Title page for 91223035


[Back to Results | New Search]

Student Number 91223035
Author Guan-Rong Pan(潘冠榮)
Author's Email Address s1223035@cc.ncu.edu.tw
Statistics This thesis had been viewed 1723 times. Download 996 times.
Department Chemistry
Year 2003
Semester 2
Degree Master
Type of Document Master's Thesis
Language zh-TW.Big5 Chinese
Title Synthesis of Heparan Sulfate Disaccharides
Date of Defense 2004-07-09
Page Count 101
Keyword
  • Heparan Sulfate
  • Abstract Abstract
      Heparan sulfate, a complex polysaccharide belonging to the family of glycosaminoglycan, is ubiquitously distributed on the cell surface and in the extracellular matrix. It play significant roles in a diverse set of biological processes, including viral invasion, cell growth, blood coagulation, and tumor metastasis. The disaccharides 1 and 2, having a 3-O-sulfated D-glucosamine unit, are minor but very important components in heparan sulfate and are known to play a crucial role in Herpes Simplex virus entry as well as blood coagulation. The preparation of compound 4 has been carried out in our laboratory. In this thesis, we report a formal synthesis of the disaccharide 5.
      An efficient and novel preparation of the 1,6-anhydro-?-L-idopyranose 9 from comically available diacetone ?-D-glucose in five steps was successfully developed in our laboratory. Coupling of 9 with the D-glucosamine-derived donor 34 gave the ?-linked disaccharide 35? in high yield and selectivity. Subsequent anomeric deprotection, imidation and concomitant glycosylation using methanol as an acceptor successfully furnishes the requisite ?-methyl glycoside 37?. We believe that the target molecule 5 could be generated via functional group transformation of disaccharide 37? in seven steps, according to the developed method in our laboratory.
    Table of Content 目錄
      中文摘要----------------------------------------------------------------i
      英文摘要----------------------------------------------------------------ii
      謝誌--------------------------------------------------------------------iii
      縮寫對照表---------------------------------------------------------------iv
      目錄---------------------------------------------------------------------vi
    壹、緒言-----------------------------------------------------------------1
    貳、反合成分析-----------------------------------------------------------9
    參、結果與討論-----------------------------------------------------------11
    (一)、D式葡萄胺醣衍生物22的合成------------------------------------------11
       (二)、雙醣體21?的合成----------------------------------------------13
    (三)、對化合物21?醋酸酐開環反應的探討-----------------------------------16
    (四)、D式葡萄胺醣衍生物34的合成------------------------------------------18
       (五)、雙醣體36的合成----------------------------------------------19
       (六)、目標雙醣體5的合成------------------------------------------20
    肆、結論-----------------------------------------------------------------24
    伍、實驗部分-------------------------------------------------------------25
    陸、參考文獻-------------------------------------------------------------51
    柒、光譜附錄------------------------------------------------------------56
    Reference 伍、參考文獻
    1.Borman, S. C&E News 1993, Jun, 28, 27-34.
    2.Liu, J.; Thorp, S. C. Med. Res. Rev. 2002, 22, 1-25.
    3.Valki, A. In Essentials of glycobiology; Valki, A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.; Marth, J.; Eds.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, New York, 1999, pp 1-15.
    4.Pellegrini, L.; Burke, D. F.; von Delft, F.; Mulloy, B.; Blundell, T. L. Nature 2000, 407, 1029-1034.
    5.Conrad, H. E. Heparin-Binding Proteins; Academic Press: New York, 1998.
    6.Lindahl, U. Pure. Appl. Chem. 1997, 69, 1897-1902.
    7.Lane, D. A.; Björk, I.; Lindahl, U. Heparin and related polysaccharides; Plenum Press: New York, 1992.
    8.Lookene, A.; Cherreuil, O; Ostergaard, P.; Oilvecrona, G. Biochemistry 1996, 35, 12155-12163.
    9.Shukla, D.; Liu, J.; Blaiklock, P.; Shworak, N. W.; Bai, X.; Esko, J. D.; Cohen, G. H.; Kisenberg, R. J.; Rosenberg, R. D.; Spear, P. G. Cell 1999, 99, 13-22.
    10.Lindal, U.; Bäckström, G.; Thunberg. L.; Leder, I. G. Proc. Natl. Acad. Sci. USA 1980, 77, 6551-6555.
    11.Shukla, D.; Liu, J.; Blaiklock, P.; Shworak, N. W.; Bai, X.; Esko, J. D.; Cohen, G. H.; Kisenberg, R. J.; Rosenberg, R. D.; Spear, P. G. Cell 1999, 99, 13-22.
    12.Chen, Y.; Maguire, T.; Hileman, R. E.; Fromm, J. R.; Esko, J. D.; Lindardt, R. J.; Marks, R. M. Nature Medicine 1997, 3, 866-871.
    13.Jacquinet, J.-C.; Petitou, M.; Duchaussoy, P.; Lederman, I.; Choay, J.; Torri.; Sinaÿ, P. Carbohydr. Res. 1984, 130, 221-241.
    14.van Boeckel, C. A. A.; Beetz, T.; Vos, J. N.; de Jong, A. J. M.; van den Bosch, R. H.; Mertens, J. M. R; Van der Vlugt; F. A. J. Carbohydr. Chem. 1985, 4, 293-321.
    15.(a) Ichikawa, Y.; Monden, R.; Kuzuhara, H. Carbohydr. Res. 1988, 172, 37-64. (b) Fujimaki, I.; Ichikawa, Y.; Kuzuhara, H. Carbohydr. Res. 1982, 101, 148-151. (c) Ichikawa, Y.; Manaka, A.; Kuzuhara, H. Carbohydr. Res. 1985, 138, 55-64. (d) Ichikawa, Y.; Ichikawa, R.; Kuzuhara, H. Carbohydr. Res. 1985, 141, 273-282.
    16.Wessel, H. P.; Labler, L.; Jschopp, T. B. Helv. Chim. Acta 1989, 72, 1268-1277.
    17.van Boeckel, C. A. A. Petitou, M. Angew. Chem. Int. Ed. Engl. 1993, 32, 1671-1690.
    18.Jaurand, G.; Tabeur, C.; Petitou, M. Carbohydr. Res. 1994, 255, 295-301.
    19.Suda, Y.; Bird, K.; Shiyama, T.; Koshida, S.; Marques, D.; Fukase, K.; Sobel, M.; Kusumoto, S. Tetrahedron Lett. 1996, 37, 1053-1056.
    20.Kovensky, J.; Duchaussoy, P.; Petitou, M.; Sinaÿ, P. Tetrahedron: Asymmetry 1996, 7, 3119-3128.
    21.Koshida, S.; Suda, Y.; Fukui, Y.; Ormsby, J.; Sobel, M.; Kusumoto, S. Bioorg. Med. Chem. Lett. 1999, 9, 3127-3132.
    22.Koshida, S.; Suda, Y.; Fukui, Y.; Ormsby, J.; Sobel, M.; Kusumoto, S. Tetrahedron Lett. 1999, 40, 5725-5728.
    23.Orgueira, H. A.; Bartolozzi, A.; Schell, P.; Litjens, R. E. J. N.; Palmacci, E. R.; Seeberger, P. H. Chem. Eur. J. 2003, 9, 140-169.
    24.Kovensky, J.; Duchaussoy, P.; Bono, F.; Salmivirta, M.; Sizun, P.; Herbert, J.-M.; Petitou, M.; Sinaÿ, P. Bioorg. Med. Chem. 1999, 7, 1567-1580.
    25.Lee, J.-C.; Lu, X.-A.; Kulkarni, S. S.; Wen, Y.-S.; Hung, S.-C.; J. Am. Chem. Soc. 2004, 126, 476-477.
    26.Lee, J.-C.; Chang, S.-W.; Liao C.-C.; Chi, F.-C.; Chen, C.-S.; Wen, Y.-S.; Wang, C.-C.; Kulkarni, S. S.; Puranik, R.; Liu, Y.-H.; Hung, S.-C. Chem. Eur. J. 2004, 10, 399- 415.
    27.González, A. G.; Brouard, I.; León, F.; Padrón, J. I.; Bermejo, J. Tetrahedron Lett. 2001, 42, 3187-3188.
    28.Pozsgay, V. J. Am. Chem. Soc. 1995, 117, 6673-3381. (b) Pozsgay, V. Angew. Chem. Int. Ed. 1998, 37, 138-142.
    29.Sharma, G. V. M.; Ilangovan, A. Synlett 1999, 1963-1965.
    30.Srivastava, V. K.; Sondheimer, S. J. Schuerch, C. Carbohydr. Res. 1980, 86, 203-214.
    31.Ning, J.; Kong, F. Tetrahedron Lett. 1999, 40, 1357-1360.
    32.Tabeur, C.; Mallet, J.-M.; Bono, F.; Herbert, J.-M.; Petitou, M.; Sinaÿ, P. Bioorg. Med. Chem. 1999, 7, 2003-2012.
    33.van Boeckel, C. A. A.; Beetz, T.; Vos, J. N.; de Jong, A. J. M.; van Aelst, S. F.; van den Bosch, R. H.; Mertens, J. M. R.; van der Vlugt, F. A. J. Carbohydr. Chem. 1985, 4, 293-321.
    34.Hung, S.-C.; Thopate, S. R.; Chi, F.-C.; Chang, S,-W.; Lee, J.-C.; Wang, C.-C.; Wen, Y.-S. J. Am. Chem. Soc. 2001, 123, 3153-3154.
    35.Hung, S.-C.; Puranik, R.; Chi, F.-C. Tetrahedron Lett. 2000, 41, 77-80.
    36.Lei, P-S.; Duchaussoy, P.; Sizun, P.; Mallet, J.-M.; Petitou, M.; Sinaÿ, P. Bioorg. Med. Chem. 1998, 6, 1337-1346.
    37.Cook, A. F.; Maichuk, D. T. J. Org. Chem. 1970, 35, 1940-1943.
    38.Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996, 37, 6029-6032.
    39.Siang, L.; Chan, T. H. Tetrahedron Lett. 1998, 39,355-358.
    40.Hijfte, L. V.; Little, R. D. J. Org. Chem. 1985, 50, 3940-3942.
    41.Hatakeyama, S.; Mori, H.; Kitano, K.; Yamada, H.; Nishizawa, M. Tetrahedron Lett. 1994, 35, 4367.
    42.Yang, W.-C.; Lu, X.-A.; Kulkarni, S. S.; Hung, S.-C. Tetrahedron Lett. 2003, 44, 7837-7840.
    43.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, 2360-2362.
    44.Fiandor, J.; Garcia-Lopez, M. T.; Delas Heras, F. G.; Mendez-Castrillon, P. P. Synthesis 1985, 1221-1223.
    45.Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem. 1994, 50. 21-123.
    46.Nishida, Y.; Takamori, Y.; Matsuda, K.; Ohrui, H.; Yamada, T.; Kobayashi, K. J. Carbohydr. Chem. 1999, 18, 985-997.
    47.Lee, J.-C.; Tai, C.-A.; Hung, S.-C. Tetrahedron Lett. 2002, 43, 851-855.
    48.(a) Pozsgay, V. J. Am. Chem. Soc. 1995, 117, 6673-3381. (b) Pozsgay, V. Angew. Chem. Int. Ed. 1998, 37, 138-142.
    49.Lubineau, A.; Meyer, E. Carbohydr. Res. 1992, 228, 191-203.
    50.國立清華大學,李靜琪,細胞表面硫酸乙醯肝素寡醣的合成研究,2003年。
    Advisor
  • Wen-Ren Li(李文仁)
  • Shang-Cheng Hung(洪上程)
  • Files
  • 91223035.pdf
  • approve in 2 years
    Date of Submission 2004-07-14

    [Back to Results | New Search]


    Browse | Search All Available ETDs

    If you have dissertation-related questions, please contact with the NCU library extension service section.
    Our service phone is (03)422-7151 Ext. 57407,E-mail is also welcomed.