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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 方俊民(Jim-Ming Fang) | |
| dc.contributor.author | Chun-Lin Chen | en |
| dc.contributor.author | 陳俊霖 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:37:32Z | - |
| dc.date.available | 2006-07-29 | |
| dc.date.copyright | 2006-07-29 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-26 | |
| dc.identifier.citation | 1. (a) WHO. Severe acute respiratory syndrome (SARS). Wkly Epidemiol Rec. 2003, 78, 217.
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P.; Penaranda, S.; Bankamp, B.; Maher, K.; Chen, M.-H.; Tong, S.; Tamin, A.; Lowe, L.; Frace, M.; DeRisi, L. L.; Chen, Q.; Wang, D.; Erdman, D. D.; Peret, T. C. T.; Burns, C.; Ksiazek, T. G.; Rollin, P, E.; Sanchez, A.; Liffick, S.; Holloway, B.; Limor, J.; McCaustland, K.; Melissa O.-R.; Fouchier, R.; Gunther, S.; Osterhaus, A. D. M. E.; Drosten, C.; Pallansch, M. A.; Anderson, L. J.; Bellini, W. J. Science. 2003, 300. 1394—1399, Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome 8. Marra, M. A.; Jnoes, S. J. M.; Astell, C. R.; Holt, R. A.; Brooks- Wilson, A.; Butterfield, Y. S. N.; Khattra, J.; Asano, J. K.; Barber, S. A.; Chan, S. Y.; Cloutier, A.; Coughlin, S. M.; Freeman, D.; Girn, N.; Griffith, O. L.; Leach, S. R.; Mayo, M.; McDonald, H.; Montgomery, S. B.; Pandoh, P. K.; Petrescu, A. S.; Robertson, A. G.; Schein, J. E.; Siddiqui, A.; Smailus, D. E.; Stott, J. M.; Yang, G. 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Journal of Organometallic Chemistry 2003, 680, 100—105, Bromination of Tri(isopropyl)boroxine and Asymmetric Synthesis of (2-cyano-3,3-dimethylcyclopropyl)boronic esters 32. Wityak, J.; Earl, R. A.; Abelman, M. M.; Bethel, Y. B.; Fisher, B. N.; Kauffman, G. S.; Kettner, C. A.; Ma, P.; McMillan, J. L.; Mersinger, L. J.; Pesti, J.; Pierce, M. E.; Rankin, F. W.; Chorvat, R. J.; Confalone, P. N. J. Org. Chem. 1995, 60, 3717—3722, Synthesis of Thrombin Inhibitor DuP714 33. Martichonok, V.; Jones, J. B. J. Am. Soc. Chem. 1996, 118, 5, 950—958, Probing the Specificity of the Serine Proteases Subtilisin Carlsberg and α –Chymotrypsin with Enantiomeric 1-Acetamido Boronic Acids. An Unexpected Reversal of the Normal “L”-Stereoselectivity Preference 34. (a)Jagannathan, S.; Forsyth, T. P.; Kettner, C. A. J.Org.Chem. 2001, 66, 6375—6380, Synthesis of Boronic Acid Analogues of α-Amino Acids by Introdcing Side Chain as Electrophiles (b)Matteson, D. S.; Michnick, T. J.; Willett, R. D.; Patterson, C. D. Organometallics 1989, 8, 726—729, [(1R)-1-Acetamido-3-(methylthio)propyl]boronic Acid and the X-ray Structure of Its Ethylene Glycol Ester 35. Mahajan, A. R.; Dutta, D. K.; Boruah, R. C.; Sandha, J. S. Tetrahedron Letters, 1990, 31, 27, 3943—3944, An Efficient Cleavage and Fries Rearragement of Esters with Aluminum Triiodide 36. (a) Caselli, E.; Danieli, C.; Morandi, S.; Bonfiglio, B.; Forni, A.; Prati, F. Org. Lett. 2003, 5, 25, 4863—4866, (S)-(+)-N- Acetyl phenylglycineboronic Acid: A Chiral Derivatizing Agent for Ee Determination of 1,2-diol (b) Kenworthy, M. N.; Kilburn, J. P.; Taylor, J. K. Org. Lett. 2004, 6, 1, 19—22, Highly Functionalized Organolithium Reagents for Enantiomerically Pure α-Amino Aicd Synthesis (C) Collet, S.; Bauchat, P.; Danion-Bougot, R.; Danion, D. Tetrahedron: Asymmetry 1998, 9, 2121-2131, Stereoselective, Nonracemic Synthesis of ω-borono-α-amino Acids 37. (a) Baggio, R.; Elbaum, D.; Kanyo, Z. F.; Carroll, P. J.; Cavalli, R. C.; Ash, D. E.; Christianson, D. W. J. Am. Soc. Chem. 1997, 119, 8107—8108, Inhibition of Mn2+ 2-Arginase by Borate Leads to the Design of a Transition State Analogue Inhibitor, 2(S)- Amino-6- Boronohexanoic Acid (b) Matt, A. V.; Ehrhardt, C.; Burkhard, P.; Metternich, R.; Walkinshaw, M.; Tapparelli, C. Bioorg. Med. Chem. 2000, 8, 2291—2303, Selective Boron-Containing Thrombin Inhibitors—X-ray Analysis Reveals Surprising Binding Mode 38. Coutts, S. J.; Adams, J.; Krolikowski, D,; Snow, R. J. Tetrahedron Letters 1994, 35, 29, 5109—5112, Two Efficient Methods for the Cleavage of Pinanediol Boronate Esters Yielding the Free Boronic Acids 39. http://www.labmed.org.tw/add/select1.ASP?mno=281 40. Martin, R.; Jones, J. B. Tetrahedron Letters, 1995, 36, 46, 8399—8402, Rational Design and Synthesis of a Highly Effective Transition State Analog Inhibitor of the RTEM-1 β-Lactamase 41. Morandi, F.; Caselli, E.; Morandi, S.; Focia, P. J.; Blazquez, J.; Shoichet, B. K.; Prati, F. J. Am. Soc. Chem. 2003, 125, 685—695, Nanomolar Inhibitors of AmpC β-Lactamase | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32223 | - |
| dc.description.abstract | 西元2002年，廣東省爆發第一起SARS感染病例。短短數個月內，已經造成近千人的死亡，由SARS冠狀病毒引起的死亡率相當高，大約是10%。
我們發現L-苯丙胺酸衍生物擁有高度抗SARS的活性，如果化合物由2-氯基，4-硝基苯胺，L-苯丙胺酸，4-二甲基胺基苯甲酸組成，擁有高度抗SARS活性，IC50的數值是0.06microM。L-苯丙胺酸的硼酸酯衍生物也具有抗SARS活性，目前把硼酸酯類化合物水解得到的硼酸類化合物，用來作對抗SARS的抑制劑。 | zh_TW |
| dc.description.abstract | Severe Acute Respiratory Syndrome (SARS) first occurred in Guandong (China) in November of 2002. In only a few months, nearly 1000 lives were claimed. The fatality rate of SARS coronavirus infection is rather high, estimated to be 10%.
We found the phenylalanine derivatives possessed good inhibitory activities. The compound prepared from 2-chloro-4-nitroaniline, L-phenylalanine, and 4-(dimethylamino)benzoic acid is the most potent inhibitor, showing an IC50 of 0.06 μM. The boronate analog of L-phenylalanine also showed inhibitory activities. We currently conduct the hydrolysis to remove the pinanediol moiety in order to get the boronic acid compounds as the transition state mimics of phenylalinine, and evaluate their anti-SARS activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:37:32Z (GMT). No. of bitstreams: 1 ntu-95-R93223024-1.pdf: 4226405 bytes, checksum: b75b676f425fb2af90935d2ae7a96b5a (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目 錄
目錄………………………………………………………… I 圖目錄……………………………………………………… III 表目錄……………………………………………………… V Scheme目錄………………………………………………… VI 簡稱用語對照表…………………………………………… VIII 中文摘要…………………………………………………… IX 英文摘要…………………………………………………… X 謝誌………………………………………………………… XII 壹、 緒論 1-1. SARS -嚴重急性呼吸道症候群……….……………….1 1-2. SARS病毒的定位………………………………………..3 1-3. SARS病毒感染方式……………………………………..8 1-4. SARS冠狀病毒基因定序………………….……………10 1-5. SARS冠狀病毒主要水解蛋白酶…………….…………13 1-6. 過渡態硼酸酯類化合物……………………………….15 貳、 結果與討論 2-1. 發展背景………………………………………………….21 2-2. 醯替苯胺(Anilide)類型抑制分子…………….……….25 2-3. 化合物的合成-JMF1507衍生物………….….………….28 2-4. 化合物的合成-硼酸酯化合物……………..…….…… 48 2-5. 生物活性檢測結果與結論……………………………… 67 參、 實驗部分 壹. 一般敘述……………………………………….………74 貳. 實驗步驟與光譜數據……………………….…………78 肆、 參考文獻……………………………………………….113 伍、 摘錄之光譜……………………………………… …..123 陸、 附件…………………………………………………….160 ISOR 2006神戶有機化學會議得獎紀錄………………… 161 發表國際期刊之著作J. Med. Chem. 2005, 48, 4469........163 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抑制劑 | zh_TW |
| dc.subject | 冠狀病毒 | zh_TW |
| dc.subject | inhibitor | en |
| dc.subject | SARS | en |
| dc.title | 設計及合成L-苯丙胺酸衍生物對抗SARS-CoV 3CL蛋白酶 | zh_TW |
| dc.title | Synthesis of L-Phenylalanine Derivatives as the Inhibitors against the SARS-CoV 3CL Protease | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡蘊明,李文山 | |
| dc.subject.keyword | 冠狀病毒,抑制劑, | zh_TW |
| dc.subject.keyword | SARS,inhibitor, | en |
| dc.relation.page | 167 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-27 | |
| 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 | |
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