中文摘要

本論文內容共分兩個部份：討論藉由36和52的Diels-Alder反應作為關鍵步驟，對clerodane雙萜類天然產物¬¬—(±)-montanin B (47)、 (±)-12-epi-montanin B (48)和 (±)-Teuscoloride (44)進行的合成研究。第二部份則是研究烯丙醇化合物的1,3-氧位移新方法之開發。

第一部份：利用親二烯化合物36和二烯化合物52間的Diels-Alder反應之特殊立體選擇性來建構天然產物骨架中的特定立體化學。Diels-Alder加成產物60經保護後，緊接著進行1,4-加成反應可以得到化合物63。63在鹼性條件下水解可得具有羥基及酮基之中間物51。再利用高壓氫化反應、Jones氧化和酸催化關環(伴隨雙鍵轉移)可得到具備α,β-不飽和內酯環的關鍵中間物67。以Dibal-H對化合物67進行選擇性的還原反應，可得到具有呋喃官能基與一級醇基之中間物46。利用Fétizon試劑與46進行氧化反應可生成具有醛基之化合物47。最後，化合物47經由3-呋喃鋰加成及鹼誘導之關環反應即可完成(±)-montanin A (39)之全合成。透過PDC與DMF的作用，可選擇性將(±)-montanin A (39)中環張力較大的呋喃環氧化成α,β-不飽和-γ-羥基內酯化合物81。以pTSA對81進行酸性脫水反應即完成(±)-Teuscoloride (44)之全合成。

第二部份：首先使烯丙醇化合物1a與mCPBA作用生成環氧化合物2a。在將2a的醇基轉化為甲磺酸酯可得到環氧甲磺酸酯化合物3a。以LN對3a進行還原開環反應可得重排產物¬¬—烯丙醇化合物4a。一系列的研究顯示，以LN針對環氧甲磺酸酯化合物進行還原，能在很短的時間內提供相當不錯的產率，使得所研究之1,3-氧位移新方法非常有效率。

Abstract
The first part of this thesis describes the use of the Diels-Alder cycloaddition reaction between diester 36 and diene 52 for the purpose of achieving the total synthesis of natural products of a high degree of structural complexity. Specifically, the first part details the total synthesis of (±)-teuscoloride (44).
Starting with dienophile 36, Diels-Alder cycloaddition of which with diene 52 furnished tricyclic enone 60. Subsequent 1,4-addition of a methyl group onto the corresponding acetate furnished ketone 63. Base hydrolysis of 63 then allowed for the generation of ketone 51 which was subsequently subjected to a series of reactions including hydrogenation, Jones oxidation, and an acid promoted cyclization and dehydration to give lactone 67. Towards the total synthesis of 44, the intermediate 67 was reduced by Dibal-H in a highly regioselective manner to furnish furan 46. Oxidation of the hydroxyl of furan 46 was achieved by treatment with Fétizon’s reagent to give aldehyde 47, treatment of which with 3-furyllithium followed by base allowed for the completion of the total synthesis of (±)-montanin A (39). (±)-Montanin A (39) was further oxidized with PDC to yield lactone 81 which was subsequently dehydration by treatment with pTSA to complete the total synthesis of (±)-teuscoloride.
The second part of this thesis reports herein a convenient general procedure for the 1,3-allylic alcohol transposition, based on the lithium naphthalenide (LN) induced reductive elimination of epoxy mesylate. The facility of this procedure lies in the ease of preparation of epoxy mesylates from the corresponding allylic alcohol and the subsequent reductive elimination to fulfill the purpose of 1,3-oxygen transposition. For example, epoxidation of the allylic alcohol 1a with m-CPBA in CH2Cl2, followed by treatment of the resulting epoxides 2a with triethylamine and methanesufonyl chloride resulted in the formation of epoxy mesylates 3a. The sequential reductive elimination reaction of 3a was found to occur readily under mild conditions using LN as a reducing reagent to generate the rearrangement product 4a. The results of these and the above mentioned research and studies constitutes the body of this thesis.

參考文獻

第一部份:
1.Merritt, A. T.; Ley, S. V. Nat. Prod. Rep. 1992, 9, 243.
2.Bruno, M.; Bondi, M. L.; Rosselli, S.; Piozzi, F.; Al-Hillo, M. R. Y.; Kaddour, L.; Ladjel, S. J. Nat. Prod. 2000, 63, 1029.
3.Barton, D. H. R.; Cheung, H. T.; Cross, A. D.; Jachman, L. M.; Martin, S. M. J. Chem. Soc. 1961, 5061.
4.(a) Pascual, C. Phytochemistry 1986, 25, 171. (b) Chen, H. M. Chin. Chem. Lett. 1996, 6, 549.
5.李宗和，博士論文，國立清華大學，1996年。
6.Wilson, S. R.; Neubert, L. A.; Hoffman, J. C. J. Am. Chem. Soc. 1976, 98, 3669.
7.Rogers, D.; Unal, G. G.; Williams, D. J.; Ley, S. V. J. Chem. Soc., Chem. Commun. 1979, 97.
8.Fugita E. J. Chem. Soc., Perkin Trans. I 1974, 1547.
9.McCrindle, R.; Nakamura, E.; Anderson, A. B. J. Chem. Soc., Perkin Trans. 1 1976, 1590.
10.Tokoroyama, T.; Fujimori, K.; Shimizu, T.; Yamagiwa, Y.; Monden, M.; Iio, H. J. Chem. Soc., Chem. Commun. 1983, 1516.
11.Tokoroyama, T.; Tsukamoto, M.; Iio, H. Tetrahedron Lett. 1987, 28, 6645.
12.Piers, E.; Breau, M. L.; Han, Y.; Plourde, G. L.; Yeh, W. L. J. Chem. Soc., Perkin Trans. 1 1995, 963.
13.Ly, T. W.; Shia, K. S.; Liu, H. J. “Synthetic Strategies for cis-Clerodane Diterpenoids” in Latest Frontiers of Organic Synthesis, Kobayashi Y., Ed., Research Signpost, 2002, 227.
14.(a) Liu, H. J.; Browne, E. N. Can. J. Chem. 1987, 65, 1262. (b) Liu, H. J.; Ulibarri, G.; Nelson, L. A. K. Can. J. Chem. 1994, 72, 2416. (c) Liu, H. J.; Browne, E. N. C. Can. J. Chem. 1980, 59, 601.
15.Liu, H. J.; Shia, K. S.; Han, Y.; Sun, D.; Wang, Y. Can. J. Chem. 1997, 75, 646.
16.何雲龍，碩士論文，國立清華大學，2000年。
17.(a) Zhu, J. L.; Liu, H. J.; Sha, K. S. Chem. Commun. 2000, 1599. (b) Liu, H. J.; Zhu, J. L.; Sha, K. S. Tetrahedron Lett. 1998, 39, 4183.
18.Förster, H.; Vögtle, F. Angew. Chem. Int. Ed. 1977, 16, 429.
19.Liu, H. J.; Han, Y. Tetrahedron Lett. 1993, 34, 423.
20.(a) Fujita, E.; Uchida, I.; Fujita, T. J. Chem. Soc. Perkin Trans. 1 1973, 793. (b) Fayos, J.; Fernandez-Gagea, F.; Pasanal, C.; Perales, A.; Piozzi, F.; Rico, M.; Rodriguez, B.; Savona, G. J. Org. Chem. 1984, 49, 1789. (c) Malakov, P. Y.; Paponov, G. Y.; Mollov, N. M. Tetrahedron Lett. 1978, 23, 2025. (d) Burno, M.; Bondi, M. L.; Rosselli, S.; Piozzi, F.; Al-Hillo, M. R. Y.; Lamara, K.; Ladjel, S. J. Nat. Prod, 2000, 63, 1029. (e) Fuijta, E.; Uchida, I.; Fuijta, T. Tetrahedron 1975, 31, 841. (f) Labbe, C. L.; Polanco, M. I.; Castillo, M. J. Nat. Prod. 1989, 52, 871. (g) Piozzi, F.; Patemostro, M. P.; Savona, G.; Hanson, J. R.; Hitchcock, P. B.; Sunday, A. T. J. Chem. Soc., Perkin Trans. 1 1979, 1915. (h) Bruno, M.; Piozzi, F.; Savona, G.; Torre, M. C.; Rodriguez, B. Phytochemistry 1989, 28, 3539. (i) Kawahara, M.; Inoue, M.; Kawai, K.; Sekita, S.; Satake, M.; Goda, Y. Phytochemistry, 2003, 63, 859. (j) Savona, G.; Paternostro, M. P.; Piozzi, F.; Hanson, J. R.; Hitchcock, P. B.; Thomas, S. A. J. Chem. Soc., Perkin Trans. 1 1978, 1080. (k) Marco, J. U.; Rodriguez, B.; Savona, G.; Piozzi, F. Phytochemistry 1982, 21, 2567.
21.(a) Liu, H. J.; Zhu, J. L.; Chen, I. C.; Jankowska, R.; Han, Y.; Shia K. S. Angew. Chem. Int. Ed. 2003, 42, 1851. (b) 陳怡佳，博士論文，國立清華大學，2005年。
22.Bergdahl, M.; Linolstedt, E. L.; Nillsson, M.; Olsson, T. Tetrahedron 1989, 45, 535.
23.Han, Y. Ph. D. Thesis, University of Alberta, 1992.
24.Plieninger, H.; Ege, G.; Fisher, R.; Hoffmann, W. Chem. Ber. 1961, 94, 2106.
25.Edwards, J. A.; Orr, J. C.; Bowers, A. J. Org. Chem. 1962, 27, 3378.
26.(a) Mebane, A. D. J. Am. Chem. Soc. 1952, 74, 5227. (b) Tanaka, K.; Ogasawara, K. Synthesis 1995, 1237. (c) Renata, J. Ph. D. Thesis, University of Alberta, 1998.
27.Vassilikogiannakis, G.; Stratakis, M. Angew. Chem. Int. Ed. 2003, 42, 5465.
28.Piancatelli, G.; Scettri, A.; Auria, M. D. Tetrahedron Lett. 1977, 25, 2199.
29.(a) Mckillop, A.; Young, D. W. Synthesis 1979, 6, 401. (b) Kakis, J. P.; Fétizon, M.; Douchkine, N.; Golfier, M.; Mourgues, P.; Prange, T. J. Org. Chem. 1974, 39, 523.
30.Tomioka, H.; Takai, K.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1981, 22, 1605.
31.Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
32.Tidwell, T. T. Synthesis 1990, 10, 857.
33.Savona, G.; Paternostro, M.; Piozzi, F. Tetrahedron Lett. 1979, 20, 379.
34.Marco, J. L.; Rodriguez, B.; Pascual, C.; Savona, G.; Piozzi, F. Phytochemistry 1983, 22, 727.

第二部份:
1.Comprehensive Organic Transformations : A Guide to Functional Group Preparations, Larock, R.H., Ed., Wiley-VCH, 1999, 227.
2.(a) Whitlock, H. W. Jr.; Smith, G. L. J. Am. Chem. Soc. 1967, 89, 3600. (b) Woodward, R. B.; Cava, M. P.; Ollis, W. D.; Hunger, A.; Daenlker, H. U.; Schenker, K. Tetrahedron Lett. 1975, 2045. (c) Woodward, R. B.; Cava, M. P.; Ollis, W. D.; Hunger, A.; Daenlker, H. U.; Schenker, K. J. Am. Chem. Soc. 1954, 76, 4749. (c) Fehr, von T.; Stadler, P. A. Helv. Chim. Acta. 1975, 58, 2484. (d) Babler, J. H.; Olsen, D. O.; Arnold, W. H. J. Org. Chem. 1974, 39, 1656. (e) Babler, J. H. Tetrahedron Lett. 1975, 2045. (f) Letourneux, Y.; Lo, M. M. L.; Chaudhuri, N.; Gut, M. J. Org. Chem. 1975, 40, 516.
3.Marshall, J. A.; Ellison, R. H. J. Am. Chem. Soc. 1976, 98, 4312.
4.(a) Overmna L. E.; Campbell, C. B.; Knoll, F. M. J. Am. Chem. Soc. 1978, 100, 4822. (b) Li, C. J.; Wang, D.; Chen, D. L. J. Am. Chem. Soc. 1995, 117, 12867. (c) Grieco, P.; Takigawa, T.; Bongers, S. L.; Tanaka, H. J. Am. Chem. Soc. 1980, 102, 7587. (d) Henry, P. M. J. Am. Chem. Soc. 1971, 94, 5200. (e) White, J. D.; Johnson, A. J. Org. Chem. 1994, 59, 3347. (f) Cane, D. E.; Yang, G. J. Org. Chem. 1994, 59, 5749.
5.(a) Zoretic, P. A.; Chambers, R. J. J. Org. Chem. 1985, 50, 2981. (b) Johnson, C. R.; Bis, S. J. J. Org. Chem. 1995, 60, 615. (c) Ueno, Y.; Sano, H.; Okawara, M. Synthesis 1980, 1011.
6.Tamao, K.; Kawachi, A.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 3989.
7.Yasuda, A.; Yamamoto, H.; Nozaki, H. Tetrahedron Lett. 1976, 30, 2621.
8.(a) Yasuda, A.; Yamamoto, H.; Nozaki, H. Bull. Chem. Soc. Jan. 1979, 52, 1757. (b) Paquette, L. A.; Ham, H. W. J. Am. Chem. Soc. 1987, 109, 3025.
9.(a) Dittmer, D. C.; Discordia, R. P.; Zhang, Y.; Murphy, C. K.; Kumar, A.; Peptio, A. S.; Wang, Y. J. Org. Chem. 1993, 58, 718. (b) Kumar, A.; Dittmer, D. C. Tetrahedron Lett. 1994, 35, 5583. (c) Diaz, S.; Cuesta, J.; Gonzalez, A.; Bonjoch, J. J. Org. Chem. 2003, 68, 7400.
10.Barton, D. H. R.; Motherwell, R. S. H.; Motherwell, W. B. J. Chem. Soc., Perkin Trans. I 1981, 2363.
11.Lee, E.; Lee, Y. R.; Moon, B.; Kwon, O.; Shim, M. S.; Yun. J. S. J. Org. Chem. 1994, 59, 1444.
12.Zhu, J. L.; Shia, K. S.; Liu, H. J. Chem. Commun. 2000, 1599.
13.Liu, H. J.; Yip, J. Tetrahedron Lett. 1997, 38, 2253.
14.蔡廷岳，博士論文，國立清華大學，2004年。
15.(a) Prilezhaev, N. Ber. 1909, 64, 8041. (b) Rebek, J. Jr.; Marshall, L.; McManis, J.; Wolak, R. J. Org. Chem. 1986, 51, 1649. (c) Kaneti, I. Tetrahedron 1986, 42, 4017.
16.(a) Sharpless, K. B.; Michaelson R. C. J. Am. Chem. Soc. 1973, 95, 6136. (b) Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922.
17.(a) Rossiter, B. E.; Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 464. (b) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Massamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.