「諾羅病毒」(Norovirus)是一個27–38 nm的「非包膜病毒」，屬於「杯狀病毒科」(Caliciviridae) 「諾羅病毒屬」(Norovirus)，在人類的所有年齡層裡，由「諾羅病毒」所引起之急性腸胃炎極為普遍，在全美爆發的急性腸胃炎大約有50%是由「諾羅病毒」所引起，其中由非細菌所引起的腸胃炎，「諾羅病毒」更占了90%。「諾羅病毒」的傳染力以及發病症狀非常驚人，但目前尚無疫苗可預防也無有效的抗病毒藥物可治療，因此全球對於發展出有效的抗「諾羅病毒」之藥物具急迫性。
本實驗室與義大利「米蘭大學」的Bolognesi 教授團隊合作，設計出有效抗「諾羅病毒」之新型「蘇拉明」衍生物，並利用兩步縮合反應、兩步氫化反應及耦合反應，成功合成出五個新型之「磺酸鈉」衍生物。
藉由核磁共振儀、紅外光光譜儀及高解析質譜儀證實已成功得到「蘇拉明」衍生物，此全合成總共有五個步驟，總產率為46%。並測試其「水溶性」及「脂溶性」，探討其結構對「水溶性」及「脂溶性」的影響，冀其在相同的活性下，能夠更容易進入細胞內，達到提升對抗「諾羅病毒」之更佳效用。

目 錄
中文摘要 ………………………………………...…………………...…… i
英文摘要 …………………………………………...……………...……… ii
謝誌 …………………………………………………...……………...…... iii
目錄 ……………………………………………………...………......…… iv
圖目錄 ……………………………………………...…………….…...….. vi
表目錄 ……………………………………………...…….……….…….. viii
一、 緒論 ………………………………………………………...…….. 1
二、 結果 …………………………………………………..……...…… 6
2-1 合成4-4'-(Carbonylbis[imino-3,1-phenylenecarbonylimino
(4-methy-3,1-phenylene)carbonylimino])bis-1,5-
naphthalenedisulfonic Acid Tetrasodium Salt (8) ................. 6
2-2 利用光譜鑑定「磺酸鈉化合物」3、4、6和7 ............….. 8
2-3 利用光譜鑑定「蘇拉明」衍生物8 .................................. 13
2-4 「磺酸鈉化合物」和「蘇拉明」之
「水溶性」和「脂溶性」測試 ......................................... 15
三、 討論 ………………………………………………………...…… 18
3-1 調整pH值對合成「磺酸鈉化合物」 3、6和8之重要性 .... 18
3-2 合成「蘇拉明」衍生物8選擇三光氣之探討 .................. 19

3-3 合成「硫脲化合物」9之探討 .......................................... 20
3-4 合成不對稱「尿素化合物」15之探討 ............................ 22
四、 結論 ……………………………………………………….......… 26
五、 實驗部分 ……………………………………………………...… 27
六、 參考文獻 ………………………………………………………... 34
七、 光譜 …………………………………………………………...… 41

圖 目 錄
圖1. 電子顯微鏡觀測 「諾羅病毒」 之圖像 ......................................... 1
圖2. 「蘇拉明」與「諾羅病毒」酵素RdRp之作用圖 .......................... 3
圖3. 「蘇拉明」結構圖 ........................................................................... 3
圖4. NF023結構圖 ................................................................................. 4
圖5. NF023與「諾羅病毒」聚合酶交互作用之結構圖 ..................... 5
圖6. NF023與「諾羅病毒」聚合酶交互作用之位置圖 ..................... 5
圖7. 「蘇拉明」衍生物8的全合成 ..................................................... 6
圖8. 「硝基苯化合物」3的IR光譜 .................................................... 9
圖9. 比較「硝基苯化合物」3和「苯胺化合物」4的1H NMR光譜 .. 10
圖10. 比較「苯胺化合物」4和「硝基苯化合物」6的1H NMR光譜 .. 11
圖11. 「硝基苯化合物」6的IR光譜 ................................................... 11
圖12. 比較「硝基苯化合物」6和「苯胺化合物」7的1H NMR光譜 .. 12
圖13. 比較「苯胺化合物」7和「蘇拉明」衍生物8的1H NMR光譜 .. 14
圖14. 比較「苯胺化合物」7和「蘇拉明」衍生物8的13C NMR光譜 .. 14
圖15. 「硫脲化合物」9之結構圖 ........................................................... 20
圖16. 「硫脲化合物」9之合成 ............................................................... 21
圖17. 「異硫氰酸酯」化合物10之質譜圖 ............................................ 22
圖18. 「異硫氰酸酯」化合物10之結構圖 ............................................ 22
圖19. 「尿素化合物」15之合成 ............................................................. 23
圖20. 「二聚化合物」16之結構圖 ......................................................... 24

表 目 錄
表1. 五種「磺酸鈉化合物」和「蘇拉明」的「水溶性」 ....................... 16
表2. 五種「磺酸鈉化合物」和「蘇拉明」的「脂溶性」 ....................... 17
表3. 合成「磺酸鈉化合物」 3、6和8之反應條件 ................................. 18
表4. 合成「硫脲化合物」9之反應條件 ................................................ 21
表5. 合成「尿素化合物」15之反應條件 .............................................. 24
表6. Compound Purity by HPLC ............................................................ 42

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