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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54952完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 忻凌偉 | |
| dc.contributor.author | Chun-Yi Wang | en |
| dc.contributor.author | 王鈞毅 | zh_TW |
| dc.date.accessioned | 2021-06-16T03:42:30Z | - |
| dc.date.available | 2020-03-12 | |
| dc.date.copyright | 2015-03-12 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-02-11 | |
| dc.identifier.citation | 1. Iversen, L. L. Dopamine handbook. Oxford : Oxford University Press, NY, 2010. 2. Andrew, B. B.; S oslash;vik1, E.; Cornish, J. L. The roles of dopamine and related compounds in reward-seeking behavior across animal phyla. Front. Behav. Neurosci. 2010, 4, 1-9. 3. Rub iacute;, B.; Maechler, P. Minireview: new roles for peripheral dopamine on metabolic control and tumor growth: let’s seek the balance. Endocrinology. 2010, 151, 5570-5581. 4. Hyman, S. E.; Malenka, R. C.; Nestler, E. J. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu. Rev. Neurosci. 2006, 29, 565-598. 5. Eisenhofer, G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacology therapeutics. 2001, 91, 35-62. 6. Torres, G. E.; Gainetdinov, R. R. Caron, M. G. Plasma membrane monoamine transporters: structure, regulation and function. Nature Reviews Neuroscience. 2003, 4, 13-25. 7. Okunola-Bakare, O. M.; Cao, J.; Kopajtic, T.; Katz, J. L.; Loland, C. J.; Shi, L.; Newman, A. H. Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl) sulfinyl] acetamide (Modafinil) Analogues. J. Med. Chem. 2014, 57, 1000−1013. 8. Berger, P.; Janowsky, A.; Vocci, F.; Skolnick, P.; Schweri, M. M.; Paul, S. M. GBR-12935: A specific high affinity ligand for labeling the dopamine transport complex. European journal of pharmacology. 1985, 107, 289-290. 9. Andersen, P. H. Biochemical and pharmacological characterization of [3H] GBR 12935 binding in vitro to rat striatal membranes: labeling of the dopamine uptake complex. Journal of neurochemistry. 1987, 48, 1887-1896. 10. Norl eacute;n, M.; Allard, P. Reduction in number of dopamine uptake sites but unchanged number of piperazine-acceptor/CYP450IID6 binding sites in the human caudate nucleus in aging. Neuroscience letters. 1996, 209, 161-164. 11. Reith, M. E. Neurotransmitter Transporters: Structure, Function, and Regulation. Humana Press, 2002. 12. Pimlott, S. L.; Sutherland, A. Molecular tracers for the PET and SPECT imaging of disease. Chem. Soc. Rev. 2011, 40, 149-162. 13. Ametamey, S. M.; Honer, M.; Schubiger, P. A. Molecular imaging with PET. Chem. Rev. 2008,108, 1501-1516. 14. Cai, L.; Lu, S.; Pike, V. W. Chemistry with [18F] fluoride ion. Eur. J. Org. Chem. 2008, 2853-2873. 15. Chun, J. H.; Lu, S.; Lee, Y. S.; Pike, V. W. Fast and high-yield microreactor syntheses of ortho- substituted [18F] fluoroarenes from reactions of [18F] fluoride ion with diaryliodonium salts. J. Org. Chem. 2010, 75, 3332-3338. 16. Jalalian, N. Development and Applications of Hypervalent Iodine Compounds : Powerful Arylation and Oxidation Reagents, Stockholm university, 2012. 17. Wirth, T. Hypervalent Iodine Chemistry: Modern Developments in Organic Synthesis, Springer, 2003. 18. Merritt, E. A.; Olofsson, B. Diaryliodonium salts: A journey from obscurity to fame. Angew. Chem. Int. Ed. 2009, 48, 9052-9070. 19. Pike, V.; Widdowson, D. Facile synthesis of substituted diaryliodonium tosylates by treatment of aryltributylstannanes with Koser’s reagent. J. Chem. Soc., Perkin Trans. 1. 1999, 3, 245-248. 20. Landge, K. P.; Jang, K. S.; Lee, S. Y.; Chi, D. Y. Approach to the Synthesis of Indoline Derivatives from Diaryliodonium Salts. J. Org. Chem. 2012, 77, 5705-5713. 21. Kamierczak, P.; Skulski, L. A Short-Cut Synthesis of Diaryliodonium Bromides Followed by Oxidative Anion Metatheses. Synthesis. 1995, 8, 1027-1032. 22. Bielawski, M.; Aili, D.; Olofsson, B. Regiospecific one-pot synthesis of diaryliodonium tetrafluoroborates from arylboronic acids and aryl iodides. J. Org. Chem. 2008, 73, 4602-4607. 23. 張莉德，國立台灣大學醫學院藥學研究所博士論文，101年3 月，Part 1: Synthesis and Monoamine Transporter Activity of Fluoro-Substituted GBR12909 and GBR12935 Derivatives. 24. Tredwell, M.; Gouverneur, V. 18F Labeling of Arenes. Angew. Chem. Int. Ed. 2012, 51, 11426-11437. 25. Nicolaou, K. C.; Becker, J.; Lim, Y. H.; Lemire, A.; Neubauer, T.; Montero, A. Total synthesis and biological evaluation of (+)-and (−)- bisanthraquinone antibiotic BE-43472B and related compounds. J. Am. Chem. Soc. 2009. 131, 14812-14826. 26. Telu, S.; Chun, J. H.; Sim eacute;on, F. G.; Lu, S.; Pike, V. W. Syntheses of mGluR5 PET radioligands through the radiofluorination of diaryliodonium tosylates. Org. Biomol. Chem. 2011, 9, 6629-6638. 27. Moon, B. S.; Kil, H. S.; Park, J. H.; Kim, J. S.; Park, J.; Chi, D. Y.; Kim, S. E. Facile aromatic radiofluorination of [18 F] flumazenil from diaryliodonium salts with evaluation of their stability and selectivity. Org. Biomol. Chem. 2011, 9, 8346-8355. 28. Wang, B.; Cerny, R. L.; Uppaluri, S.; Kempinger, J. J.; DiMagno, S. G. Fluoride-promoted ligand exchange in diaryliodonium salts. Journal of fluorine chemistry. 2010, 131, 1113-1121. 29. Kosugi, M.; Ohya, T.; Migita, T. Preparation of aryltributyltin having electron-withdrawing group by palladium catalyzed reaction of hexabutylditin with aryl iodide. Bul. Chem. Soc. Jpn. 1983, 56, 3855-3856. 30. Chun, J. H.; Pike, V. W. Regiospecific syntheses of functionalized diaryliodonium tosylates via [hydroxy (tosyloxy) iodo] arenes generated in situ from (diacetoxyiodo) arenes. J. Org. Chem. 2012, 77, 1931-1938. 31. Denton, J. J.; Lawson, V. A.; Neier, W. B.; Turner, R. J. Antispasmodics. II. Tertiary β-Amino Alcohols. J. Am. Chem. Soc. 1949, 71, 2050-2052. 32. Palle, J.; Anders, K.; Marie, L. J. Propanolamine derivatives, their preparation and use. EP0576766 (A1), 1994. 33. Lewis, D.; Zhang, Y.; Prisinzano, T.; Dersch, C. M.; Rothman, R. B.; Jacobson, A. E.; Rice, K. C. Further exploration of 1-{2-[Bis-(4-fluorophenyl) methoxy] ethyl} piperazine (GBR 12909): role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter. Bioorg. Med. Chem. Lett. 2003, 13, 1385-1389. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54952 | - |
| dc.description.abstract | 先前本實驗室以GBR12935為先導化合物，發展出對多巴胺轉運體具有高度的結合力、選擇性和適當脂溶性之化合物LTC-844。為合成 [18F]-LTC-844並應用於正子斷層掃描，必需設計出穩定且易於進行18F標記反應的前驅物。因diaryliodonium salts具有缺電子和良好的離去基性質，可與多種親核基進行取代反應。本研究嘗試以arylstannanes與不同的[hydroxyl(tosyloxy)iodo]arenes (HTIA)反應，合成具有不同取代基的diaryliodonium salts做為進行18F標記反應之前驅物。
為探討含有羥基或鹼性氮原子基團之化合物，對以diaryliodonium salts進行氟化反應的影響，首先合成一系列雙芳香環碘對甲基苯磺酸鹽化合物 (6-8, 15-16, 30, 32-33) 進行氟化反應之模型研究。具有鹼性氮原子基團之化合物，藉由先添加對甲基苯磺酸形成鹽類，可避免鹼性氮原子和HTIA中間體產生副反應，進而大幅提高產率及純度。Aryl group為2-thienyl group與4-methoxyphenyl group的前驅物可得到相似含量的氟化產物，但以aryl group為2-thienyl group之前驅物有較高的氟化選擇性。而放射化學合成反應的結果，以前驅物46最具有潛力，得到最高的放射化學產率，1.8% (EOS)。以[18F]-49進行大鼠的microPET造影，在紋狀體有明顯的選擇性吸收且具有良好的清除率，由這些數據顯示[18F]-49具有潛力發展為多巴胺轉運體之正子斷層影像劑。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T03:42:30Z (GMT). No. of bitstreams: 1 ntu-104-R01423028-1.pdf: 8230355 bytes, checksum: c4cd9e8f6ba2f53c6d10e5a06b7691e0 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書 I 致謝 II 摘要 III Abstract IV 英文縮寫表 VI 目錄 VIII 圖目錄 X 表目錄 X 路徑目錄 XI 1. 緒論 1 1.1 多巴胺轉運體之研究 1 1.2 正子斷層掃描之原理及應用 3 1.3 雙芳香環碘鹽之研究 5 1.4 研究動機與目的 7 2 結果與討論 9 2.1 模型研究之化合物設計 9 2.1.1 化合物6-8, 15-16 之合成 9 2.1.2 化合物6-8, 15-16之氟化反應 11 2.1.3 合成帶有鹼性氮原子之化合物31,34-35 13 2.1.4 化合物31, 34-35之氟化反應 16 2.2 製備氟-18標定之前驅物 18 2.2.1 逆合成分析 18 2.2.2 化合物44-46之合成 19 2.2.3 化合物44-46之氟化反應 21 2.3 放射化學之標定結果 23 2.4 大鼠之正子斷層掃描造影 25 3 結論 27 4 實驗 28 4.1 試劑及溶劑來源 28 4.1.1 市售之試劑及溶劑 28 4.1.2 自製無水溶劑 30 4.2 一般儀器與方法 31 4.3 合成步驟與數據分析 33 參考文獻 65 附表目錄 69 附圖目錄 69 | |
| dc.language.iso | zh-TW | |
| dc.subject | 雙芳香碘鹽 | zh_TW |
| dc.subject | diaryliodonium salts | en |
| dc.title | 含鹼性氮原子的雙芳香環碘對甲基苯磺酸鹽作為放射合成氟十八標記正子斷層掃描影像劑之前驅物的合成與評估 | zh_TW |
| dc.title | Synthesis and Evaluation of Basic Nitrogen-Containing Diaryliodonium Tosylates as Precursors for Radiosynthesis of 18F-labeled Positron Emission Tomograghy Imaging Agents. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王光昭,陳基旺,梁碧惠 | |
| dc.subject.keyword | 雙芳香碘鹽, | zh_TW |
| dc.subject.keyword | diaryliodonium salts, | en |
| dc.relation.page | 129 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-02-12 | |
| dc.contributor.author-college | 藥學專業學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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