Lycopodine & Huperzine A Story of Lycopodium Alkaloids

Transcription

1 Lycopodine & Huperzine A Story of Lycopodium Alkaloids Reporter: Supervisor: Zhe Niu Prof. Yang Prof. Chen Prof. Tang 2014/12/3

2 Content Background Synthetic Studies of Lycopodine An AChEI Huperzine A Summury Acknowledgement 2

3 Content Background Introduction Structure Features & Classification Bioactivities Synthetic Studies of Lycopodine An AChEI Huperzine A Summury Acknowledgement 3

4 Background General Introduction Isoetes lacustris 水韭 Lycopodiella cernua 过山龙 4

5 Background Bioactivity of Lycopodium Alkaloids Lycopodium complanatum 扁枝石松 Potent Inhibitor of Acetylcholinesterase Treatment of Alzheimer s Disease First isolated by Karl Bödeker in 1881 千层塔 ( 跌打损伤草 ) 退热止血, 消肿止痛 治肺热吐血, 脓肿, 溃烂, 创伤久不愈合 常用中草药配方 Bödeker, K. Justus Liebigs Ann. Chem., 1881, 208, 363. Ma, X.; Gang, D. R. Nat. Prod. Rep., 2004, 21,

6 Background Stuctural Features & Classification Ma, X.; Gang, D. R. Nat. Prod. Rep., 2004, 21,

7 Content Background Synthetic Studies of Lacopodine An AChEI Huperzine A Summury Acknowledgement 7

8 Lycopodine Synthetic Approaches to Lycopodine Stork, G.; Kretchmer, R. A.; Schlessinger, R. H. J. Am. Chem. Soc., 1968, 90, Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. J. Am. Chem. Soc., 1978, 100, Kraus, G. A.; Hon, Y-S. J. Am. Chem. Soc., 1985, 107, Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem. Soc., 2008, 130,

9 Lycopodine Stork s Synthesis 17 steps (1.1%) Stork, G.; Kretchmer, R. A.; Schlessinger, R. H. J. Am. Chem. Soc., 1968, 90,

10 Lycopodine Heathcock s Synthesis Clark, R. D.; Heathcock, C. H. J. Org. Chem., 1976, 41, 636. Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. J. Am. Chem. Soc., 1978, 100, Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. J. Am. Chem. Soc., 1982, 104, steps (16.6% from 11) 10

11 Lycopodine Kraus s Synthesis 9 steps (25% from 11) Kraus, G. A.; Hon, Y-S. J. Am. Chem. Soc., 1985, 107,

12 Lycopodine Carter s Asymmetric Synthesis 11 steps (8% from 23) Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem. Soc., 2008, 130,

13 Lycopodine Synthetic Approaches to Lycopodine Stork, G.; Kretchmer, R. A.; Schlessinger, R. H. J. Am. Chem. Soc., 1968, 90, Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. J. Am. Chem. Soc., 1978, 100, Kraus, G. A.; Hon, Y-S. J. Am. Chem. Soc., 1985, 107, Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem. Soc., 2008, 130,

14 Lycopodine Additional Syntheses Padwa s Tandem Cyclization Sequence Grieco s Synthesis Padwa, A.; Brodney, M. A.; Marino, J. P.; Sheehan, S. M. J. Org. Chem., 1997, 62, 78. Grieco, P. A.; Dai, Y. J. Am. Chem. Soc., 1998, 120,

15 Content Background Synthetic Studies of Lycopodine An AChEI Huperzine A Summury Acknowledgement 15

16 Huperzine A Bioactivity of HupA 蛇足石杉 H. Serrata Tan, C.-H.; Zhu, D.-Y. Chin. J, Nat. Med., 2003, 1, 1. Ma, X.; Gang, D. R. Nat. Prod. Rep., 2004, 21,

17 Huperzine A Biogenitic Hypothesis Ma, X.; Gang, D. R. Nat. Prod. Rep., 2004, 21,

18 Huperzine A Biogenitic Hypothesis Ma, X.; Gang, D. R. Nat. Prod. Rep., 2004, 21,

19 Huperzine A Selected Synthetic Approaches to HuperzineA White, J. D.; Li, Y.; Kim, J.; Terinek, M. Org. Lett., 2013, 15, 882. Koshiba, T.; Yokoshima, S.; Fukuyama, T. Org. Lett., 2009, 11, Xia. Y.; Kozikowski, A. P. J. Am. Chem. Soc., 1989, 111, Ding, R.; Fu, J.-G.; Xu, G.- Q.; Sun, B.-F.; Lin, G.-Q. J. Org. Chem., 2014, 79,

20 Huperzine A White s Strategy 18 steps White, J. D.; Li, Y.; Kim, J.; Terinek, M. Org. Lett., 2013, 15,

21 Huperzine A Fukuyama s Approach 20 steps Koshiba, T.; Yokoshima, S.; Fukuyama, T. Org. Lett., 2009, 11,

22 Huperzine A Kozikowski s Tandem Cyclization 14 steps Xia. Y.; Kozikowski, A. P. J. Am. Chem. Soc., 1989, 111,

23 Huperzine A Lin s Synthesis 10 steps Ding, R.; Fu, J.-G.; Xu, G.- Q.; Sun, B.-F.; Lin, G.-Q. J. Org. Chem., 2014, 79,

24 Summary 24

25 Summary Lycopodium complanatum 扁枝石松 First isolated by Karl Bödeker in 1881 蛇足石杉 H. Serrata Isolated by Jiasen Liu in

26 Summary 26

27 Summary 千层塔青蒿五味子 27

28 Acknowledgenent Prof. Yang, Prof. Chen, Prof. Tang Mr. Yixin Han Members of Laboratory Everyone here Thank you for your attention!