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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:179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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