第一章 緒論...................1
1-1-1 假單胞菌..................1
1-1-2 假單胞菌屬................1
1-1-3 丁香假單胞菌..............5
1-2-1 革蘭氏陰性細菌細胞壁......6
1-2-2 革蘭氏陰性細菌外壁層......7
1-2-3 Lipid A ..................9
1-2-4 核心.....................10
1-2-4 O-chain .................12
1-2-5 丁香假單胞菌OPS..........17
第二章 研究動機..............19
第三章 結果與討論............22
3-1 合成溯徑分析...............22
3-2 受體之製備.................23
3-3 予體之製備.................26
3-4 雙醣之製備.................29
3-5 三醣之製備...............30
3-6 討論......................33
3-6-1反應條件：溫度、TMSOTf量
以及反應的添加步驟.......33
3-6-2予體部分..................35
3-6-3 受體部分.................38
3-7 結論.......................39
第四章 實驗部分
4-1一般實驗方法................40
4-2實驗步驟及光譜資料..........41
參考文獻.......................80
附錄...........................84









圖目錄
圖一.革蘭氏染色法..................................................................................6
圖二.革蘭氏陽性與革蘭氏陰性細菌細胞壁的比較...............................7
圖三.LPS結構............................................................................................8
圖四.LPS結構............................................................................................9
圖五.LipidA結構.....................................................................................10
圖六. O-chain的延長與終止示意圖.......................................................13
圖七. Pseudomonas syringae pvs.coronafaciens IMV 9030 和atrofaciens IMV 8281 的OPS重複次單元..............................................................19
圖八. Xanthomonas campestris pv. campestris 8004的重複單元..........20
圖九.合成溯徑分析.................................................................................22
圖十.實驗條件示意.................................................................................34
圖十一.anomeric center活化..................................................................36
圖十二.保護基與oxonium形成的速度.................................................37
圖十三.予體和受體的相對活性硫保護基活化的醣基化反應............38
圖十四.化合物 1 1H NMR.....................................................................85
圖十五. 化合物 1 13C NMR..................................................................86
圖十六. 化合物 2 1H NMR...................................................................87
圖十七. 化合物 2 13C NMR..................................................................88
圖十八. 化合物 3 1H NMR...................................................................89
圖十九. 化合物 3 13C NMR..................................................................90
圖二十. 化合物 4 1H NMR...................................................................91
圖二十一. 化合物 5 1H NMR...............................................................92
圖二十二. 化合物 5 13C NMR............................................................93
圖二十三. 化合物 5b 1H NMR...........................................................94
圖二十四. 化合物 5b 13C NMR..........................................................95
圖二十五. 化合物 6 1H NMR...............................................................96
圖二十六. 化合物 6 13C NMR..............................................................97
圖二十七. 化合物 7 1H NMR...............................................................98
圖二十八. 化合物 7 13C NMR..............................................................99
圖二十九. 化合物 8 1H NMR.............................................................100
圖三十. 化合物 9 1H NMR.................................................................101
圖三十一. 化合物 10 1H NMR...........................................................102
圖三十二. 化合物 10 13C NMR...........................................................103
圖三十三. 化合物 11 1H NMR...........................................................104
圖三十四. 化合物 14 1H NMR...........................................................105
圖三十五. 化合物 16, 17 1H NMR.....................................................106
圖三十六. 化合物 16 ,17 13C NMR....................................................107
圖三十七. 化合物 18 1H NMR...........................................................108
圖三十八. 化合物 18 13C NMR..........................................................109
圖三十九. 化合物 19 1H NMR...........................................................110
圖四十. 化合物 19 13C NMR..............................................................111
圖四十一. 化合物 20 1H NMR...........................................................112
圖四十二. 化合物 20 13C NMR..........................................................113
圖四十三. 化合物 21 1H NMR...........................................................114
圖四十四. 化合物 22 1H NMR C6D6..................................................115
圖四十五. 化合物 22 1H NMR CDCl3...............................................116
圖四十六. 化合物 22 13C NMR..........................................................117
圖四十七. 化合物 23 1H NMR...........................................................118
圖四十八. 化合物 23 13C NMR..........................................................119
圖四十九. 化合物 24 1H NMR........................................................120
圖五十. 化合物 24 13C NMR...........................................................121
圖五十一. 化合物 25 1H NMR...........................................................122
圖五十二. 化合物 25 13C NMR..........................................................123






表目錄
表一.假單細胞屬細菌特徵......................................................................1
表二.假單細胞屬之亞群與種別的特徵...................................................2
表三.致病性假單胞菌...............................................................................3
表四.LPS核心...................................11
表五.O-chain多醣結構............................................................................16
表六.P.syringae serotypeO1和O2的OPS結構.....................................18
表七. 25和15與異丙醇的醣基化測試反應........................................29

1. Brock, T. D.; Madigan, M. T. Biology of Microorganisms, 5th ed.; Prentice-Hall: New Jersey, 1988; Chapter 19.
2. Brock, T. D.; Madigan, M. T. Biology of Microorganisms, 5th ed.; Prentice-Hall: New Jersey, 1988; Chapter 1.
3. Brenner, D. J.; Krieg, N. R.; Staley, J. T.; Garrity, G. M. Bergey’s Manual of Systematic Bacteriology, 2nd ed.; Springer: New York, 2005; Vol. 2, Part B, p323-379.
4. Raetz, C. R. H.; Whitfield, C. Anna. Rev. Biochem. 2002, 71, 635-700.
5. Caroff, M.; Karibian, D. Carbohydr. Res. 2003, 338, 2431-2447
6. Ridley, B. L.; Jeyaretnam, B. S.; Carlson, R. W. Glycobiology. 2000, 10, 1013-1023
7. Ovod, V. V.; Zdorovenko, E. L.; Aleksander S. Shashkov, A. S.; Kocharova, N. A.; Knirel, Y. A. Eur. J. Biochem. 2000, 267, 2372-2379.
8. Ovod, V. V.; Knirel, Y. A.; Samson, R.; Krohn, K. J. J. Bacteriol. 1999, 181, 6937–6947
9. Eric Glickmann, E.; Gardan, L.; Jacquet, S.; Hussain, S.; Elasri, M.; Annik Petit, A.; Dessaux, Y. Mol. Plant-Microbe Interact. 1998, 11, 156-162.
10. Zdorovenko, E. L.; Ovod, V. V.; Zatonsky, G.V.; Shashkov, A. S.; Kocharova, N. A.; Knirela, Y. A. Carbohydr. Res. 2001, 330, 505–510
11. Das, S.; Ramm, M.; Kochanowski, H.; Basui, S. J. Bacteriol. 1994, 176, 6550-6557
12. Senchenkova, S. N.; Huang, X.; Laux, P.; Knirel, Y. A.; Shashkov, A. S.; Rudolphb, K. Carbohydr. Res. 2002, 337, 1723–1728
13. Giraud, M.-F.; Naismith, J. H. Curr. Opin. Struct. Biol. 2000, 10, 687–696.
14. Werz, D. B.; Seeberger, P. H. Angew. Chem. Int. Ed. 2005, 44, 6315-6318.
15. Bedini, E.; Carabellese, A.; Barone, G.; Parrilli, M. J. Org. Chem. 2005, 70, 8064-8070.
16. Rye, C. S.; Withers, S. G. J. Am. Chem. Soc. 2002, 124, 9756-9767.
17. Paulsen, H.; Helpap, B. Carbohydr. Res. 1991, 216, 289-313.
18. Mogemark, M.; Gustafsson, L.; Bengtsson, C.; Elofsson, M.; Kihlberg, J. Org. Lett. 2004, 6 (26), 4885-4888.
19. Schmidt, R. R. Pure & Appl. Chem. 1989, 61 (7), 1257-1270.
20. Schmidt, R. R.; Castro-Palomino, J. C.; Retz, O. Pure & Appl. Chem. 1999, 71 (5), 729-744.
21. Rathore, H.; From, A. H. L.; Ahmed, K.; Fullerton, D. S. J. Med. Chem. 1986, 29, 1945-1952.
22. Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Fan, H.-F.; Pai, C.-L.; Yang, W.-C.; Lu, L.-D.; Hung, S.-C. Angew. Chem. Int. Ed. 2002, 41 (13), 2360-2362.
23. Larson, D. P.; Heathcock, C. H. J. Org. Chem. 1997, 62, 8406-8418.
24. Hummel, G.; Schmidt, R. R. Tetrahedron Lett. 1997, 38 (7), 1173-1176.
25. Wegmann, B.; Schmidt, R. R. Carbohydr. Res. 1988, 184, 254-261.
26. Yu, C.-S.; Niikura, K.; Lin, C.-C.; Wong, C.-H. Angew. Chem. Int. Ed. 2001, 40 (15), 2900-2903.
27. Bedini, E.; De Castro, C.; Erbs, G.; Mangoni, L.; Maxwell Dow, J.; Newman, M.-A.; Parrilli, M.; Unverzagt, C. J. Am. Chem. Soc. 2005, 127, 2414-2416.
28. Lohman, G. J. S.; Hunt, D. K.; Högermeier, J. A.; Seeberger, P. H. J. Org. Chem. 2003, 68, 7559-7561.
29. Chiara, J. L.; Encinas, L.; Díaz, B. Tetrahedron Lett. 2005, 46, 2445-2448.
30. Koeller, K. M.; Wong, C.-H. Chem. Rev. 2000, 100, 4465-4493.
31. Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734-753.
32. Ye, X.-S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410-2431.
33. Yu, B.; Yang, Z.; Cao, H. Current Organic Chemistry. 2005, 9, 179-194.
34. Ritter, T. K.; Mong, K.-K. T.; Liu, H.; Nakatani, T.; Wong, C.-H. Angew. Chem. Int. Ed. 2003, 42, 4657-4660.
35. Wong, C.-H.; Ye, X.-S.; Zhang, Z. J. Am. Chem. Soc. 1998, 120, 7137-7138.
36. Wang,P.; Kim,Y.-J.; Navarro-Villalobos, M.; Rohde, B. D.; Gin, D. Y. J. Am. Chem. Soc. 2005, 127, 3256-3257.
37. Plé, K. Carbohydr. Res. 2003, 338, 1441-1454.