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研究生： 盧可禎
Ke-Jhen Lu
論文名稱： 首次合成Cladospolide D和確認其立體化學
First Synthesis and Structure Determination of Cladospolide D
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： 96
語文別： 中文
論文頁數： 239
中文關鍵詞： 交叉置換 、酯化反應 、保護基 、D-甘露醣醇 、硫醇 、水解 、去保護 、環合置換 、天然物
外文關鍵詞： Cross Metathesis, Dess-Martin periodinane, Yamaguchi, ring-closing metathesis, Hoveyda-Grubbs Catalyst, Grubbs’cat., Michael addition, Cladospolide D
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    • 利用掌性的雙烯雙醇35與(RS)乙酸庚-6-烯-2-酯63為起始物合成 (5R,11R)-Cladospolide D (1a) 和 (5R,11S)-Cladospolide D (1b)。保護後之35先與丙烯酸甲酯進行第一次的交叉置換反應，然後在羥基上作保護基的轉換再與烯63進行第二次的交叉置換反應來導入C11的掌性中心。然後利用正丁硫醇進行Michael addition，接著氫化雙鍵，再以m-CPBA和DBU重新生成共軛雙鍵。酯基水解後之酸進行Yamaguchi內酯化反應得到十二員環的內酯。選擇性去除保護後氧化得到酮，最後再去除保護基得到1a和1b。鑑定天然物Cladospolide D結構為1b，即 (6R,12S,E)-6-hydroxy-12-methyloxacyclododec-3-ene-
    2,5-dione。

    (5R,11R)-Cladospolide D (1a) and (5R,11S)-Cladospolide D (1b) was synthesized using diene 35 and (RS)-hept-6-en-2-yl acetate 63 as the strating materials. The first cross metatheses (CM) reaction of protected 35 with methyl acrylate and the following deprotection provided the ester 57. Then the second cross metatheses reaction of ester 57 and alkene 63, Michael addition with n-butanethiol, hydrogenation, oxidation and elimination by m-CPBA and DBU, regenerated the α,β-unsaturated ester. After hydrolysis of the ester group and the Yamaguchi lactonization, the twelve-membered lactone was obtained. Selective deprotections and oxidation provided the target 1a and 1b. Therefore, the structure of Cladospolide D is established as (6R,12S,E)-6-hydroxy-12-
    methyloxacyclododec-3-ene-2,5-dione (1b)。

    中文摘要…………………………………………………………………i Abstract………………………………………………………………ii 誌謝……………………………………………………………………iii 目錄……………………………………………………………………iv 圖目錄……………………………………………………………… vi 表目錄……………………………………………………………… vii 流程圖目錄………………………………………………………… viii 反應式目錄………………………………………………… ix 光譜資料目錄……………………………………………………… xii 第一章 前言………………………………………………………… 1 1-1 經由RCM來合成(+)-Aspicilin…………………………… 3 1-2 利用交叉置換(Cross Metathesis)-內酯化(Lactonization) 反應來合成大環內酯的抗生素(-)-A26771B………………6 1-3 合成(+)-Cladospolide C…………………………………… 8 1-4 烯烴置換(olefin metathesis)反應的發展史概論……… 10 1-5 高效能催化劑的問世…………………………………………14 1-6 烯烴置換反應類型……………………………………………17 1-7 交叉置換(Cross Metathesis)反應介紹………………… 20 1-8 研究動機………………………………………………………23 第二章 結果與討論…………………………………………… 24 2-1 逆合成分析………………………………………………… 24 2-2 起始物的合成……………………………………………… 28 2-3 路徑A的測試……………………………………………… 31 2-4 路徑B的測試…………………………………………………34 2-5 路徑C的測試…………………………………………………42 2-6 天然物Cladospolide D的合成…………………………… 46 第三章 結論………………………………………………………… 52 第四章 實驗……………………………………………………………53 4-1溶媒及處理過程………………………………………………53 4-2 實驗器材與儀器………………………………………………53 4-3 實驗步驟………………………………………………………55 第五章 參考文獻…………………………………………………… 112

    1. Zhang, H.；Tomoda, H.；Tabata, N.；Miura, H.；Namikoshi, M.；Yamaguchi, Y.；Masuma, R.；Omura, S. J. Antibiot. 2001, 54, 635-641.
    2. Pandey, S. K.；Kumar, P. Tetrahedron Lett. 2005, 46, 6625-6627.
    3. Hirota, A.；Isogai, A.；Sakai, H. Agric. Biol. Chem. 1981, 45, 799-800.
    4. (a) Hirota, A.；Sakai, H.；Isogai, A. Agric. Biol. Chem. 1985, 49, 731-735；(b) Hirota, H.；Hirota, A.；Sakai, H.；Isogai, A.；Takahashi, T. Bull. Chem. Soc. Jpn. 1985, 58, 2147-2148.
    5. (a) Smith, C. J；Abbanat, D.；Bernan, V. S.；Maiese, W. M.；Greenstein, M.；Jompa, J.；Tahir , A.；Ireland, C. M. J. Nat. Prod. 2000, 63, 142-145；(b) Franck, X.；Araujo, M. E. V.；Jullian, J.-C.；Hocquemiller, R.；Figadere, B. Tetrahedron Lett. 2001, 42, 2801-2803.
    6. Fujii, Y.；Fukuda, A.；Hamasaki, T.；Ichimoto, I.；Nakajima, H. Phtochemistry 1995, 40, 1443-1446.
    7. (a) Banwell, M. G.；Loong, D. T. J.；Willis, A. C. Aust. J. Chem. 2005, 58, 511-516；(b) Austin A. B. K.；Banwell, M. G.；Loong, D. T. J.；Rae, A. D.；Willis, A. C. Org. Biomol. Chem. 2005, 3, 1081-1088；(c) Banwell, M. G.；Loong, D. T. J. Org. Biomol. Chem. 2004, 2, 2050-2060；(d) Banwell, M. G.；Jolliffe, K. A.；Loong, D. T. J.；McRae, K. J.；Vounatsos, F. J. Chem. Soc., Perkin Trans. 1, 2002, 22-25.
    8. Banwell, M. G.；McRae, K. J. Org. Lett. 2000, 2, 3583-3586.
    9. Gebauer, J；Blechert, S. J. Org. Chem. 2006, 71, 2021-2025.
    10. Chou, C-Y.；Hou, D-R. J. Org. Chem. 2006, 71, 9887-9890.
    11. (a) Rouhi, A. M. CE&E, 2002, 80, 34-38；(b)Yates, P. J. Am. Chem. Soc. 1952, 74, 5376-5381；(c) Calderon, N.；Chen, H. Y.；Scott, K. W. Tetrahedron Lett. 1967, 8, 3327-3329；(d) Calderon, N. Acc. Chem. Res. 1972, 5, 127-132；(e) Trnka, T. M.；Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29；(f) Hérisson, J.-L.；Chaurin, Y. Makromol. Chem. 1971, 161-167；(g) Grubbs, R. H.；Carr, D. D.；Hoppin, C.；Burk. P. L. J. Am. Chem. Soc. 1976, 98, 3478-3483；(h) Grubbs, R. H.；Burk. P. L.；Carr, D. D. J. Am. Chem. Soc. 1975, 97, 3265-3267.
    12. (a) Tsuji, J.；Hashiguchi, S. Tetrahedron Lett. 1980, 21, 2955-2958；(b) Schwab, P.；France, M. B.；Ziller, J. W.；Grubbs, R. H. Angew. Chem. Int. Ed. Engl. 1995, 34, 2039-2041；(c) Scholl, M.；Ding, S.；Lee, C. W. and Grubbs, R. H. Org. Lett. 1999, 1, 953-956.；(d) Kingsbury, J. S.；Harrity, J. P. A.；Bonitatebus, P. J.；Hoveyda,
    A. H. J. Am. Chem. Soc. 1999, 121, 791-799；(e) Garber, S. B.；Kingsbury, J. S.；Gray, B. L.；Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-8179.
    13. (a) Schuster, M.；Blechert, S. Angew. Chem. Int. Ed. Engl. 1997, 36, 2036-2056；(b) Schmalz, H.-G. Angew. Chem. Int. Ed. Engl. 1995, 34, 1833-1836；(c) Armatrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371-388；(d) Grubbs, R. H.；Chang, S. Tetrahedron. 1998, 54, 4413-4450.
    14. Chatterjee, A. K.；Choi, T. L.；Sanders, D. P.Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360-11270.
    15. (a) Brummer, O.；Ruckert, A；Blechert, S. Chem-Eur. J. 1997, 3, 441-444；(b) Crowe, W. E.；Zhang, Z. J. J. Am. Chem. Soc. 1993, 115, 10998-10999.
    16. Burke, S. D；Sametz, G. M. Org. Lett. 1999, 1, 71-74.
    17. Chai, K. B.；Paul, S. J. Org. Chem. 1993, 58, 6807-6813.
    18. Dixon, D. J.；Ley, S. V.；Tate, E. W. J. Chem. Soc., Perkin Trans. 1, 2000, 2385-2394.
    19. Vilaca, G.；Rubio, C.；Susperregui, J.；Latxague, L.；De´le´ris,G. Tetrahedron 2002, 58, 9249-9256.
    20. Quinn, K. J.；Isaacs, A. K.；DeChristopher, B. A.；Szklarz, S. C.；Arvary, R. A. Org. Lett. 2005, 7, 1243-1245.
    21. Wipf, P.；Soth, M. J. Org. Lett. 2002, 4, 1787-1790.
    22. Posner, G. H.；Haces, A.；Harrison, W.；Kinter, C. M. J. Org. Chem. 1987, 52, 4836-4841.
    23. Forman, G. S.；McConnell, A. E.；Tooze, R. P.；Rensburg, W. J. V.；Meyer, W. H.；Kirk, M. M.；Dwyer, C. L.；Serfontein, D. W. Organometallics 2005, 24, 4528-4542.
    24. Sheddan, N. A.；Arion, V. B.；Mulzer, J. Tetrahedron Lett. 2006, 47, 6689-6693.
    25. Sheddan, N. A.；Mulzer, J. Org. Lett. 2006, 8, 3101-3104.
    26. Boruwa, J.；Gogoi, N.；Barua, N. C. Org. Biomol. Chem. 2006, 4, 3521-3525.
    27. Shiina, I.；Kubota, M.；Oshiumi, H.；Hashizume, M. J. Org. Chem. 2004, 69, 1822-1830.
    28. Andrus, M. B.；Meredith, E. L.；Sekhar, B. B. V. S. Org. Lett. 2001, 3, 259-262.
    29. Inanaga, J.；Hirata, K.；Saeki, H.；Katsuki, T.；Yamaguchi, M. Bull. Chem. Soc. Jpn. 1979, 53, 1989-1993.
    30. Sakaguchi, H.；Tokuyama, H.；Fukuyama, T. Org. Lett. 2007, 9, 1635-1638.
    31. (a) Kawaguchi, T.；Funamori, N.；Matsuya, Y.；Nemoto, H. J. Org. Chem. 2004, 69, 505-509；(b) Fu1rstner, A.；Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130-9136.
    32. (a) Vincent, G.；Mansfield, D.J.；Vors, J.-P.；Ciufolini, M. A. Org. Lett. 2006, 8, 2791-2794；(b) Kanada, R.M.；Itoh, D.；Nagai, M.；Niijima, J.；Asai, N.；Mizui, Y.；Abe, S.；Kotake, Y. Angew. Chem. Int. Ed. 2007, 46, 4350-4355.
    33. (a) Ramachandran, P. V.；Liu, H.；Reddy, M. V. R.；Brown, H. C. Org. Lett. 2003, 5, 3755-3757；(b) Kim, S.；Part, Y. H.；Kee, I. S. Tetrahedron Lett. 1991, 32, 3099-3100；(c) Paek, S. -M.；Seo, S.-Y.；Kim, S.-H.；Jung, J.-W.；Lee, Y.-S.；Jung, J.-K.；Suh, Y.-G. Org. Lett. 2005, 7, 3159-3162.
    34. (a) Lombaert, S. D.；Lesur, B.；Ghosez, L. Tetrahedron Lett. 1982, 23, 4251-4254；(b) Tam, W.；Riddell, N. J. Org. Chem. 2006, 71, 1934-1937；(c) Lombaert, S. E.；Ghosez, L. Tetrahedron Lett. 1984, 25, 3475-3478.
    35. (a) Bauer, J.；Brandenburg, K.；Zahringer, U.；Rademann, J. Chem. Eur. J. 2006, 12, 7116-7124；(b) Boeckman, R. K.；Potenza, J. C. Tetrahedron Lett. 1985, 26, 1411-1414.
    36. Ingerl, A.；Justus, K.；Hellwig, V.；Steglich, W. Tetrahedron 2007, 63, 6548-6557.
    37. Matsuya, .Y；Kawaguchi, T.；Ishihara, K.；Ahmed, K.；Zhao, Q.-L.；Kondo, T.；Nemoto, H. Org. Lett. 2006, 8, 4609-4612.
    38. Fujioka, H.；Ohba, Y.；Nakahara, K.；Takatsuji, M.；Murai, K.；Ito, M.；Kita, Y. Org. Lett. 2007, 9, 5605-5608.

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