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研究生： 蘇芳儀
論文名稱： 對掌內酯與對掌內醯胺之不對稱合成
指導教授： 陳焜銘
Chen, Kwun-Min
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2004
畢業學年度： 92
語文別： 中文
論文頁數： 103
中文關鍵詞： 樟腦 、對掌內酯 、對掌三級醇 、對掌內醯胺 、二碘化釤
英文關鍵詞： camphor, chiral lactone, chiral tertiary alcohol, chiral lactam, samarium diiodide
論文種類： 學術論文
相關次數： 點閱：160  下載：13 
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    • 內酯與內醯胺官能基存在天然物及具生物活性的藥物分子中，例如對掌γ-butyrolactones，即常出現於昆蟲用來吸引異性的費洛蒙中，許多具特殊氣味的對掌內酯也常添加於芳香物質中。
    本論文報導了二碘化釤催化對掌α,β-不飽和酯類( 104-109 )與酮( 119, 122-124 )及oxime ether反應生成對掌內酯及對掌內醯胺之反應。以本實驗室開發之樟腦為架構新的對掌輔助劑( 101與103 )，接上α,β-不飽和醯氯後，生成不同取代基之α,β-不飽和酯類。以二碘化釤提供電子和扮演路易士酸的角色，使酮及肟產生碳自由基，與對掌α,β-不飽和酯類進行內酯化及內醯胺化反應，對掌內酯及對掌內醯胺均可得到不錯的鏡像超越值(最高達80% ee)。
    在二碘化釤催化下，對掌α,β-不飽和酯類與苯環取代的酮以二甲基二丙醇為質子源在-78 ℃反應，兩小時後於-78 ℃終止反應，得到內酯化反應之中間產物-對掌三級醇，並得到極高的非鏡像超越值(90% de);若反應回至室溫再將其中止，則可得到對掌內酯並有不錯的鏡像超越值。以本實驗室開發之對掌輔助劑衍生之α,β-不飽和酯類，在二碘化釤提供電子及甲醇為質子源條件下與oxime ether反應，於室溫下可得到鏡像超越值最高為55%的對掌內醯胺129，由n-BuLi及（+）-camphorsulfonyl chloride (130)與對掌內醯胺129反應，產物之絕對立體組態由其X-ray ORTEP鑑定為(R)-構形。

    The lactone and lactam functionality are present in a large variety of natural products and biologically active compounds. For example, certain functionalized chiral γ-butyrolactones are sex attractant pheromones for several insect species and some are utilized as flavoring components. They also constitute a particularly useful class of synthons and chiral building blocks.
    A new chiral auxiliary was prepared to react with acyl chloride, and get α,β-unsaturated carbonyl substrates of exo-10,10-diphenyl-2,10-camphanediol. The formation of lactones was carried out by reaction of various chiral auxiliary derivaties α,β-unsaturated olefins and ketones with samarium diiodide in the presence of t-BuOH at -78 ℃. The reaction was stirred at that temperature for 2hr, and then the reaction was gradually warmed to room temperature. Chiral butyrolactones were obtained in 40-70% yield and 70-80% ee, and chiral auxiliary was recovered at the same time. If the reaction was quenched at -78 ℃, we got reaction intermediates-tertiary alcohols with high diasteroselectivity(>88% de), and de value of the product was determined by crude 1H-NMR.
    If oxime ethers was used instead of keones, the lactamization was proceeded at room temperature and the favored γ-butyrolactam was obtained with 55% ee. The absolute stereochemistry of lactam (129) was determined by single crystal X-ray analysis after reacting with camphorsulfonyl chloride and n-BuLi. The ee value of the product was determined by HPLC using chiral column(AS-H, AD).

    第一章 緒論 1.1 前言 1 1.2對掌內酯與對掌內醯胺在有機合成中之應用 1.2.1 合成生物鹼類天然物 1.2.2 合成大環內酯類抗生素之片段 1.2.3 合成氨基酸及其衍生物 1.2.4 合成醣類化合物 1.3 γ-對掌內酯製備之文獻探討 1.3.1 對掌天然物合成γ-對掌內酯 1.3.2對掌烯丙醇合成對掌內酯 1.3.3 劑量對掌引導(chiral induction)試劑合成對掌內酯 1.3.3.1對掌硫試劑合成γ-對掌內酯 1.3.3.2對掌輔助劑合成γ-對掌內酯 1.3.3.3對掌有機金屬試劑合成γ-對掌內酯 1.3.4 二碘化釤製備γ-對掌內酯 1.3.4.0 前言 1.3.4.1二碘化釤與N-methylephedrine衍生物製備γ-對掌內酯 1.3.4.2二碘化釤與對掌配位基(chiral ligand)製備γ-對掌內酯 1.3.4.3二碘化釤與Isosorbide衍生物製備γ-對掌內酯 1.4 γ-對掌內醯胺製備之文獻探討 1.4.1 天然物製備γ-對掌內醯胺 1.4.2 外消旋β-內醯胺製備γ-對掌內醯胺 1.5 研究動機 第二章 結果與討論 2.1 對掌輔助劑及其衍生物的製備 2.1.1 對掌輔助劑的製備 2.1.2 對掌α,β-不飽和酯類的製備 2.2 γ-對掌內酯化反應 2.2.1 對掌內酯化反應之最佳化條件 2.2.1.1 溫度效應 2.2.1.2 添加物效應 2.2.2取代基效應 2.2.2.1 酮之取代基效應 2.2.2.2 對掌α,β-不飽和酯類之取代基效應 2.2.3 由中間產物-對掌三級醇製備對掌內酯 2.2.3.1 最佳合環條件 2.2.3.2 苯環取代基之效應 2.3 對掌α,β-不飽和酯類之γ-對掌內醯胺化反應 2.3.1對掌α,β-不飽和酯類之取代基效應 2.3.2 肟之取代基效應 2.3.3 絕對立體組態之鑑定 2.3.4 溫度效應 2.3.5對掌輔助劑效應 2.3.6 對掌內醯胺化之可能的反應機構 2.4 結論 第三章 實驗部分 3.1 分析儀器 3.2 實驗部分及光譜數據 3.2.1 立體輔助劑的製備 3.2.2 對掌α,β-不飽和酯類及胺類的製備 3.2.3 對掌內酯的製備 3.2.4 肟(oxime)之製備 3.2.5 對掌內醯胺的製備 第四章 參考文獻

    1. Chamberlin, A. R.; Dezube, M; Reich, S. H.; Sall, D. J. J. Am. Chem. Soc. 1989, 111, 6247.
    2. Koch, C. S. S.; Chamberlin, A. R. J. Org. Chem. 1993, 58, 2725.
    3. (a) Massiot, G.; Delaude, C. in “The Alkaloids”, Bossi, A. Ed. Academic: Orlando, Florida. 1986; Vol. 27, Chapter 3.
    (b) Strunz, G. M.; Findlay, J. A. in “The Alkaloids”, Bossi, A. Ed. Academic: Orlando, Florida. 1985; Vol. 26, Chapter 3.
    4. Yee, N. K. Tetrahedron Lett. 1997, 38, 5091.
    5. Daly, J. W.; Garrafo, H. M.; Spande, T. F. In The Alkaloids; Cordell, G. A., Ed.; San Diego, CA: Academic Press, 1993; p.85.
    6. Santos, L. S.; Pilli, R. A. Tetrahedron Lett. 2001, 42, 6999.
    7. Aoyagi, S.; Hasegawa, Y.;Hirashima, S.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 2149.
    8. Palomo, C.; Aizpurua, J. M.; Cuevas, C.; Urchegui, R.; Linden, A. J. Org. Chem. 1996, 61, 4400.
    9. Durham, T. B.; Miller, M. J. J. Org. Chem. 2003, 68, 27.
    10. Sibi, M. P.; Deshpande, P. K.; Anthony J. Loggia, L.; Christensen, J. W. Tetrahedron Lett. 1995, 36, 8961
    11. (a) Hsieh, K. H.; LaHann, T. R.; Speth, R. C. J. Med. Chem. 1989, 32, 898. (b) Czarniecki, M. F. US Patent 1988. 4, 766,109.
    12. (a) Sibi, M. P.; Jasperse, C. P.; Ji, J. J. Am. Chem. Soc. 1995, 117,10779.
    (b) Sibi, M. P.; Ji, J. Angew. Chem. Int. Ed. Engl. 1996, 36, 190.
    13. (a) Carter, S. K. J. Natl. Cancer Inst. 1975, 55, 1265.
    (b) Skovsgaard, T.; Nissen, N. I. Dan. Ned. Bull. 1975, 22, 62.
    14. (a) Arcamone, F.; Franceschi, G.; Orezzi, P.; Cassinelli, G.; Barbieri, W.; Mondelli, R, J. Am. Chem. Soc. 1964, 86, 5334.
    (b) Arcamone, F.; Franceschi, G.; Orezzi, P.; Cassinelli, G.; Barbieri, W.; Mondelli, R, J. Am. Chem. Soc. 1964, 86, 5335.
    15. Sibi, M. P.; Lu, J.; Edwards, J. J. Org. Chem. 1997, 62, 5864.
    16. (a) Ohloff, G. In Progress in Organic Chemistry; Springer Verlag: Wien, 1987; Vol, 35.
    (b) May, W. A.; Peterson, R. J.; Chang, S. S. J. Food. Sci. 1978, 43, 1248.
    (c) Kingston, B. H. Paifai J. 1983, 5, 11.
    17. Iino, Y.; Tanaka, A.; Yamashita, K. Agric. Biol. Chem. 1972, 36, 2505.
    18. Mori, K. In Techniques in Pheromone Research; Hummel, H.; Miller, T., Eds; Springer Verlag: New York, 1984; Chapter 12.
    19. Tumlinson, J. M.; Klein, M. G.; Dolittle, R. E.; Ladd, T. L.; Proveaux, A. T. Science 1977, 197, 789.
    20. S. Hanessian, “Total synthesis of nature products. The chiron approach”. Pergamon Press, 1983.
    21. Ortuno, R. M.; Alonso, D.; Cardellach, J.; Font, J. Tetrahedron 1987, 43, 2191.
    22. (a) Honda, T.; Ishizone, H.; Mori, W.; Naito, K.; Suzuki, Y. J. Chem. Soc., Perkin Trans. 1, 1991, 3207.
    (b) Honda, T.; Ishige, H.; Tsubuki , M.; Naito, K.; Suzuki, Y. Chem. Pharm. Bull., 1991, 39, 1641
    (c) Honda, T.; Ishige, H.; Tsubuki , M.; Naito, K.; Suzuki, Y. J. Chem. Soc., Perkin Trans. 1, 1991, 954.
    23. Suzuki, Y.; Mori, W.; Naito, K.; Ishige, H.; Honda, T. Tetrahedron Lett. 1992, 34, 4931.
    24. Brown. H. C.; Kulkarni, S. V.; Racherla, U. S. J. Org. Chem. 1994, 59, 365.
    25. Brown. H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.; Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389.
    26. (a) Mioskowski, C.; Solladie, G. J. Chem. Soc., Chem. Commun. 1997, 162.
    (b) Mioskowski, C.; Solladie, G. Tetrahedron 1980, 36, 227.
    (c) Solladie, G. Synthesis 1981, 185.
    27. Solladie, G.; Moghadam, F. M. J. Org. Chem. 1982, 47, 91.
    28. Marino, J. P. and Neisser, M. J. Am. Chem. Soc. 1981, 103, 7687.
    29. Marino, J. P.; Pradilla, R. F. Tetrahedron Lett. 1985, 26, 5381.
    30. Saka, S.; Yamamoto, Y.; Oda, J. J. Am. Chem. Soc. 1987, 109, 7188.
    31. Chong, J. M.; Mar, E. K. Tetrahedron Lett. 1990, 31, 1981.
    32. Paulsen, H.; Hoppe, D. Tetrahedron 1992, 48, 5667.
    33. William, M. J.; Dawson, G. J. Tetrahedron: Asymmetry 1995, 6, 2535.
    34. (a) Kagan, H. B.; Namy, J. L. Tetrahedron 1986, 42, 6573.
    (b) Kagan, H. B. New J. Chem. 1990, 14, 453.
    (c) Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307.
    35. (a) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693.
    (b) Matsukawa, M.; Tabuchi, T.; Inanaga, J.; Yamaguchi, M. Chem. Lett. 1987, 2101.
    (c) Kende, A. S.; Mendoza, J. S. Tetrahedron Lett. 1991, 32, 1699.
    36. Fukuzawa, S.; Nakanishi, A.; Fujinami, T.; Sakai, S. J. Chem. Soc., Chem.
    Commun. 1986, 624.
    37. Fukuzawa, S.; Seki, K.; Tastuzawa, M.; Mutoh, K. J. Am. Chem. Soc. 1997, 119,
    1482.
    38. Mikami, K.; Yamaoka, M. Tetrahedron Lett. 1998, 39, 4501.
    39. Lin, G. Q.; Xu, M. H.; Wang, W. Org. Lett. 2000, 2, 2229.
    40. Silverman, R. B.; Levy, M. A. J. Org. Chem. 1980, 45, 815.
    41. Escalante, J.; Gonzalez-Tototzin, M. A. Tetrahedron: Asymmetry 2003, 14, 981.
    42. (a) Shiue, J.-S.; Lin, C.-C.; Fang, J.-M. Tetrahedron Lett. 1993, 34, 335.
    (b) Shiue, J.-S.; Lin, M.-H.; Fang, J.-M. J. Org. Chem. 1997, 62, 4643.
    43. Ishii, Y.; Akane, N.; Hantano, T.; Kusui, H.; Nishiyama, Y. J. Org. Chem. 1994, 59, 7902.
    44. Kagan, H. B.; Souppe, J.; Danon, L.; Namy, J. L. J. Organomet. Chem. 1983,
    250, 227.

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