請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59153完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 方俊民(Jim-Min Fang) | |
| dc.contributor.author | Szu-Han Chen | en |
| dc.contributor.author | 陳思涵 | zh_TW |
| dc.date.accessioned | 2021-06-16T09:16:51Z | - |
| dc.date.available | 2022-07-27 | |
| dc.date.copyright | 2017-07-27 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-07-13 | |
| dc.identifier.citation | 1. Simonsen, L.; Clarke, M. J.; Schonberger, L. B.; Arden, N. H.; Cox, N. J.; Fukuda, K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J. Infect. Dis. 1998, 178, 53–60.
2. Taubenberger, J. K.; Morens, D. M. 1918 influenza: the mother of all pandemics. Emerging Infect. Dis. 2006, 12, 15–22. 3. Suzuki, Y. Sialobiology of influenza molecular mechanism of host range variation of influenza viruses. Biol. Pharm. Bull. 2005, 28, 399–408. 4. Horimoto, T.; Kawaoka, Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat. Rev. Microbiol. 2005, 3, 591–600. 5. Subbarao, K.; Joseph, T. Scientific barriers to developing vaccines against avian influenza viruses. Nat. Rev. Immunol. 2007, 7, 267–278. 6. Wu, Y.; Wu, Y.; Tefsen, B.; Shi, Y.; Gao, G. F. Bat-derived influenza-like viruses H17N10 and H18N11. Trends Microbiol. 2014, 22, 183–191. 7. Tong, S.; Zhu, X.; Li, Y.; Shi, M.; Zhang, J.; Bourgeois, M.; Yang, H.; Chen, X.; Recuenco, S.; Gomez, J.; Chen, L.-M.; Johnson, A.; Tao, Y.; Dreyfus, C.; Yu, W.; McBride, R.; Carney, P. J.; Gilbert, A. T.; Chang, J.; Guo, Z.; Davis, C. T.; Paulson, J. C.; Stevens, J.; Rupprecht, C. E.; Holmes, E. C.; Wilson, I. A.; Donis, R. O. New world bats harbor diverse influenza A viruses. PLoS Pathog. 2013, 9, e1003657. 8. Das, K.; Aramini, J. M.; Ma, L.-C.; Krug, R. M.; Arnold, E. Structures of influenza A proteins and insights into antiviral drug targets. Nat. Struct. Mol. Biol. 2010, 17, 530–538. 9. Wilson, I. A.; Skehel, J. J.; Wiley, D. C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. Nature 1981, 289, 366–373. 10. Wilson, I. A.; Cox, N. J. Structural basis of immune recognition of influenza virus hemagglutinin. Annu. Rev. Immunol. 1990, 8, 737–771. 11. Weis, W.; Brown, J. H.; Cusack, S.; Paulson, J. C.; Skehel, J. J.; Wiley, D. C. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 1988, 333, 426–431. 12. Gambaryan, A. S.; Robertson, J. S.; Matrosovich, M. N. Effects of egg-adaptation on the receptor-binding properties of human influenza A and B viruses. Virology 1999, 258, 232–239. 13. Varghese, J. N.; Laver, W. G.; Colman, P. M. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 1983, 303, 35–40. 14. De Clercq, E. Antiviral agents active against influenza A viruses. Nat. Rev. Drug Discov. 2006, 5, 1015–1025. 15. Nishimura, K.; Kim, S.; Zhang, L.; Cross, T. A. The closed state of a H+ channel helical bundle combining precise orientational and distance restraints from solid state NMR. Biochemistry 2002, 41, 13170–13177. 16. Stouffer, A. L.; Acharya, R.; Salom, D.; Levine, A. S.; Costanzo, L. D.; Soto, C. S.; Tereshko, V.; Nanda, V.; Stayrook, S.; DeGrado, W. F. Structural basis for the function and inhibition of an influenza virus proton channel. Nature 2008, 451, 596–599. 17. Schnell, J. R.; Chou, J. J. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 2008, 451, 591–595. 18. von Itzstein, M. The war against influenza: discovery and development of sialidase inhibitors. Nat. Rev. Drug Discov. 2007, 6, 967–974. 19. Davies, W. L.; Grunert, R. R.; Haff, R. F.; Mcgahen, J. W.; Neumayer, E. M.; Paulshock, M.; Watts, J. C.; Wood, T. R.; Hermann, E. C.; Hoffman, C. E. Antiviral activity of 1-adamantanamine (amantadine). Science 1964, 144, 862–863. 20. Stephenson, I.; Nicholson, K.G. Influenza: vaccination and treatment. Eur. Respir. J. 2001, 17, 1282–1293. 21. Bright, R. A.; Medina, M. J.; Xu, X.; Perez-Oronoz, G.; Wallis, T. R.; Davis, X. M.; Povinelli, L.; Cox, N. J.; Klimov, A. I. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005, 366, 1175–1181. 22. Bright, R. A.; Shay, D. K.; Shu, B.; Cox, N. J.; Klimov, A. I. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 2006, 295, 891–894. 23. Pielak, R. M.; Schnell, J. R.; Chou, J. J. Mechanism of drug inhibition and drug resistance of influenza A M2 channel. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 7379–7384. 24. Jing, X. H.; Ma, C. L.; Ohigashi, Y.; Oliveira, F. A.; Jardetzky, T. S.; Pinto, L. H.; Lamb, R. A. Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 10967–10972. 25. Ohigashi, Y.; Ma, C. L.; Jing, X. H.; Balannick, V.; Pinto, L. H.; Lamb, R. A. An amantadine-sensitive chimeric BM2 ion channel of influenza B virus has implications for the mechanism of drug inhibition. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 18775–18779. 26. Cady, S. D.; Schmidt-Rohr, K.; Wang, J.; Soto, C. S.; DeGrado, W. F.; Hong, M. Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. Nature 2010, 463, 689–692. 27. Miller, C. A.; Wang, P.; Flashner, M. Mechaism of Arthrobacter sialophilus neuraminidase: the binding of substrates and transition-state analogs. Biochem. Biophys. Res. Commun. 1978, 83, 1479–1487. 28. Chong, A. K. J.; Pegg, M. S.; Taylor, N. R.; von Itzstein, M. Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus. Eur. J. Biochem. 1992, 207, 335–343. 29. Meindl, P.; Bodo, G.; Palese, P.; Schulman, J.; Tuppy, H. Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 1974, 58, 457–463. 30. Colman, P. M.; Varghese, J. N.; Laver, W. G. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 1983, 303, 41–44. 31. Bossart-Whitaker, P.; Carson, M.; Babu, Y. S.; Smith, C. D.; Laver, W. G.; Air, G. M. Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. J. Mol. Biol. 1993, 232, 1069–1083. 32. von Itzstein, M.; Wu, W. Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Van Phan, T.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993, 363, 418–423. 33. Holzer, C. T.; von Itzstein, M.; Jin, B.; Pegg, M. S.; Stewart, W. P.; Stewart, W. P.; Wu, W. Y. Inhibition of sialidases from viral, bacterial and mammalian sources by analogues of 2-deoxy-2,3-didehydro-N-acetyl neuraminic acid modified at the C-4 position. Glycoconjugate J. 1993, 10, 40–44. 34. Woods, J. M.; Bethell, R. C.; Coates, J. A.; Healy, N.; Hiscox, S. A.; Pearson, B. A.; Ryan, D. M.; Ticehurst, J.; Tilling, J.; Walcott, S. M.; Penn, C. R. 4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetyl neuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro. Antimicrob. Agents Chemother. 1993, 37, 1473–1479. 35. Andrews, D. M.; Cherry, P. C.; Humber, D. C.; Jones, P. S.; Keeling, S. P.; Martin, P. F.; Shaw, C. D.; Swanson, S. Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino-Neu5Ac2en (zanamivir) modified in the glycerol side-chain. Eur. J. Med. Chem. 1999, 34, 563–574. 36. Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kobayashi, Y.; Yamashita, M. Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives. Bioorg. Med. Chem. Lett. 2002, 12, 1921–1924. 37. Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kaneko, S.; Yamashita, M. Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir. Bioorg. Med. Chem. Lett. 2002, 12, 1925–1928. 38. Honda, T.; Kubo, S.; Masuda, T.; Arai, M.; Kobayashi, Y.; Yamashita, M. Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en. Bioorg. Med. Chem. Lett. 2009, 19, 2938–2940. 39. Yamashita, M.; Tomozawa, T.; Kakuta, M.; Tokumitsu, A.; Nasu, H.; Kubo, S. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob. Agents Chemother. 2009, 53, 186–192. 40. Kubo, S.; Tomozawa, T.; Kakuta, M.; Tokumitsu, A.; Yamashita, M. Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration. Antimicrob. Agents Chemother. 2010, 54, 1256–1264. 41. Ishizuka, H.; Yoshiba, S.; Okabe, H.; Yoshihara, K. Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers. J. Clin. Pharmacol. 2010, 50, 1319–1329. 42. Macdonald, S. J.; Watson, K. G.; Cameron, R.; Chalmers, D. K.; Demaine, D. A.; Fenton, R. J.; Gower, D.; Hamblin, J. N.; Hamilton, S.; Hart, G. J.; Inglis, G. G.; Jin, B.; Jones, H. T.; McConnell, D. B.; Mason, A. M.; Nguyen, V.; Owens, I. J.; Parry, N.; Reece, P. A.; Shanahan, S. E.; Smith, D.; Wu, W. Y.; Tucker, S. P. Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are effective at a once-weekly dosing regimen. Antimicrob. Agents Chemother. 2004, 48, 4542–4549. 43. Macdonald, S. J.; Cameron, R.; Demaine, D. A.; Fenton, R. J.; Foster, G.; Gower, D.; Hamblin, J. N.; Hamilton, S.; Hart, G. J.; Hill, A. P.; Inglis, G. G.; Jin, B.; Jones, H. T.; McConnell, D. B.; McKimm-Breschkin, J.; Mills, G.; Nguyen, V.; Owens, I. J.; Parry, N.; Shanahan, S. E.; Smith, D.; Watson, K. G.; Wu, W. Y.; Tucker, S. P. Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza. J. Med. Chem. 2005, 48, 2964–2971. 44. Kim, C. U.; Lew, W.; Williams, M. A.; Liu, H.; Zhang, L.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai, C. Y.; Laver, W. G.; Stevens, R. C. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J. Am. Chem. Soc. 1997, 119, 681–690. 45. Li, W.; Escarpe, P. A.; Eisenberg, E. J.; Cundy, K. C.; Sweet, C.; Jakeman, K. J.; Merson, J.; Lew, W.; Williams, M.; Zhang, L.; Kim, C. U.; Bischofberger, N.; Chen, M. S.; Mendel, D. B. Identification of GS4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS4071. Antimicrob. Agents Chemother. 1998, 42, 647–653. 46. Sidwell, R. W.; Huffman, J. H.; Barnard, D. L.; Bailey, K. W.; Wong, M. H.; Morrison, A.; Syndergaard, T.; Kim, C. U. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral Res. 1998, 37, 107–120. 47. Sweeny, D. J.; Lynch, G.; Bidgood, A. M.; Lew, W.; Wang, K. Y.; Cundy, K. C. Metabolism of the influenza neuraminidase inhibitor prodrug oseltamivir in the rat. Drug Metab. Dispos. 2000, 28, 737–741. 48. Yamamoto, T.; Kumaxawa, H.; Inami, K.; Teshima, T.; Shiba, T. Syntheses of sialic acid isomers with inhibitory activity against neuraminidase. Tetrahedron Lett. 1992, 33, 5791–5794. 49. Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T. H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. L.; Laver, G.W.; Montgomery, J. A. BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. J. Med. Chem. 2000, 43, 3482–3486. 50. Russell, R. J.; Haire, L. F.; Stevens, D. J.; Collins, P. J.; Lin, Y. P.; Blackburn, G. M.; Hay, A. J.; Gamblin, S. J.; Skehel, J. J. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 2006, 443, 45–49. 51. Collins, P. J.; Haire, L. F.; Lin, Y. P.; Liu, J. F.; Russell, R. J.; Walker, P. A.; Skehel, J. J.; Martin, S. R.; Hay, A. J.; Gamblin, S. J. Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Nature 2008, 453, 1258–1261. 52. Dharan, N. J.; Gubareva, L. V.; Meyer, J. J.; Okomo-Adhiambo, M.; McClinton, R. C.; Marshall, S. A.; St. George, K.; Epperson, S.; Brammer, L.; Klimov, A. I.; Bresee, J. S.; Fry, A. M. Oseltamivir-resistance working group. Infections with oseltamivir-resistant influenza A (H1N1) virus in the United States. JAMA 2009, 301, 1034–1041. 53. Schug, K. A.; Lindner, W. Noncovalent binding between guanidinium and anionic groups: focus on biological- and synthetic-based arginine/guanidinium interactions with phosph[on]ate and sulf[on]ate residues. Chem. Rev. 2005, 105, 67−113. 54. Shie, J. J.; Fang, J. M.; Wang, S. Y.; Tsai, K. C.; Cheng, Y. S.; Yang, A. S.; Hsiao, S. C.; Su, C. Y.; Wong, C. H. Synthesis of Tamiflu and its phosphonate congeners possessing potent anti-influenza activity. J. Am. Chem. Soc. 2007, 129, 11892–11893. 55. Cheng, Y. C.; Prusoff, W. H. Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099–3108. 56. Rohloff, J. C.; Kent, K. M.; Postich, M. J.; Becker, M. W.; Chapman, H. H.; Kelly, D. E.; Lew, W.; Louie, M. S.; McGee, L. R.; Prisbe, E. J.; Schultze, L. M.; Yu, R. H.; Zhang, L. Practical total synthesis of the anti-influenza drug GS-4104. J. Org. Chem. 1998, 63, 4545–4550. 57. Federspiel, M.; Fischer, R.; Hennig, M.; Mair, H. J.; Oberhauser, T.; Rimmler, G.; Albiez, T.; Bruhin, J.; Estermann, H.; Gandert, C.; Göckel, V.; Götzö, S.; Hoffmann, U.; Huber, G.; Janatsch, G.; Lauper, S.; Röckel-Stäbler, O.; Trussardi, R.; Zwahlen, A. G. Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64-0796/002, GS-4104-02): ethyl (3R,4S,5S)-4,5- epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate. Org. Proc. Res. Dev. 1999, 3, 266–274. 58. Karpf, M.; Trussardi, R. New, azide-free transformation of epoxides into 1,2-diamino compounds: synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu). J. Org. Chem. 2001, 66, 2044–2051. 59. Karpf, M.; Trussardi, R. Efficient access to oseltamivir phosphate (Tamiflu) via the O-trimesylate of shikimic acid ethyl ester. Angew. Chem. Int. Ed. 2009, 48, 5760–5762. 60. Nie, L. D.; Shi, X. X.; Ko, K. H.; Lu, W. D. A short and practical synthesis of oseltamivir phosphate (tamiflu) from (–)-shikimic acid. J. Org. Chem. 2009, 74, 3970–3973. 61. Nie, L. D.; Shi, X. X.; Quan, N.; Wang, F. F.; Lu, X. Novel asymmetric synthesis of oseltamivir phosphate (Tamiflu) from (–)-shikimic acid via cyclic sulfite intermediates. Tetrahedron: Asymmetry 2011, 22, 1692–1699. 62. Nie, L. D.; Ding, W.; Shi, X. X.; Quan, N.; Lu, X. A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (–)-shikimic acid. Tetrahedron: Asymmetry 2012, 23, 742–747. 63. Kim, H. K.; Park, K. J. J. A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (–)-shikimic acid. Tetrahedron Lett. 2012, 53, 1561–1563. 64. Albert, R.; Dax, K.; Link, R. W.; Stütz, A. E. Carbohydrate triflates: reaction with nitrite, leading directly to epi-hydroxy compounds. Carbohydr. Res. 1983, 118, C5–C6. 65. Osato, H.; Jones, I. L.; Chen, A.; Chai, C. L. L. Efficient formal synthesis of oseltamivir phosphate (Tamiflu) with inexpensive D-ribose as the starting material. Org. Lett. 2010, 12, 60–63. 66. Bernet, B.; Vasella, A. Carbocyclische verbindungen aus monosacchariden. I. umsetzungen in der glucosereihe. Helv. Chim. Acta 1979, 62, 1990–2016. 67. Nakane, M.; Hutchinson, C. R.; Gollman, H. A convenient and general synthesis of 5-vinylhexofuranosides from 6-halo-6-deoxypyranosides. Tetrahedron Lett. 1980, 21, 1213–1216. 68. Fürstner, A.; Jumbam, D.; Teslic, J.; Weidmann, H. Metal-graphitereagents in carbohydrate chemistry. 8. The scope and limitations of the use of zinc/silver-graphite in the synthesis of carbohydrate-derived substituted hex-5-enals and pent-4-enals. J. Org. Chem. 1991, 56, 2213–2217. 69. Wichienukul, P.; Akkarasamiyo, S.; Kongkathip, N.; Kongkathip, B. An efficient synthesis of oseltamivir phosphate (Tamiflu) via a metal-mediated domino reaction and ring-closing metathesis. Tetrahedron Lett. 2010, 51, 3208–3210. 70. Shangguan, N.; Katukojvala, S.; Greenberg, R.; Williams, L. J. The reaction of thio acids with azides: a new mechanism and new synthetic applications. J. Am. Chem. Soc. 2003, 125, 7754–7755. 71. Ma, J.; Zhao, Y.; Ng, S.; Zhang, J.; Zeng, J.; Than, A.; Chen, P.; Liu, X. W. Sugar-based synthesis of Tamiflu and its inhibitory effects on cell secretion. Chem. Eur. J. 2010, 16, 4533–4540. 72. Ko, J. S.; Keum, J. E.; Ko, S. Y. A synthesis of oseltamivir (Tamiflu) starting from D-mannitol. J. Org. Chem. 2010, 75, 7006–7009. 73. Mandai, T.; Oshitari, T. Synthesis of oseltamivir from D-mannitol. Synlett 2009, 5, 783–786. 74. Weng, J.; Li, Y. B.; Wang, R. B.; Li, F. Q.; Liu, C.; Chan, A. S.; Lu, G. A practical and azide-free synthetic approach to oseltamivir from diethyl D-tartrate. J. Org. Chem. 2010, 75, 3125–3128. 75. Ishikawa, H.; Suzuki, T.; Hayashi, Y. High-yielding synthesis of the anti-influenza neuramidase inhibitor (–)-oseltamivir by three “one-pot” operations. Angew. Chem. Int. Ed. 2009, 48, 1304–1307. 76. Chen, C. A.; Fang, J. M. Synthesis of oseltamivir and tamiphosphor from N-acetyl-D-glucosamine. Org. Biomol. Chem. 2013, 11, 7687–7699. 77. Shie, J. J.; Fang, J. M.; Wong, C. H. A concise and flexible synthesis of the potent anti-influenza agents Tamiflu and tamiphosphor. Angew. Chem. Int. Ed. 2008, 47, 5788–5791. 78. Sullivan, B.; Carrera, I.; Drouin, M.; Hudlicky, T. Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (Tamiflu) from ethyl benzoate. Angew. Chem. Int. Ed. 2009, 48, 4229–4231. 79. Werner, L.; Machara, A.; Hudlicky, T. Short chemoenzymatic azide-free synthesis of oseltamivir (Tamiflu): approaching the potential for process efficiency. Adv. Synth. Catal. 2010, 352, 195–200. 80. Yamatsugu, K.; Yin, L.; Kamijo, S.; Kimura, Y.; Kanai, M.; Shibasaki, M. A synthesis of Tamiflu by using a barium-catalyzed asymmetric Diels–Alder-type reaction. Angew. Chem. Int. Ed. 2009, 48, 1070–1076. 81. Werner, L.; Machara, A.; Sullivan, B.; Carrera, I.; Moser, M.; Adams, D. R.; Hudlicky, T. Several generations of chemoenzymatic synthesis of oseltamivir (Tamiflu): evolution of strategy, quest for a process-quality synthesis, and evaluation of efficiency metrics. J. Org. Chem. 2011, 76, 10050−10067. 82. Alagiri, K.; Furutachi, M.; Yamatsugu, K.; Kumagai, N.; Watanabe, T.; Shibasaki, M. Two approaches toward the formal total synthesis of oseltamivir phosphate (Tamiflu): catalytic enantioselective three-component reaction strategy and L-glutamic acid strategy. J. Org. Chem. 2013, 78, 4019–4026. 83. Yeung, Y. Y.; Hong, S.; Corey, E. J. A short enantioselective pathway for the synthesis of the anti-influenza neuramidase inhibitor oseltamivir from 1,3-butadiene and acrylic acid. J. Am. Chem. Soc. 2006, 128, 6310–6311. 84. Abrecht, S.; Harrington, P.; Iding, H.; Karpf, M.; Trussardi, R.; Wirz, B.; Zutter, U. The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu): a challenge for synthesis & process research. Chimia 2004, 58, 621–629. 85. Yamatsugu, K.; Kamijo, S.; Suto, Y.; Kanai, M.; Shibasaki, M. A concise synthesis of tamiflu: third generation route via the Diels–Alder reaction and the Curtius rearrangement. Tetrahedron Lett. 2007, 48, 1403–1406. 86. Albright, J. D.; Goldman, L. Dimethyl sulfoxide-acid anhydride mixtures for the oxidation of alcohols. J. Am. Chem. Soc. 1967, 89, 2416–2423. 87. Satoh, N.; Akiba, T.; Yokoshima, S.; Fukuyama, T. A practical synthesis of (–)-oseltamivir. Angew. Chem. Int. Ed. 2007, 46, 5734–5736. 88. Satoh, N.; Akiba, T.; Yokoshima, S.; Fukuyama, T. A practical synthesis of (–)-oseltamivir. Tetrahedron 2009, 65, 3239–3245. 89. Ishikawa, H.; Suzuki, T.; Orita, H.; Uchimaru, T.; Hayashi, Y. High-yielding synthesis of the anti-influenza neuraminidase inhibitor (–)-oseltamivir by two “one-pot” sequences. Chem. Eur. J. 2010, 16, 12616–12626. 90. Ishikawa, H.; Bondzic, B. P.; Hayashi, Y. Synthesis of (–)-oseltamivir by using a microreactor in the Curtius rearrangement. Eur. J. Org. Chem. 2011, 30, 6020–6031. 91. Zhu, S. L.; Yu, S. Y.; Wang, Y.; Ma, D. W. Organocatalytic Michael addition of aldehydes to protected 2-amino-1-nitroethenes: the practical syntheses of oseltamivir (Tamiflu) and substituted 3-aminopyrrolidines. Angew. Chem. Int. Ed. 2010, 49, 4656–4660. 92. Weng, J.; Li, Y. B.; Wang, R. B.; Lu, G. Organocatalytic Michael reaction of nitroenamine derivatives with aldehydes: short and efficient asymmetric synthesis of (–)-oseltamivir. ChemCatChem 2012, 4, 1007–1012. 93. Mukaiyama, T.; Ishikawa, H.; Koshino, H.; Hayashi, Y. One-pot synthesis of (–)-oseltamivir and mechanistic insights into the organocatalyzed Michael reaction. Chem. Eur. J. 2013, 19, 17789–17800. 94. Fukuta, Y.; Mita, T.; Fukuda, N.; Kanai, M.; Shibasaki, M. De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3. J. Am. Chem. Soc. 2006, 128, 6312–6313. 95. Trost, B. M.; Zhang, T. A concise synthesis of (–)-oseltamivir. Angew. Chem. Int. Ed. 2008, 47, 3759–3761. 96. Trost, B. M.; Massiot, G. S. New synthetic reactions. A chemoselective approach to cleavage α to a carbonyl group via β-keto sulfides. Preparation of 1,2-diketones. J. Am. Chem. Soc. 1977, 99, 4405–4412. 97. Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. Expanding the scope of C–H amination through catalyst design. J. Am. Chem. Soc. 2004, 126, 15378–15379. 98. Fiori, K. W.; Du Bois, J. Catalytic intermolecular amination of C–H bonds: method development and mechanistic insights. J. Am. Chem. Soc. 2007, 129, 562–568. 99. Zutter, U.; Iding, H.; Spurr, P.; Wirz, B. New, efficient synthesis of oseltamivir phosphate (Tamiflu) via enzymatic desymmetrization of a meso-1,3- cyclohexanedicarboxylic acid diester. J. Org. Chem. 2008, 73, 4895–4902. 100. Poly, W.; Schomburg, D.; Hoffmann, H. M. R. Stereoselective generation and facile dimerization of (E)-2-methylene-3-alkenoic acid esters. J. Org. Chem. 1988, 53, 3701–3710. 101. Hoffmann, H. M. R. 1,4-Diazobicyclo [2.2.2]octane-catalyzed coupling of aldehydes and activated double bonds. Part 3. A short and practical synthesis of mikanecic acid (4-vinyl-1-cyclohexene-1,4-dicarboxylic acid). Helv. Chim. Acta 1984, 67, 413–415. 102. Yang, W.; Koreeda, M. The stereocontrolled synthesis of phthalic acid 4,5-cis-dihydrodiol. An unambiguous structural assignment of the bacterial metabolite of phthalic acid. J. Org. Chem. 1992, 57, 3836–3839. 103. Evans, D. A. Studies in asymmetric synthesis. The development of practical chiral enolate synthons. Aldrichim. Acta 1982, 15, 23–32. 104. Evans, D. A.; Britton, T. C.; Ellman, J. A. Contrasteric carboximide hydrolysis with lithium hydroperoxide. Tetrahedron Lett. 1987, 28, 6141–6144. 105. Xu, S.; Chen, R.; Qin, Z.; Wu, G.; He, Z. Divergent amine-catalyzed [4+2] annulation of Morita–Baylis–Hillman allylic acetates with electron-deficient alkenes. Org. Lett. 2012, 14, 996–999. 106. Ding, H.; Zhang, Y.; Bian, M.; Yao, W.; Ma, C. Concise assembly of highly substituted furan-fused 1,4-thiazepines and their Diels–Alder reactions with benzynes. J. Org. Chem. 2008, 73, 578–584. 107. Martinelli, M. J. Asymmetric Diels–Alder reactions with γ-functionalized α,β-unsaturated chiral N-acyloxazolidinones: synthesis of (+)-S-145. J. Org. Chem. 1990, 55, 5065–5073. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59153 | - |
| dc.description.abstract | 流行性感冒是一種嚴重的急性呼吸道感染，長期威脅人類健康，克流感是在臨床上用來有效治療流感的藥物之一。狄爾斯–阿爾德反應是在有機合成化學上最有效轉換的反應之一，因為其不只可以在一個步驟建構兩個新的碳–碳單鍵，更可以形成四個連續的立體中心，並有很好的位置和立體選擇性。因此化學家利用狄爾斯–阿爾德反應來建構克流感主要的環己烯結構。
我們成功合成出新穎的二烯前驅物214，此溴化合物214在鹼性條件下生成共軛二烯，其同時具有推電子的3-戊烷氧基與拉電子的羧基，容易進行二聚化反應。若加入活性好的烯烴，則可以成功捕捉二烯中間產物，進行狄爾斯–阿爾德反應。尤其利用反丁烯二酸雙烷基酯263捕捉二烯，可以得到預期的狄爾斯–阿爾德反應的產物264。我們利用雙羧酸化合物243形成醯基疊氮的衍生物，並經Curtius重排反應，成功得到克流感的前驅物250b (外消旋混合物)，將兩個非鏡像異構物成功分離的關鍵步驟在於進行單一第三丁氧羰基的保護，得到均為反向的化合物249b。 根據之前的方法進一步成功合成出反丁烯二酸雙烷基酯269其接上由Evans團隊開發的手性輔助劑惡唑烷酮，溴化合物214在鹼性條件下與手性反丁烯二酸雙烷基酯269進行不對稱狄爾斯–阿爾德反應，得到兩個異構物271和272其比例為60:40，可惜的是嘗試水解手性惡唑烷酮並沒有成功。未來我們將利用反丁烯二酸雙烷基酯接上含(–)-麻黃素衍生之手性硫醇當作親二烯，希望狄爾斯–阿爾德反應的產物其硫醇基團將來可以容易被水解。 | zh_TW |
| dc.description.abstract | Influenza is a severe health problem to cause serious acute respiratory infection and endanger humans for a long time. Oseltamivir is one of the effective anti-influenza drugs in clinical use. Diels–Alder reaction is one of the most powerful transformations in synthetic organic chemistry. Not only does this strategy construct two new C–C σ-bonds in one step, but it also forms a cyclohexene system up to four contiguous stereocenters with good regio- and stereoselectivity. Therefore, many chemists have developed the methods using Diels–Alder reactions to construct the cyclohexene core structure of oseltamivir.
We synthesized a novel diene precursor 214. Under basic conditions, the bromo compound 214 formed a conjugated diene, which bears both electron-donating 3-pentoxy and electron-withdrawing carboxy substituents. This diene intermediate easily underwent dimerization, but was trapped in situ with activated alkenes, particularly dialkyl fumarate 263 to afford the desired Diels–Alder adduct 264. Using this method, dicarboxylic acid 243 was successfully applied to synthesize an oseltamivir precursor 250b (in racemic mixture) via a sequence of reactions that comprise acyl azide formation and Curtius rearrangement. A key step was to separate the mono-Boc protected all-trans compound 249b from its diastereomer. As an approach to obtain the optically active oseltamivir, further synthesized the fumarate 269 with chiral oxazolidinone, which is a chiral auxiliary initially developed in Evans’ group. The asymmetric Diels–Alder reaction of bromo compound 214 with chiral fumarate 269 under basic condition afforded a mixture of two isomers 271 and 272 in a ratio of 60:40. Unfortunately, attempts to hydrolyze the chiral oxazolidinone products failed. In the future, we will investigate a fumarate dienophile with the chiral thiol auxiliary derived from (–)-ephedrine. Hopefully, hydrolysis of the thioester moiety in the Diels–Alder product will be easily carried out. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T09:16:51Z (GMT). No. of bitstreams: 1 ntu-106-D99223108-1.pdf: 19070701 bytes, checksum: 093a1c5a2771972234d1ca54e4d09d6a (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 謝誌 I
中文摘要 III Abstract V 目錄 VII 表目錄 IX 圖目錄 XI 流程目錄 XII 簡稱用語對照表 XIV 第一章 緒論 1 第一節 流行性感冒 1 第二節 流感病毒簡介 4 第三節 病毒表面重要的膜蛋白 6 3-1 血液凝集素(Hemagglutinin, HA) 6 3-2 神經胺酸酶(Neuraminidase, NA) 8 3-3 M2 (Matrix 2)離子通道蛋白 8 第四節 流感病毒的生命週期 10 第五節 抗流感藥物的開發 12 5-1 M2離子通道蛋白抑制劑 12 5-2 神經胺酸酶抑制劑 13 5-2-1 瑞樂沙(RelenzaTM)的開發 15 5-2-2 克流感(TamifluTM)的開發 19 5-2-3 Peramivir (RapivabTM)的開發 22 5-3 抗藥性問題 23 5-4 零流感(Tamiphosphor)的開發 24 第六節 克流感的合成 27 6-1 以天然物合成克流感 27 6-2 經由Diels–Alder反應合成克流感 44 6-3 以一鍋化合成克流感 50 6-4 其他方法合成克流感 54 第二章 結果與討論 59 第一節 以Diels–Alder反應合成克流感 59 1-1 新的克流感合成路徑分析 59 1-2 製備親二烯200與二烯化合物201 59 1-3 以含溴化合物214進行Diels–Alder反應 64 1-4 嘗試以親二烯200和231與二烯化合物進行Diels–Alder反應 71 第二節 改良原先合成克流感之路徑 76 2-1 以Diels–Alder產物242合成克流感之路徑 76 2-2 以Diels–Alder產物228合成克流感之路徑 84 2-3 以Diels–Alder產物243合成克流感之路徑 90 2-4 以Diels–Alder產物264合成克流感之路徑 91 第三節 以不對稱Diels–Alder反應合成克流感 96 第四節 結論 105 第三章 實驗部分 111 第一節 一般說明 111 第二節 化學合成步驟以及結構鑑定 113 第四章 參考文獻 161 附錄 化合物之核磁共振光譜與X-ray ORTEP圖 179 | |
| dc.language.iso | zh-TW | |
| dc.title | "由具有2-羧基與4-烷氧基取代之1,3-丁二烯進行狄爾斯–阿爾德反應以合成克流感" | zh_TW |
| dc.title | Synthesis of Oseltamivir Using Diels–Alder Reaction
of 1,3-Butadiene Bearing 2-Carboxy and 4-Alkoxy Substituents | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 羅禮強(Lee-Chiang Lo),汪根欉(Ken-Tsung Wong),王宗興(Tsung-Shing Andrew Wang),陳焜銘(Kwun-min Chen),簡敦誠(Tun-Cheng Chien) | |
| dc.subject.keyword | 克流感,狄爾斯–阿爾德反應,丁二烯, | zh_TW |
| dc.subject.keyword | Oseltamivir,Tamiflu,Diels–Alder Reaction,Butadiene, | en |
| dc.relation.page | 268 | |
| dc.identifier.doi | 10.6342/NTU201701533 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-07-13 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 目前未授權公開取用 | 18.62 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。