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 |
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 |
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).
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.