石松生物碱（-）-8-Deoxyserratinine的全合成
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摘要
石松生物碱(Lycopodium alkaloids)是从蕨类植物石松及其近缘植物(Lycopodium related plants)中分离得到的结构相似,具有相同生源途径的一类天然生物碱。广泛存在于石松及其类似植物种群,特别是石杉科(Huperziaceae)和石松科(Lycopodiaceae)植物。此类生物碱通常都具有极其独特的骨架和良好的生物活性,因此引起了药学家和有机化学家的广泛关注。1986年,中国科学家刘嘉森从传统中医千层塔分离了石杉碱甲(Huperzine A)并发现其是一种高效的乙酰胆酯酶抑制剂,此后成为药学界备受瞩目的研究热点之一,推动了石松生物碱的研究,包括全合成研究。作为极具挑战的全合成多环分子,有机合成化学家对其表现出浓厚的兴趣,近年来已完成了一些石松生物碱的全合成工作。本论文主要研究了对Fawcettimine型石松生物碱合成方法研究,最终通过高效、简洁的途径成功完成了(-)-8-deoxyserratinine的首次不对称合成。
本论文共分三章,第一章主要介绍了石松生物碱在天然产物化学、药物化学和有机合成化学中的重要地位及研究进展。重点介绍了Fawcettimine型石松生物碱的合成研究进展,对fawcettimine、sieboldine A、Paniculate、Magellanine和Magellaninone等分子的合成研究进行综述。
第二章首先介绍Inubushi小组对Serratinine和8-Deoxyserratinine的合成工作,然后开始介绍我们对(-)-8-D eoxyserratinine的不对称全合成研究工作。从(+)-pulegone 202大量制备的烯酮化合物(-)-187作为起始原料,通过15步反应以7%的总收率,高效地完成了(-)-8-Deoxyserratinine的不对称全合成。我们的核心策略包括三个方面：1.通过高效的Helquist环化方法来构建顺式6/5双环；2.通过氮双烷基化策略简洁地构筑氮杂9元环；3.运用不对称Shi氧化立体专一性地制备β-环氧化合物。
第三章为论文中相关化合物的合成实验操作及其谱图数据。
Lycopodium alkaloids are isolated from the pteridophyta lycopodium and related plants with similar biogenesis. These compounds present in lycopodium and related species, especially plants of Huperziaceae and Lycopodiaceae. The Lycopodium alkaloids often possess unusual skeletons and promising bioactivity, which attract the attention of numerous organic chemists and medicinal chemists. In 1986, Jiasen-Liu, a Chinese scientist, isolated Huperzine A from Huperzia serrata, a traditional Chinese medicine. Huperzine A has been shown to be a potent, reversible inhibitor of acetylcholine esterase and significantly impacts the investigate of Lycopodium alkaloids. Owing to their appealing biological activities as well as synthetically challenging polycyclic systems, a number of total syntheses of Lycopodium alkaloids have been conducted and documented in the literature.
This thesis describes the synthetic studies on Lycopodium alkaloids of fawcettimine class, the first asymmetric total synthesis of (-)-8-Deoxyserratinine was successfully realized and summarized in this thesis.
Three chapters are included in this thesis. In the first chapter, we summarized the synthesis of fawcettimine class alkaloids, including fawcettimine、sieboldine A、paniculate、Magellanine and magellaninone.
In chapter 2, studies towards the first asymmetric total synthesis of (-)-8-Deoxyserratinine was described. We completed the first enantioselective total synthesis of (-)-8-Deoxyserratinine in 15 steps from enone (-)-187 with 7% overall yield. The key features include a highly efficient Helquist annulation to furnish the cis-fused 6/5 bicycle, construction of the aza nine-membered ring system employing double N-alkylation strategy and asymmetric Shi epoxidation to secure the desiredβ-epoxide stereospecifically.
Experiment procedure, physical and spectrum data for compounds described in Chapter 2 are recorded in Chapter 3.
本论文共分三章,第一章主要介绍了石松生物碱在天然产物化学、药物化学和有机合成化学中的重要地位及研究进展。重点介绍了Fawcettimine型石松生物碱的合成研究进展,对fawcettimine、sieboldine A、Paniculate、Magellanine和Magellaninone等分子的合成研究进行综述。
第二章首先介绍Inubushi小组对Serratinine和8-Deoxyserratinine的合成工作,然后开始介绍我们对(-)-8-D eoxyserratinine的不对称全合成研究工作。从(+)-pulegone 202大量制备的烯酮化合物(-)-187作为起始原料,通过15步反应以7%的总收率,高效地完成了(-)-8-Deoxyserratinine的不对称全合成。我们的核心策略包括三个方面：1.通过高效的Helquist环化方法来构建顺式6/5双环；2.通过氮双烷基化策略简洁地构筑氮杂9元环；3.运用不对称Shi氧化立体专一性地制备β-环氧化合物。
第三章为论文中相关化合物的合成实验操作及其谱图数据。
Lycopodium alkaloids are isolated from the pteridophyta lycopodium and related plants with similar biogenesis. These compounds present in lycopodium and related species, especially plants of Huperziaceae and Lycopodiaceae. The Lycopodium alkaloids often possess unusual skeletons and promising bioactivity, which attract the attention of numerous organic chemists and medicinal chemists. In 1986, Jiasen-Liu, a Chinese scientist, isolated Huperzine A from Huperzia serrata, a traditional Chinese medicine. Huperzine A has been shown to be a potent, reversible inhibitor of acetylcholine esterase and significantly impacts the investigate of Lycopodium alkaloids. Owing to their appealing biological activities as well as synthetically challenging polycyclic systems, a number of total syntheses of Lycopodium alkaloids have been conducted and documented in the literature.
This thesis describes the synthetic studies on Lycopodium alkaloids of fawcettimine class, the first asymmetric total synthesis of (-)-8-Deoxyserratinine was successfully realized and summarized in this thesis.
Three chapters are included in this thesis. In the first chapter, we summarized the synthesis of fawcettimine class alkaloids, including fawcettimine、sieboldine A、paniculate、Magellanine and magellaninone.
In chapter 2, studies towards the first asymmetric total synthesis of (-)-8-Deoxyserratinine was described. We completed the first enantioselective total synthesis of (-)-8-Deoxyserratinine in 15 steps from enone (-)-187 with 7% overall yield. The key features include a highly efficient Helquist annulation to furnish the cis-fused 6/5 bicycle, construction of the aza nine-membered ring system employing double N-alkylation strategy and asymmetric Shi epoxidation to secure the desiredβ-epoxide stereospecifically.
Experiment procedure, physical and spectrum data for compounds described in Chapter 2 are recorded in Chapter 3.
引文
1. Ayer, W.A. The Lycopodium alkaloids. [J]. Nat. Prod. Rep,1991,8,455-463.
2. a). Manske, R.H.F. The Alkaloids.; Academic Press:New York,1955,5,295-300. b). Maclean, D.B. The Alkaloids.; Academic Press:New York,1968,10,305-382. c). Ayer W.A. Trifonow, L.S. The Alkaloids.; Academic Press:New York,1994,45,233.
3.刘嘉森,俞超美,周有作,韩燕艺,吴凤梧,戚宝凤,朱元龙.石杉碱甲和石杉碱乙的化!学研究.[J].化学学报,1986,44,1035-1040.
4. Burnell, R. H. Lycopodium alkaloids. I. Extraction of alkaloids from Lycopodium fawcettii. [J] J. Chem. Soc,1959,3091-3093
5. a). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. Serratinine:A novel skeletal lycopodium alkaloid. [J]. Chem. Pharm. Bull,1968,16,82-91. b). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. The Plane Structure of Serratinine. [J]. Chem. Pharm. Bull, 1968,16,92-100. c). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. The Plane Structure of Serratinine. [J]. Chem. Pharm. Bull,1968,16,101-112
6. Inubushi, Y.; Ishii, H.; Yasui, B.; Harayama, T.; Hosokawa, M.; Nishino, R.; Nakahara Y Constituents of domestic Lycopodium plants. Ⅶ. Alkaloid constituents of L. serratum var serratum f. serratumand L. serrarum var serratum f. intermedium. [J]. Yakugaku. Zasshi,1967, 87,1394-1404.
7. Ayer, W.A.; Altenkirk, B.; Fukazawa, Y. Alkaloids of Lycopodium alopecuroides L.-V:The structure of Alopecuridine. [J]. Tetrahedron,1974,30,4213-4214.
8. a). Castillo, M.; Morales, G.; Loyola, L. A.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. Paniculatine. A New Alkaloid from L. paniculatum Desvaux. [J]. Can. J. Chem,1975,53, 2513-2514. b). Castillo, M.; Morales, G.; Loyola, L.A.; Singh, I.; Calvo C.; Holland, H.L. MacLean, D. B. Paniculatine. The alkaloids of L. paniculatum and the structure of paniculatine. [J]. Can. J. Chem,1975,54,2900-2908.
9. Ayer, W.A.; Fukazawa, Y.; Singer, P. P. Lycoflexine, a new type of lycopodium alkaloid. [J]. Tetrahedron Lett,1973,14,5045-5048.
10. a) Ma, X.; Gang, D. R. The Lycopodium alkaloids. [J]. Nat. Prod. Rep.2004,21,752-772. b) Hirasawa, Y.; Kobayashi, J.; Morita, H. The Lycopodium alkaloids. [J]. Heterocycles,2009,77, 679-729.
11.Gao,W.Y.; Wang, B.D.; Li,Y.M.; Jiang, S.H.; Zhu, D.Y. Anew alkaloid and arbutin from the whole plant of Huperzia serrata. [J]. Chin. J. Chem,2000,18,614-616.
12.袁珊琴,赵毅民,冯锐.蛇足石杉新碱的结构鉴定.[J].药学学报2002,37,946-949
13. Tan, C.H.; Ma, X.Q.; Chen, G.F.; Zhu, D.Y. Huperzines S, T, and U:New Lycopodium alkaloids from Huperzia serrata. [J]. Can. J. Chem,2003,81,315-318.
14. Takayama, H. Katakawa, K. Kitajima, M. Yamaguchi, K. Aimi, N. Seven new Lycopodium alkaloids, lycoposerramines-C,-D,-E,-P,-Q,-S, and-U, from Lycopodium serratum Thunb. [J]. Tetrahedron Lett,2002,43,8307-8311.
15. Takayama, H.; Katakawa, K.; Kitajima, M.; Seki, H.; Yamaguchi, K.; Aimi, N. A New Type of Lycopodium Alkaloid, Lycoposerramine-A, from Lycopodium serratum Thunb. [J]. Org. Lett, 2001,3,4165-4167.
16. Katakawa, K.; Kitajima, M.; Aimi, N.; Seki, H.; Yamaguchi, K.; Furihata, K.; Harayama, T.; Takayama, H. Structure Elucidation and Synthesis of Lycoposerramine-B, a Novel Oxime-Containing Lycopodium Alkaloid from Lycopodium serratum Thunb. [J]. J. Org. Chem, 2005,70,658-663.
17. Katakawa, K.; Kogure, N.; Kitajima, M.; Takayama, H. A new Lycopodium alkaloid, Lycoposerramine-R, with a novel skeleton and three new faweettimine-related alkaloids from serratum. [J]. Helv. Chim. Aeta,2009,92,445-452.
18. Hirasawa, Y.; Morita, H.; Shiro, M.; Kobayashi, J. Sieboldine A, a Novel Tetracyclic Alkaloid from Lycopodium sieboldine, Inhibiting Acetylcholinesterase. [J]. Org. Lett,2003,5,3991.
19. Koyama, K.; Morita, H.; Hirasawa, Y.; Yoshinaga, M.; Hoshino, T.; Obara, Y.; Norimichi N.; Kobayashi, J. Lannotinidines A-G, new alkaloids from two species of Lycomdium. [J]. Tetrahedron,2005,61,3681-3690.
20. Kubota, T.; Sunaura, T.; Morita, H.; Mikami,Y;Hoshino,T.;Obara,Y.;Nakahata,N.;Kobayashi,J. Lycovatine A, a C16 N-type quaternary alkaloid from Lycopodium Clavatum var.Robustum. [J]. Heterocycles,2006,69,469-474.
21. He, J.; Chen, X.Q.; Li, M.M.; Zhao, Y.; Xu, G.; Cheng, X.; Peng, L.Y.; Xie, M.J.; Zheng, Y.T.; Wang, Y.P.; Zhao, Q.S. Lycojapodine A, a novel alkaloid from Lycopodium japonicum. [J]. Org. Lett,2009,11,1397-1400.
22. Zhao, F.W.; Sun, Q.Y.; Yang, F.M.; Hu, G.W.; Luo, J.F.; Tang, G.H.; Wang, Y.H.; Long, C.L. Palhinine A, a Novel Alkaloid from Palhinhaea cernua. [J]. Org. Lett,2010,12,3922-3925.
23.陈业高,刘怡君,蒋金和,刘波.石松类生物碱成分研究的新进展.[J].云南师范大学学学报,2010,30,12-24.
24.谭昌恒,朱大元.石松生物碱研究进展.[J].中国天然药物,2003,1,1-7.
25. Ayer, W.A.; Ma, Y.T.; Liu, J.S.; Huang, M.F.; Schultz, L.W.; Clardy, J. Macleanine, a unique type of dinitrogenous Lycopodiurn alkaloid. [J]. Can. J. Chem,1994,72,128-130.
26. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Am. Chem. Soc,1986,108,5022-5024.
27. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Org. Chem,1989,54,1548-1562.
28. Linghu, X.; Kennedy-Smith, J. J.; Toste, F. D. Total Synthesis of (+)-Fawcettimine. [J]. Angew. Chem. Int. Ed,2007,46,7671-7673.
29. Staben, S. T.; Kennedy-Smith, J. J.; Huang, D.; Corkey, B. K.; LaLonde, R. L.; Toste, F. D. Gold(I)-Catalyzed Cyclizations of Silyl Enol Ethers:Application to the Synthesis of (+)-Lycopladine A. [J]. Angew. Chem. Int. Ed,2006,45,5991-5994.
30. Kozaka, T.; Miyakoshi, N.; Mukai, C. Stereoselective Total Syntheses of Three Lycopodium Alkaloids, (-)-Magellanine, (+)-Magellaninone, and (+)-Paniculatine, Based on Two Pauson Khand Reactions. [J]. J. Org. Chem,2007,72,10147-10154.
31.Otsuka,Y.;Inagaki, F.; Mukai, C. Total Syntheses of (+)-Fawcettimine and (+)-Lycoposerramine B. [J].J. Org. Chem,2010,75,3430-3426.
32. Fang, J.; Ren, J.; Wang, Z. Sc(OTf)3-catalyzed smooth tandem [3+2] cycloaddition/ring opening of donor-acceptor cyclopropane 1,1-diesters with enol silyl ethers. [J]. Tetrahedron Lett, 2008,49,6659-6662.
33. Qu, J.-P.; Deng, C.; Zhou, J.; Sun, X.-L.; Tang, Y. Switchable Reactions of Cyclopropanes with Enol Silyl Ethers. Controllable Synthesis of Cyclopentanes and 1,6-Dicarbonyl Compounds. [J]. J. Org. Chem,2009,74,7684-7689.
34. Jung, M.E.; Chang, J.J. Enantiospecific Formal Total Synthesis of (+)-Fawcettimine. [J]. Org. Lett,2010,12,2962-2965.
35. Castillo, M.; Loyola, L. A.; Morales, G.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. The alkaloids of L. magellanicum and the structure of magellanine. [J]. Can. J. Chem,1976,54, 2893-2899.
36.Loyola, L.A.; Morales,G.; Castillo,M. Alkaloids of Lycopodium magellanicum. [J]. Phytochemistry,1979,18,1721-1723.
37. Hirst, G.C.; Johnson, T. O.; Jr.; Overman, L. E. First Total Synthesis of Lycopodium Alkaloids of the Magellanane Group. Enantioselective Total Syntheses of (-)-Magellanine and (+)-Magellaninone. [J].J. Am. Chem. Soc,1993,115,2992-2993.
38. Overman, L.E. Change as a key component in reaction design. The invention of cationic reactions of importance in synthesis. [J].Acc. Chem.Res,1992,25,352-359.
39. Overman, L.E. New reactions for forming heterocycles and their use in natural products synthesis. [J]. Aldrichmica Acta,1995,28,107-120.
40. Ando, S.; Minor, K.P.; Overman, L.E.; Ring-Enlarging Cyclohexane Annulations. [J]. J. Org. Chem,1997,62,6379-6387.
41. Paquette, L. A.; Friedrich, D.; Pinard, E.; Williams, J. P.; Laurent, D. St.; Roden, B. A. Total Synthesis of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone. [J]. J. Am. Chem. Soc,1993,115,4377-4378.
42. Williams, J. P.; Laurent, D.R.St.; Friedrich, D.; Pinard, E.; Roden, B. A.;Paquette, L. A. Total Synthesis of the Lycopodium Alkaloids Magellanine and Magellaninone by Three-fold Annulation of 2-Cyclopentenone. [J]. J. Am. Chem. Soc,1994,116,4689-4696.
43. Yen, C.F.; Liao, C.C.; Concise and Efficient Total Synthesis of Lycopodium Alkaloid Magellanine. [J]. Angew. Chem. Int. Ed,2002,41,4090-4093.
44. Hsu, D-S.; Rao, P.D.; Liao, C.C. Short and efficient route to substituted linear triquinanes from 2-methoxyphenols. [J]. Chem. Commun,1998,17,1795-1796.
45.Tsunoda, T.; Suzuki, M.; Noyori, R. A facile procedure for acetalization under aprotic conditions. [J]. Tetrahedron Lett,1980,21,1357-1358.
46.1reland, R.E.; Mueller, R.H.; Willard,A.K. The ester enolate Claisen rearrangement. Stereochemical control through stereoselective enolate formation. [J]. J. Am. Chem. Soc,1976, 98,2868-2877.
47. Chai, Y.; Hong, S-P.; Lindsay, H.A.; McFarland, C.; McIntosh, M.C. New aspects of the Ireland and related Claisen rearrangements. [J]. Tetrahedron,2000,58,2905-2928.
48. Khand, I.U.; Knox, G.R.; Pauson, P.L.; Watts, W.E.; Foreman, M.I. Organocobalt complexes. II.Reaction of acetylenehexacarbonyl dicobalt complexes, (RC2R1)Co2(CO)6, with norbornene and its derivatives. [J]. J. Chem. Soc, Perkin Trans,1973,977-981.
49.Schore, N.E.; Croudace, M.C. Preparation of bicyclo[3.3.0]oct-l-en-3-one and bicyclo[4.3.0]non-1(9)-en-8-one via intramolecular cyclization of α,ω-Enynes. [J]. J. Org. Chem,1981,46,5436-5438.
50. Ishizaki, M.; Niimi Y.; Hoshino, O. Formal total synthesis of (±)-magellanine. [J]. Tetrahedron Lett,2003,44,6029-6031.
51. Ishizaki, M.; Niimi, Y.; Hoshino, O.; Harab, H.; Takahashi, T. A formal total synthesis of Lycopodium alkaloid,(±)-magellanine, by using the intramolecular Pauson Khand reaction. [J]. Tetrahedron,2005,61,4053-4065.
52. Ryu, I.; Sonoda, N.; Curran, D. P. Tandem Radical Reactions of Carbon Monoxide, Isonitriles, and Other Reagent Equivalents of the Geminal Radical Acceptor/Radical Precursor Synthon. [J].Chem. Rev,1996,96,177-194.
53. Parsons, P. J.; Penkett, C. S.;Shell, A. J. Tandem Reactions in Organic Synthesis:Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. [J].Chem. Rev,1996,96,195-206.
54. Sha, C.-K.; Jean, T.-S.; Wang, D.-C. Intramolecular radical cyclization of silylacetylenic or olefinic a-iodo ketones:Application to the total synthesis of (±)-modhephene. [J]. Tetrahedron Lett,1990,31,3745-3748.
55. Sha, C.-K.; Chiu, R.-T.; Yang, C.-F.; Yao, N.-T.; Tseng, W.-H.; Liao, F.-L.; Wang, S.-L. Total Synthesis of (-)-Dendrobine via a-Carbonyl Radical Cyclization. [J]. J. Am. Chem. Soc,1997, 119,4130-4135
56. Sha, C.-K.; Santhosh, K. C.; Lih, S.-H. a-Carbonyl Radical Cyclization Approach toward Angular Triquinanes:Total Synthesis of Enantiomerically Pure (-)-5-Oxosilphiperfol-6-ene. [J]. J. Org. Chem,1998,63,2699-2704.
57. Sha, C.-K.; Lee, F.-K.; Chang, C.-J. Tandem Radical Cyclizations Initiated with a-Carbonyl Radicals:First Total Synthesis of (+)-Paniculatine. [J].J. Am. Chem. Soc,1999,121, 9857-9876.
58. Mukai, C.; Kim, J.S.; Sonobe, H.; Hanaoka, M. Stereocomplementary Construction of Optically Active Bicyclo[4.3.0]nonenone Derivatives. [J]. J. Org. Chem,1999,64,6822-6832.
59. Nakayama, Kogure, A.;N.; Kitajima, M.; Takayama, H. First Asymmetric Total Syntheses of Fawcettimine-Type Lycopodium Alkaloids, Lycoposerramine-C and Phlegmariurine-A. [J]. Org. Lett,2009,11,5554-5557.
60. Canham, S.M.; France, D.J.; Overman, L.E. Total Synthesis of (+)-Sieboldine A. [J]. J. Am. Chem. Soc,2010,132,7876-7877.
61. Zhang, X.-M.; Tu, Y.-Q.; Zhang, F.-M.; Shao, H.; Meng, X. Total Synthesis of (±)-Alopecuridine and Its Biomimetic Transformation into (±)-Sieboldine A. [J]. Angew. Chem. Int. Ed,2011,50,3916-3919.
1. Zhu, D.-Y.; Jiang, S.-H.; Huang, M.-F.; Lin,L.-Z.; Cordell, G..A. Huperserratinine from Huperzia serrata. [J]. Phytochemistry,1994,36,1069-1072.
2. Morita, H.; Arisaka, M.; Yoshida, N.; Kobayashi, J. Serratezomines A-C, New Alkaloids from Lycopodium serratum var. serratum. [J]. J. Org. Chem,2000,65,6241-6245.
3. Hirasawa, Y.; Tanaka, T.; Kobayashi, J.; Kawahara, N.; Goda, Y,; Morita, H. Malycorins A-C, New Lycopodium Alkaloids from Lycopodium phlegmaria. [J]. Chem. Pharm. Bull,2008,56, 1473-1476.
4. Morita, H.; Kobayashi, J. A Biomimetic Transformation of Serratinine into Serratezomine A through a Modified Polonovski Reaction. [J]. J. Org. Chem,2002,67,5378-5381.
5. Harayama, T.; Ohtani, M.; Oki, M.; Inubushi, Y. Total synthesis of lycopodium alkaloid (±)-serratinine. [J]. J. Chem. Soc., Chem. Commun,1974,827-828.
6. Harayama, T.; Takatani, M.; Inubushi, Y. Stereoselective syntheses of lycopodium alkaloids, (±)-Fawcettimine and (±)-8-Deoxyserratinine. [J]. Tetrahedron Lett,1979,20,4307-4310.
7. Harayama, T.; Takatani, M.; Inubushi, Y. Total syntheses of the lycopodium alkaloids (±)-Fawcettimine and (±)-8-Deoxyserratinine. [J].Chem. Pharm. Bull,1980,28,2394-2402.
8. Caine, D.; Procter, K.; Camell, R.A. A Facile Synthesis of (-)-(R)-5-Methyl-2-cyclohexen-l-one and Related 2-Substituted Enones from (+)-Pulegone. [J]. J. Org. Chem,1984,49,2647-2648.
9. Bal, S.A.; Marfat, A.; Helquist, P. Cyclopentene and Cyclohexene Annulation via Copper-Catalyzed Conjugate Addition of Acetal-Containing Grignard Reagents. [J]. J. Org. Chem,1982,47,5045-5050.
10. Li, S.; Yamamura, S. Synthesis of the Tetracycfic ABCE Ring Subunit I, Bearing the 13-Membered Azacyde, of Manzamine A. [J]. Tetrahedron,1998,54,8691-8710.
11. Johansson, M.; Sterner, O. Synthesis of (+)-Galiellalactone. Absolute Configuration of Galiellalactone. [J]. Org. Lett,2001,3,2843-2845
12. Stowell, J.C.; Keith, D.R.; King, B.T.β-Haloacetals and ketals:2-(2-bromoethyl)-1,3-dioxane and 2,5,5-trimethyl-2-(2-bromoethyl)-1,3-dioxane. [J]. Organic Syntheses,1990,7,59-63.
13. Yang, Y.-R.; Shen, L.; Wei, K.; Zhao, Q.-S. Cyclization Approaching to (-)-Lycojapodine A: Synthesis of Two Unnatural Alkaloids. [J]. J. Org. Chem,2010,75,1317-1320.
14. Kan, T.; Fujiwara, A.; Kobayashi, H.; Fukuyama, T. Efficient macrocyclization by means of 2-nitrobenzenesulfonamide and total synthesis of lipogrammistin-A. [J]. Tetrahedron,2002,58, 6267-6276.
15. Fujiwara, A.; Kan, T.; Fukuyama, T. Total Synthesis of Lipogrammistin-A:Efficient Macrocyclization with 2-Nitrobenzenesulfonamide. [J]. Synlett,2000,11,1667-1669.
16. Kan, T.; Kobayashi, H.; Fukuyama, T. Efficient Synthesis of Medium-Sized Cyclic Amines by Means of 2-Nitrobenzenesulfonamide. [J]. Synlett,2002,5,697-699. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Org. Chem,1989,54, 1548-1562.
17. Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. An Efficient Catalytic Asymmetric Epoxidation Method. [J]. J. Am. Chem. Soc,1997,119,11224-11235.
2. a). Manske, R.H.F. The Alkaloids.; Academic Press:New York,1955,5,295-300. b). Maclean, D.B. The Alkaloids.; Academic Press:New York,1968,10,305-382. c). Ayer W.A. Trifonow, L.S. The Alkaloids.; Academic Press:New York,1994,45,233.
3.刘嘉森,俞超美,周有作,韩燕艺,吴凤梧,戚宝凤,朱元龙.石杉碱甲和石杉碱乙的化!学研究.[J].化学学报,1986,44,1035-1040.
4. Burnell, R. H. Lycopodium alkaloids. I. Extraction of alkaloids from Lycopodium fawcettii. [J] J. Chem. Soc,1959,3091-3093
5. a). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. Serratinine:A novel skeletal lycopodium alkaloid. [J]. Chem. Pharm. Bull,1968,16,82-91. b). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. The Plane Structure of Serratinine. [J]. Chem. Pharm. Bull, 1968,16,92-100. c). Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. The Plane Structure of Serratinine. [J]. Chem. Pharm. Bull,1968,16,101-112
6. Inubushi, Y.; Ishii, H.; Yasui, B.; Harayama, T.; Hosokawa, M.; Nishino, R.; Nakahara Y Constituents of domestic Lycopodium plants. Ⅶ. Alkaloid constituents of L. serratum var serratum f. serratumand L. serrarum var serratum f. intermedium. [J]. Yakugaku. Zasshi,1967, 87,1394-1404.
7. Ayer, W.A.; Altenkirk, B.; Fukazawa, Y. Alkaloids of Lycopodium alopecuroides L.-V:The structure of Alopecuridine. [J]. Tetrahedron,1974,30,4213-4214.
8. a). Castillo, M.; Morales, G.; Loyola, L. A.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. Paniculatine. A New Alkaloid from L. paniculatum Desvaux. [J]. Can. J. Chem,1975,53, 2513-2514. b). Castillo, M.; Morales, G.; Loyola, L.A.; Singh, I.; Calvo C.; Holland, H.L. MacLean, D. B. Paniculatine. The alkaloids of L. paniculatum and the structure of paniculatine. [J]. Can. J. Chem,1975,54,2900-2908.
9. Ayer, W.A.; Fukazawa, Y.; Singer, P. P. Lycoflexine, a new type of lycopodium alkaloid. [J]. Tetrahedron Lett,1973,14,5045-5048.
10. a) Ma, X.; Gang, D. R. The Lycopodium alkaloids. [J]. Nat. Prod. Rep.2004,21,752-772. b) Hirasawa, Y.; Kobayashi, J.; Morita, H. The Lycopodium alkaloids. [J]. Heterocycles,2009,77, 679-729.
11.Gao,W.Y.; Wang, B.D.; Li,Y.M.; Jiang, S.H.; Zhu, D.Y. Anew alkaloid and arbutin from the whole plant of Huperzia serrata. [J]. Chin. J. Chem,2000,18,614-616.
12.袁珊琴,赵毅民,冯锐.蛇足石杉新碱的结构鉴定.[J].药学学报2002,37,946-949
13. Tan, C.H.; Ma, X.Q.; Chen, G.F.; Zhu, D.Y. Huperzines S, T, and U:New Lycopodium alkaloids from Huperzia serrata. [J]. Can. J. Chem,2003,81,315-318.
14. Takayama, H. Katakawa, K. Kitajima, M. Yamaguchi, K. Aimi, N. Seven new Lycopodium alkaloids, lycoposerramines-C,-D,-E,-P,-Q,-S, and-U, from Lycopodium serratum Thunb. [J]. Tetrahedron Lett,2002,43,8307-8311.
15. Takayama, H.; Katakawa, K.; Kitajima, M.; Seki, H.; Yamaguchi, K.; Aimi, N. A New Type of Lycopodium Alkaloid, Lycoposerramine-A, from Lycopodium serratum Thunb. [J]. Org. Lett, 2001,3,4165-4167.
16. Katakawa, K.; Kitajima, M.; Aimi, N.; Seki, H.; Yamaguchi, K.; Furihata, K.; Harayama, T.; Takayama, H. Structure Elucidation and Synthesis of Lycoposerramine-B, a Novel Oxime-Containing Lycopodium Alkaloid from Lycopodium serratum Thunb. [J]. J. Org. Chem, 2005,70,658-663.
17. Katakawa, K.; Kogure, N.; Kitajima, M.; Takayama, H. A new Lycopodium alkaloid, Lycoposerramine-R, with a novel skeleton and three new faweettimine-related alkaloids from serratum. [J]. Helv. Chim. Aeta,2009,92,445-452.
18. Hirasawa, Y.; Morita, H.; Shiro, M.; Kobayashi, J. Sieboldine A, a Novel Tetracyclic Alkaloid from Lycopodium sieboldine, Inhibiting Acetylcholinesterase. [J]. Org. Lett,2003,5,3991.
19. Koyama, K.; Morita, H.; Hirasawa, Y.; Yoshinaga, M.; Hoshino, T.; Obara, Y.; Norimichi N.; Kobayashi, J. Lannotinidines A-G, new alkaloids from two species of Lycomdium. [J]. Tetrahedron,2005,61,3681-3690.
20. Kubota, T.; Sunaura, T.; Morita, H.; Mikami,Y;Hoshino,T.;Obara,Y.;Nakahata,N.;Kobayashi,J. Lycovatine A, a C16 N-type quaternary alkaloid from Lycopodium Clavatum var.Robustum. [J]. Heterocycles,2006,69,469-474.
21. He, J.; Chen, X.Q.; Li, M.M.; Zhao, Y.; Xu, G.; Cheng, X.; Peng, L.Y.; Xie, M.J.; Zheng, Y.T.; Wang, Y.P.; Zhao, Q.S. Lycojapodine A, a novel alkaloid from Lycopodium japonicum. [J]. Org. Lett,2009,11,1397-1400.
22. Zhao, F.W.; Sun, Q.Y.; Yang, F.M.; Hu, G.W.; Luo, J.F.; Tang, G.H.; Wang, Y.H.; Long, C.L. Palhinine A, a Novel Alkaloid from Palhinhaea cernua. [J]. Org. Lett,2010,12,3922-3925.
23.陈业高,刘怡君,蒋金和,刘波.石松类生物碱成分研究的新进展.[J].云南师范大学学学报,2010,30,12-24.
24.谭昌恒,朱大元.石松生物碱研究进展.[J].中国天然药物,2003,1,1-7.
25. Ayer, W.A.; Ma, Y.T.; Liu, J.S.; Huang, M.F.; Schultz, L.W.; Clardy, J. Macleanine, a unique type of dinitrogenous Lycopodiurn alkaloid. [J]. Can. J. Chem,1994,72,128-130.
26. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Am. Chem. Soc,1986,108,5022-5024.
27. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Org. Chem,1989,54,1548-1562.
28. Linghu, X.; Kennedy-Smith, J. J.; Toste, F. D. Total Synthesis of (+)-Fawcettimine. [J]. Angew. Chem. Int. Ed,2007,46,7671-7673.
29. Staben, S. T.; Kennedy-Smith, J. J.; Huang, D.; Corkey, B. K.; LaLonde, R. L.; Toste, F. D. Gold(I)-Catalyzed Cyclizations of Silyl Enol Ethers:Application to the Synthesis of (+)-Lycopladine A. [J]. Angew. Chem. Int. Ed,2006,45,5991-5994.
30. Kozaka, T.; Miyakoshi, N.; Mukai, C. Stereoselective Total Syntheses of Three Lycopodium Alkaloids, (-)-Magellanine, (+)-Magellaninone, and (+)-Paniculatine, Based on Two Pauson Khand Reactions. [J]. J. Org. Chem,2007,72,10147-10154.
31.Otsuka,Y.;Inagaki, F.; Mukai, C. Total Syntheses of (+)-Fawcettimine and (+)-Lycoposerramine B. [J].J. Org. Chem,2010,75,3430-3426.
32. Fang, J.; Ren, J.; Wang, Z. Sc(OTf)3-catalyzed smooth tandem [3+2] cycloaddition/ring opening of donor-acceptor cyclopropane 1,1-diesters with enol silyl ethers. [J]. Tetrahedron Lett, 2008,49,6659-6662.
33. Qu, J.-P.; Deng, C.; Zhou, J.; Sun, X.-L.; Tang, Y. Switchable Reactions of Cyclopropanes with Enol Silyl Ethers. Controllable Synthesis of Cyclopentanes and 1,6-Dicarbonyl Compounds. [J]. J. Org. Chem,2009,74,7684-7689.
34. Jung, M.E.; Chang, J.J. Enantiospecific Formal Total Synthesis of (+)-Fawcettimine. [J]. Org. Lett,2010,12,2962-2965.
35. Castillo, M.; Loyola, L. A.; Morales, G.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. The alkaloids of L. magellanicum and the structure of magellanine. [J]. Can. J. Chem,1976,54, 2893-2899.
36.Loyola, L.A.; Morales,G.; Castillo,M. Alkaloids of Lycopodium magellanicum. [J]. Phytochemistry,1979,18,1721-1723.
37. Hirst, G.C.; Johnson, T. O.; Jr.; Overman, L. E. First Total Synthesis of Lycopodium Alkaloids of the Magellanane Group. Enantioselective Total Syntheses of (-)-Magellanine and (+)-Magellaninone. [J].J. Am. Chem. Soc,1993,115,2992-2993.
38. Overman, L.E. Change as a key component in reaction design. The invention of cationic reactions of importance in synthesis. [J].Acc. Chem.Res,1992,25,352-359.
39. Overman, L.E. New reactions for forming heterocycles and their use in natural products synthesis. [J]. Aldrichmica Acta,1995,28,107-120.
40. Ando, S.; Minor, K.P.; Overman, L.E.; Ring-Enlarging Cyclohexane Annulations. [J]. J. Org. Chem,1997,62,6379-6387.
41. Paquette, L. A.; Friedrich, D.; Pinard, E.; Williams, J. P.; Laurent, D. St.; Roden, B. A. Total Synthesis of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone. [J]. J. Am. Chem. Soc,1993,115,4377-4378.
42. Williams, J. P.; Laurent, D.R.St.; Friedrich, D.; Pinard, E.; Roden, B. A.;Paquette, L. A. Total Synthesis of the Lycopodium Alkaloids Magellanine and Magellaninone by Three-fold Annulation of 2-Cyclopentenone. [J]. J. Am. Chem. Soc,1994,116,4689-4696.
43. Yen, C.F.; Liao, C.C.; Concise and Efficient Total Synthesis of Lycopodium Alkaloid Magellanine. [J]. Angew. Chem. Int. Ed,2002,41,4090-4093.
44. Hsu, D-S.; Rao, P.D.; Liao, C.C. Short and efficient route to substituted linear triquinanes from 2-methoxyphenols. [J]. Chem. Commun,1998,17,1795-1796.
45.Tsunoda, T.; Suzuki, M.; Noyori, R. A facile procedure for acetalization under aprotic conditions. [J]. Tetrahedron Lett,1980,21,1357-1358.
46.1reland, R.E.; Mueller, R.H.; Willard,A.K. The ester enolate Claisen rearrangement. Stereochemical control through stereoselective enolate formation. [J]. J. Am. Chem. Soc,1976, 98,2868-2877.
47. Chai, Y.; Hong, S-P.; Lindsay, H.A.; McFarland, C.; McIntosh, M.C. New aspects of the Ireland and related Claisen rearrangements. [J]. Tetrahedron,2000,58,2905-2928.
48. Khand, I.U.; Knox, G.R.; Pauson, P.L.; Watts, W.E.; Foreman, M.I. Organocobalt complexes. II.Reaction of acetylenehexacarbonyl dicobalt complexes, (RC2R1)Co2(CO)6, with norbornene and its derivatives. [J]. J. Chem. Soc, Perkin Trans,1973,977-981.
49.Schore, N.E.; Croudace, M.C. Preparation of bicyclo[3.3.0]oct-l-en-3-one and bicyclo[4.3.0]non-1(9)-en-8-one via intramolecular cyclization of α,ω-Enynes. [J]. J. Org. Chem,1981,46,5436-5438.
50. Ishizaki, M.; Niimi Y.; Hoshino, O. Formal total synthesis of (±)-magellanine. [J]. Tetrahedron Lett,2003,44,6029-6031.
51. Ishizaki, M.; Niimi, Y.; Hoshino, O.; Harab, H.; Takahashi, T. A formal total synthesis of Lycopodium alkaloid,(±)-magellanine, by using the intramolecular Pauson Khand reaction. [J]. Tetrahedron,2005,61,4053-4065.
52. Ryu, I.; Sonoda, N.; Curran, D. P. Tandem Radical Reactions of Carbon Monoxide, Isonitriles, and Other Reagent Equivalents of the Geminal Radical Acceptor/Radical Precursor Synthon. [J].Chem. Rev,1996,96,177-194.
53. Parsons, P. J.; Penkett, C. S.;Shell, A. J. Tandem Reactions in Organic Synthesis:Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. [J].Chem. Rev,1996,96,195-206.
54. Sha, C.-K.; Jean, T.-S.; Wang, D.-C. Intramolecular radical cyclization of silylacetylenic or olefinic a-iodo ketones:Application to the total synthesis of (±)-modhephene. [J]. Tetrahedron Lett,1990,31,3745-3748.
55. Sha, C.-K.; Chiu, R.-T.; Yang, C.-F.; Yao, N.-T.; Tseng, W.-H.; Liao, F.-L.; Wang, S.-L. Total Synthesis of (-)-Dendrobine via a-Carbonyl Radical Cyclization. [J]. J. Am. Chem. Soc,1997, 119,4130-4135
56. Sha, C.-K.; Santhosh, K. C.; Lih, S.-H. a-Carbonyl Radical Cyclization Approach toward Angular Triquinanes:Total Synthesis of Enantiomerically Pure (-)-5-Oxosilphiperfol-6-ene. [J]. J. Org. Chem,1998,63,2699-2704.
57. Sha, C.-K.; Lee, F.-K.; Chang, C.-J. Tandem Radical Cyclizations Initiated with a-Carbonyl Radicals:First Total Synthesis of (+)-Paniculatine. [J].J. Am. Chem. Soc,1999,121, 9857-9876.
58. Mukai, C.; Kim, J.S.; Sonobe, H.; Hanaoka, M. Stereocomplementary Construction of Optically Active Bicyclo[4.3.0]nonenone Derivatives. [J]. J. Org. Chem,1999,64,6822-6832.
59. Nakayama, Kogure, A.;N.; Kitajima, M.; Takayama, H. First Asymmetric Total Syntheses of Fawcettimine-Type Lycopodium Alkaloids, Lycoposerramine-C and Phlegmariurine-A. [J]. Org. Lett,2009,11,5554-5557.
60. Canham, S.M.; France, D.J.; Overman, L.E. Total Synthesis of (+)-Sieboldine A. [J]. J. Am. Chem. Soc,2010,132,7876-7877.
61. Zhang, X.-M.; Tu, Y.-Q.; Zhang, F.-M.; Shao, H.; Meng, X. Total Synthesis of (±)-Alopecuridine and Its Biomimetic Transformation into (±)-Sieboldine A. [J]. Angew. Chem. Int. Ed,2011,50,3916-3919.
1. Zhu, D.-Y.; Jiang, S.-H.; Huang, M.-F.; Lin,L.-Z.; Cordell, G..A. Huperserratinine from Huperzia serrata. [J]. Phytochemistry,1994,36,1069-1072.
2. Morita, H.; Arisaka, M.; Yoshida, N.; Kobayashi, J. Serratezomines A-C, New Alkaloids from Lycopodium serratum var. serratum. [J]. J. Org. Chem,2000,65,6241-6245.
3. Hirasawa, Y.; Tanaka, T.; Kobayashi, J.; Kawahara, N.; Goda, Y,; Morita, H. Malycorins A-C, New Lycopodium Alkaloids from Lycopodium phlegmaria. [J]. Chem. Pharm. Bull,2008,56, 1473-1476.
4. Morita, H.; Kobayashi, J. A Biomimetic Transformation of Serratinine into Serratezomine A through a Modified Polonovski Reaction. [J]. J. Org. Chem,2002,67,5378-5381.
5. Harayama, T.; Ohtani, M.; Oki, M.; Inubushi, Y. Total synthesis of lycopodium alkaloid (±)-serratinine. [J]. J. Chem. Soc., Chem. Commun,1974,827-828.
6. Harayama, T.; Takatani, M.; Inubushi, Y. Stereoselective syntheses of lycopodium alkaloids, (±)-Fawcettimine and (±)-8-Deoxyserratinine. [J]. Tetrahedron Lett,1979,20,4307-4310.
7. Harayama, T.; Takatani, M.; Inubushi, Y. Total syntheses of the lycopodium alkaloids (±)-Fawcettimine and (±)-8-Deoxyserratinine. [J].Chem. Pharm. Bull,1980,28,2394-2402.
8. Caine, D.; Procter, K.; Camell, R.A. A Facile Synthesis of (-)-(R)-5-Methyl-2-cyclohexen-l-one and Related 2-Substituted Enones from (+)-Pulegone. [J]. J. Org. Chem,1984,49,2647-2648.
9. Bal, S.A.; Marfat, A.; Helquist, P. Cyclopentene and Cyclohexene Annulation via Copper-Catalyzed Conjugate Addition of Acetal-Containing Grignard Reagents. [J]. J. Org. Chem,1982,47,5045-5050.
10. Li, S.; Yamamura, S. Synthesis of the Tetracycfic ABCE Ring Subunit I, Bearing the 13-Membered Azacyde, of Manzamine A. [J]. Tetrahedron,1998,54,8691-8710.
11. Johansson, M.; Sterner, O. Synthesis of (+)-Galiellalactone. Absolute Configuration of Galiellalactone. [J]. Org. Lett,2001,3,2843-2845
12. Stowell, J.C.; Keith, D.R.; King, B.T.β-Haloacetals and ketals:2-(2-bromoethyl)-1,3-dioxane and 2,5,5-trimethyl-2-(2-bromoethyl)-1,3-dioxane. [J]. Organic Syntheses,1990,7,59-63.
13. Yang, Y.-R.; Shen, L.; Wei, K.; Zhao, Q.-S. Cyclization Approaching to (-)-Lycojapodine A: Synthesis of Two Unnatural Alkaloids. [J]. J. Org. Chem,2010,75,1317-1320.
14. Kan, T.; Fujiwara, A.; Kobayashi, H.; Fukuyama, T. Efficient macrocyclization by means of 2-nitrobenzenesulfonamide and total synthesis of lipogrammistin-A. [J]. Tetrahedron,2002,58, 6267-6276.
15. Fujiwara, A.; Kan, T.; Fukuyama, T. Total Synthesis of Lipogrammistin-A:Efficient Macrocyclization with 2-Nitrobenzenesulfonamide. [J]. Synlett,2000,11,1667-1669.
16. Kan, T.; Kobayashi, H.; Fukuyama, T. Efficient Synthesis of Medium-Sized Cyclic Amines by Means of 2-Nitrobenzenesulfonamide. [J]. Synlett,2002,5,697-699. Heathcock, C. H.; Smith, K. M.; Blumenkopf, T. A.; Total Synthesis of (±)-Fawcettimine. [J]. J. Org. Chem,1989,54, 1548-1562.
17. Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. An Efficient Catalytic Asymmetric Epoxidation Method. [J]. J. Am. Chem. Soc,1997,119,11224-11235.