簡易檢索 / 詳目顯示
| 研究生： |
胡育朋 Yu-Peng Hu |
|---|---|
| 論文名稱： |
玻尿酸之合成研究 Synthesis of Hyaluronic Acid |
| 指導教授： |
洪上程
Shang-Cheng Hung 楊吉水 Jye-Shane Yang |
| 口試委員: | |
| 學位類別： |
碩士 Master |
| 系所名稱： |
理學院 - 化學學系 Department of Chemistry |
| 畢業學年度： | 93 |
| 語文別： | 中文 |
| 論文頁數： | 89 |
| 中文關鍵詞： | 透明質酸 、合成 、玻尿酸 |
| 外文關鍵詞： | Synthesis, Hyaluronic Acid |
| 相關次數： | 點閱：13 下載：0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
玻尿酸是唯一一種不含有硫酸乙醯形式，並且不存在於細胞表面的葡胺巨醣分子，它是由D型乙醯葡萄胺醣 (N-acetyl-D-glucosamine)與D型葡萄醣酸(D-glucuronic acid)以β1-3和β1-4鍵結所建構而成的雙醣體為基本單元，再重複組合而成的多醣體。玻尿酸在人體內，扮演著多樣的角色，包括了細胞的聚集、細胞周圍基質的維持、細胞與基質間訊號的傳遞、細胞的移動、血管新生和腫瘤的轉移等等。
我們利用實驗室已開發的一鍋化組合保護製程，經由一步驟的處理去合成D式葡萄硫苷醣衍生物39，之後再經兩步反應，可得醣受體36 ; 另外，也以一鍋化反應獲得化合物52，再經三步驟的處理，取得醣予體50。其後以化合物36和50，去進行醣鏈結反應，可獲得高產率且高選擇性的雙醣49，此後，再經過六步的官能基轉換，可成功合成玻尿酸雙醣分子63。
Hyaluronic acid is a linear, non-sulfated, and extracellular polymer of disaccharide repeating units which are termed as [4)-β-D-glucuronic acid-(1→3)-β-D-N-acetyl glucosamine-(1→]n. The most important biological functions of hyaluronic acid include cell-cell aggregation, cell-cell communication, cell adhesion, angiogenisis, and tumor metastasis.
We tried to synthesize the p-methylphenyl-1-thio-β-D-glucose-derived 39 and D-glucosamine-derived 52 by utilizing the one-pot protection strategy which was successfully developed in our laboratory. The acceptor 36 was able to be prepared from compound 39 in two steps. On the other hand, donor 50 can be afforded by using 52 as starting material in two steps. Coupling of 36 with 50 gave the β-linked disaccharide 49 in high yield and selectivity. The target molecular 63 could be generated via the subsequent functional group transformation in 6 steps.
1. Borman, S. C&EN 1993, Jun. 28, 27.
2. Liu, J.; Thorp, S. C. Med. Res. Rev. 2002, 22, 1.
3. Valki, A. In Essentials of Glycobiology; Varki, A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.; Marth, J. Eds.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, New York, 1999, pp 1.
4. Karst, N. A.; Linhardt, R. J. Curr. Med. Chem. 2003, 10, 1993.
5. Raman, R.; Sasisekharan, V.; Sasisekharan1, R. Chem. Bio. 2005, 12, 267.
6. Hyaluronan Today ( http://www.glycoforum.gr.jp/science/hyaluronan/hyaluronanE.html)
7. Weissman B., Meyer K. J. Am. Chem. Soc. 1954, 76, 1753.
8. Scott JE, Cummings C., Brass A., Chen Y. Biochem. J. 1991, 274, 699.
9. Scott JE., Presti D., Cell Biochemistry and Function 1994, 12, 281.
10. Meyer, K.; Palmer, J. W. J. Biol. Chem. 1934, 107, 629.
11. Laurent, T. C.; Fraser, J. R. E. FASEB J. 1992, 6, 2397.
12. Weigel, P. H.; Hascall, V. C.; Tammi, M. J. Biol. Chem. 1997, 272, 13997.
13. Sugahara KN, Murai T., Nishinakamura H., Kawashima H., Saya H., Miyasaka M. J. Biol. Chem. 2003, 278, 32259.
14. Okamoto I., Kawano Y., Murakami D., Sasayama T., Araki N., Miki T., Wong AJ, Saya H. J. Cell. Biol. 2001,155, 755.
15. Roscic-Mrkic B., Fischer M., Leemann C., Manrique A., Gordon CJ, Moore JP, Proudfoot AE, Trkola A. Blood, 2003, 102, 1169.
16. Murai T., Miyazaki Y., Nishinakamura H., Sugahara KN, Miyauchi T., Sako Y., Yanagida T., Miyasaka M. J. Biol. Chem. 2004, 279, 4541.
17. Bourguignon LYW, Zhu H., Shao L., Chen Y. J. Biol. Chem. 2001, 276, 7327.
18. Embry J., Knudson W. Arthritis Rheum 2003, 48, 3431.
19. Jiang H, Knudson CB, Knudson W. Arthritis Rheum 2001, 44, 2599.
20. Yu Q., Toole BP. J. Biol. Chem. 1996, 271, 20603.
21. The Chemistry, Biology and Medical Applications of Hyaluronan and its Derivatives; Laurent, T. C. ED.; Wenner-Gren International Series, Vol. 72. London, UK: Portland Press, 1998.
22. Perschl, A.; Lesley, J.; English, N,; Trowbridge, I.; Hyman, R. Eur. J. Immunol. 1995, 25, 495.
23. Nakahara, Y.; Ogawa, T. Carbohydr. Res. 1987, 167, C1.
24. Slaghek, T.; Nakahara, Y.; Ogawa, T. Tetrahedron Lett. 1992, 33, 4971.
25. Slaghek, T.; Nakahara, Y.; Ogawa, T.; Kamerling, J.P.; Vliegenthart, F. G. Tetrahedron Lett. 1993, 34, 7939.
26. Slaghek, T.; Nakahara, Y.; Ogawa, T.; Kamerling, J.P.; Vliegenthart, J. F. G. Carbohydr. Res. 1994, 255, 61.
27. Slaghek, T.; Nakahara, Y.; Ogawa, T.; Kamerling, J.P.; Vliegenthart, J. F. G. Tetrahedron Assym. 1994, 5, 2291.
28. Halkes, K. M.; Slaghek, T.; Hypponen, T. K.; Kruiskamp, P. H.; Ogawa, T.; Kamerling, J. P. Vliegenthart, J. F. G. Carbohydr. Res. 1998, 309, 161.
29. Blatter,G. ; Jacquinet, J. C. Carbohydr. Res. 1996, 288, 109.
30. Yeung, B. K. S.; Hill, D. C.; Janicka, M.; Petillo, P. A. Org. Lett. 2000, 2, 1279.
31. Adamski-Werner, S. L.; Yeung, B. K. S.; Miller-Deist, L. A.; Petillo, P. A. Carbohydr. Res. 2004, 339, 1255.
32. Palmacci, E. R.; Seeberger, P. H. Tetrahedron 2004, 60, 7755.
33. De Luca, C.; Lansing, M.; Martini, I.; Crescenzi, F.; Shen, G.-J.; O’Regan, M.; Wong, C.-H. J. Am. Chem. Soc. 1995, 117, 5869.
34. Kobayashi, S.; Morii, H.; Itoh, R.; Kimura, S.; Ohmae, M. J. Am. Chem. Soc. 2001, 123, 11825.
35. Tawada, A.; Masa, T.; Oonuki, Y.; Watanabe, A.; Matsuzaki, Y.; Asari, A. Glycobiology 2002, 12, 421.
36. 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, 2360.
37. 國立清華大學博士論文，2003年，李靜琪，細胞表面硫酸乙醯肝素寡醣的合成研究。
38. Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996, 37, 6029.
39. Fiandor, J.; Garcia-Lopez, M. T.; Delas-Heras, F. G.; Mendez-Castrillon, P. P. Synthesis 1985, 1221.
40. Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50, 21-123.
41. Pozsgay, V. J. Am. Chem. Soc. 1995, 117, 6673.
42. Sharma, G. V. M.; Ilangovan, A. Synlett 1999, 1963.
43. Srivastava, V. K.; Sondheimer, S. J. Schuerch, C. Carbohydr. Res.1980, 86, 203.
44. Cheung, A.; Sidduri A.; Robert A. Tetrahedron Letters 2000, 41, 3303.
45. Demchenko, Alexei V.; Rousson, E.; Boons, Geert-Jan. Tetrahedron Letters 1999, 40, 6523.
46. Yeung, , B. K. S.; Adamski-Werner, S. L.; Bernard, J. B.; Poulenat, J. ; Petillo, P. A. Org. Lett. 2000, 2, 3135.
