跳到主要內容

簡易檢索 / 詳目顯示

回結果列表
研究生： 王淳逸
Chun-yi Wang
論文名稱： (+)-Aspicilin的合成
Total synthesis of (+)-Aspicilin
指導教授： 侯敦仁
Duen-Ren Hou
口試委員:
學位類別： 碩士
Master
系所名稱： 理學院 - 化學學系
Department of Chemistry
畢業學年度： 99
語文別： 中文
論文頁數： 127
中文關鍵詞： 酯化反應 、環閉合置換 、天然物 、有機合成
外文關鍵詞： total synthesis, RCM, Ring crossing metathesis, aspicilin, esterification
相關次數： 點閱：18  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 利用掌性的雙烯雙醇((3R,4R)-hexa-1,5-diene-3,4-diol)87為起始物合成(+)-Aspicilin。在此我們利用雙烯雙醇87保護後進行Sharpless 環氧化反應，建構出第三個掌性中心。再與丙二酸二乙酯(diethyl malonate)反應得到內酯化合物。接著進行水解反應，形成羧酸化合物，再與具有掌性中心的(S)-十一烯二正十二醇((S)-dodec-11-en-2-ol)進行酯化反應。利用環閉合置換反應，合環得到十八圓環的內酯。以二異丙胺鋰拔掉內酯的α位置氫與苯硒官能基硒化，接著用過氧化氫氧化生成共軛雙鍵，得到天然物(+)-Aspicilin。

    (+)-Aspicilin was synthesized using (3R,4R)-hexa-1,5-diene-3,4-diol as the starting material. We applied Sharpless epoxidation to create the third chirality center. Diethyl malonate was used to attack the epoxide to produce lactone, which was hydrolyzed to give acid. Esterification of acid and (S)-dodec-11-en-2-ol was achieved by Yamaguchi esterification. Ring cross metathesis (RCM) was applied to give the 18-membered ring macrolactone. The synthesis of (+)-aspicilin was completed by hydrogenation, selenylation, oxidation, and deprotection.

    中文摘要.............................................I 英文摘要.............................................II 致謝................................................ III 總目錄.............................................. IV 流程圖目錄.......................................... VI 圖目錄...............................................VII 表格目錄.............................................VIII 方程式目錄...........................................IX 附圖目錄.............................................XI 第一章 前言.........................................1 1-1 利用Photolactonization合環，合成天然物(+)-Aspicilin............................................2 1-2 利用Yamaguchi esterification合成天然物(+)-Aspicilin............................................4 1-3 利用allylation與Yamaguchi esterification合成天然物(+)-Aspicilin........................................6 1-4 利用環閉合置換反應(RCM)合成天然物(+)-Aspicilin............................................9 1-5 利用allylation與環閉合置換反應(RCM)合成天然物(+)-Aspicilin............................................12 1-6 利用Wadsworth-Emmons reaction合成天然物(+)-Aspicilin............................................15 1-7 烯烴置換(olefin metathesis)反應的發展史概論....17 1-8 高效能催化劑的問世.............................22 1-9 烯烴置換反應類型...............................25 第二章 結果與討論..................................28 2-1 逆合成分析.....................................28 2-2 起始物合成.....................................30 2-3 (+)-Aspicilin的合成............................31 2-4 路徑A的測試....................................33 2-5 路徑B的測試....................................37 第三章 結論........................................42 第四章 實驗........................................43 4-1 溶媒及處理過程.................................43 4-2 實驗器材與儀器...................................................43 4-3 實驗步驟.......................................45 第五章 參考文獻....................................66

    1. (a) Hesse, O. J. Prakt. Chem. 1900, 62, 430. (b) Hesse, O. J. Prakt. Chem. 1904, 70, 449.
    2. Huneck, S.; Schreiber, K.; Steglich, W. Tetrahedron 1973, 29, 3687.
    3. Quinkert, G.; Heim, N.; Bats, J. W.; Oschkinat, H.; Kessler, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 987.
    4. Quinkert, G.; Heim, N.; Glenneberg, J.; Billhardt, U. M.; Autze, V.; Bats, J. W.; Dürner, G. Angew. Chem., Int. Ed. Engl. 1987, 26, 362.
    5. Kobayashi, Y.; Nakano, M.; Okui, H. Tetrahedron Lett. 1997, 38, 8883.
    6. Marko, I. E.; Dubost, C.; Ryckmans, T. Org. Lett. 2006, 8, 5137.
    7. Banwell, M. G.; McRae, K. J. Org. Lett. 2000, 2, 3583.
    8. Ley, S. V.; Dixon, D. J.; Foster, A. C. Org. Lett. 2000, 2, 123.
    9. Raghavan, S.; Sreekanth, T. Tetrahedron Lett. 2006, 47, 5595.
    10. (a) Rouhi, A. M. CE&E, 2002, 80, 34. (b) Yates, P. J. Am. Chem.Soc. 1952, 74, 5376. (c) Calderon, N.; Chen, H. Y.; Scott, K. W. Tetrahedron Lett. 1967, 8, 3327. (d) Calderon, N. Acc. Chem. Res. 1972, 5, 127. (e) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. (f) Herisson, J.-L.; Chaurin, Y. Makromol. Chem. 1971, 161. (g) Grubbs, R. H.; Carr, D. D.; Hoppin, C.; Burk. P. L. J. Am. Chem. Soc. 1976, 98, 3478. (h) Grubbs, R. H.; Burk. P. L.; Carr, D. D. J. Am. Chem. Soc. 1975, 97, 3265.
    11. Schuster, M.; Blechert, S. Angew. Chem. Int. Ed. Engl. 1997, 36, 2036.
    12. (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem. Int. Ed. Engl. 1995, 34, 2039. (b) Scholl, M.; Ding, S.; Lee, C. W. and Grubbs, R. H. Org. Lett. 1999, 1, 953. (c) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791. (d) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168.
    13. (a) Schuster, M.; Blechert, S. Angew. Chem. Int. Ed. Engl. 1997, 36, 2036. (b) Schmalz, H.-G. Angew. Chem. Int. Ed. Engl. 1995, 34, 1833. (c) Armatrong, S. K. J. Chem. Soc., Perkin Trans. 1, 1998, 371. (d) Grubbs, R. H.; Chang, S. Tetrahedron. 1998, 54, 4413.
    14. (a) Yadav, J. S.; Mysorekar, S. V.; Pawar, S. M.; Gurjar, M. K. J. Carbohydr.Chem. 1990, 9, 307.
    (b) Burke, S. D; Sametz, G. M. Org. Lett. 1999, 1, 71.
    15. Wipf, P.; Soth, M. J. Org. Lett. 2002, 4, 1787.
    16. Coleman, R. S.; Kong, J. S. J. Am. Chem. Soc. 1998, 120, 3538.
    17. (a) Johnson, R. A.; Sharpless, K. B. Comprehensive Organic Synthesis, 1990, Volume 7. Chapter 3.2, asymmetric epoxidations, pergamon Press Oxford.(b) Burns, C. J.; Martin, C. A.; Sharpless, K. B. J. Org. Chem. 1989, 54, 2826.
    18. Makabe, H.; Kimura, Y.; Higuchi, M.; Konno. H.; Murai. M.; Miyoshi. H. Bioorg. Med. Chem. 2006, 14, 3119.
    19. Boyd, D. R.; Sharma, N. D.; Llamas, N. M.; Malone, J. F.; O’Dowd, C. R.; Allen, C. C. R. Org. Biomol. Chem. 2005, 3, 1953.
    20. Tius, M. A.; Fauq, A. H. J. Am. Chem. Soc. 1986, 108, 1035.
    21. (a) Najera, C.; Alonso, D. A.; Varea, M. Tetrahedron Lett. 2001, 42, 8845. (b) Vijayakumar, V.; Ragavan, R. V.; Kumari, N. S. Eur. J. Org. Chem. 2009, 44, 3852.
    22. Donohoe, T. J.; Harris, R. M.; Burrows, J.; Paker, J. J. Am. Chem. Soc. 2006, 128, 13704.
    23. Babin, D.; Demassey, J.; Demoute, J. P.; Dutheil, P.; Terrie, I.; Tessier, J. J. Org. Chem. 1992, 57, 584.
    24. (a) Lansbury, P. T.; Bebernitz, G. E.; Maynard, S. C.; Spagnuolo, C. J. Tetrahedron Lett. 1985, 26, 169. (b) Bunce, R. J.; Dowdy, E. D.; Jones, P. B.; Holt, E. M. J. Org. Chem. 1993, 58, 7143. (c) Omura, S; Hiroyuki, S.; Toshiaki, S; Izuhara, T; Hirose, T; Shiomi, K. Org. Lett. 2007, 9, 65.
    25. Coleman, R. S.; Kong, J. S. J. Am. Chem. Soc. 1998, 120, 3538.
    26. Battiste, M. A.; Strekowski, L.; Visnick, M. J. Org. Chem. 1986, 51, 4836.
    27. Nadin, A.; Sanchez Lopez, J. M.; Neduvelil, J. G.; Thomas, S. R. Tetrahedron 2001, 57, 1861.
    28. Borschberg, H. J.; Hock, S. Helvetica Chimica Acta. 2004, 89, 542.
    29. Karoyan, P.; Quancard, J.; Labonne, A.; Jacquot, Y.; Chassaing, G.; Lavielle, S. J. Org. Chem. 2004, 69, 7940.
    30. Shiina, I.; Kubota, M.; Oshiumi, H.; Hashizume, M. J. Org. Chem. 2004, 69, 1822.
    31. Fustero, S.; Fernandez, B.; Sanz-Cervera, J. F.; Mateu, N.; Mosulen, S.; Carbajo, R. J.; Pineda-Lucena, A.; de Arellano, C. R. J. Org. Chem. 2007, 72, 8716.
    32. Rutjes, F. P. J. T.; Hekking, K. F. W.; Moelands, M. A. H.; van Delft, F. L. J. Org. Chem. 2006, 71, 6444.
    33. Bermejo, F.; Redero, E.; Sandoval, C. Tetrahedron 2001, 57, 9597.

    QR CODE
    :::