Journal of the American Chemical Society
Communication
Scheme 4. Bioinspired Cascade Cyclization
ASSOCIATED CONTENT
* Supporting Information
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S
Experimental procedures, copies of H and 13C NMR spectral
data for synthetic (+)-flabellidine (2), (−)-lycodine (3),
compounds 14−21, 23a−26, S1, S2, and S5, and CIF files
for 24, 25, and S5. This material is available free of charge via
1
AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI Grant Numbers
25293023 and 25460005.
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REFERENCES
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(1) For some recent examples of the total synthesis of Lycopodium
alkaloids, see: (a) Yuan, C.; Chang, C.-T.; Axelrod, A.; Siegel, D. J. Am.
Chem. Soc. 2010, 132, 5924. (b) Canham, S. M.; France, D. J.;
Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876. (c) Liau, B. B.;
Shair, M. D. J. Am. Chem. Soc. 2010, 132, 9594. (d) Ramharter, J.;
Weinstabl, H.; Mulzer, J. J. Am. Chem. Soc. 2010, 132, 14338.
(e) Laemmerhold, K. M.; Breit, B. Angew. Chem., Int. Ed. 2010, 49,
2367. (f) Yang, H.; Carter, R. G. J. Org. Chem. 2010, 75, 4929.
(g) Nishimura, T.; Unni, A. K.; Yokoshima, S.; Fukuyama, T. J. Am.
Chem. Soc. 2011, 133, 418. (h) Zhang, X.-M.; Tu, Y.-Q.; Zhang, F.-M.;
Shao, H.; Meng, X. Angew. Chem., Int. Ed. 2011, 50, 3916.
(i) Nakayama, A.; Kogure, N.; Kitajima, M.; Takayama, H. Angew.
Chem., Int. Ed. 2011, 50, 8025. (j) Li, H.; Wang, X.; Lei, X. Angew.
Chem., Int. Ed. 2012, 51, 491. (k) Shimada, N.; Abe, Y.; Yokoshima, S.;
Fukuyama, T. Angew. Chem., Int. Ed. 2012, 51, 11824. (l) Ge, H. M.;
Zhang, L.-D.; Tan, R. X.; Yao, Z.-J. J. Am. Chem. Soc. 2012, 134, 12323.
(m) Pan, G.; Williams, R. M. J. Org. Chem. 2012, 77, 4801.
(n) Newton, J. N.; Fischer, D. F.; Sarpong, R. Angew. Chem., Int. Ed.
2013, 52, 1726. (o) Hou, S.-H.; Tu, Y.-Q.; Liu, L.; Zhang, F.-M.;
Wang, S.-H.; Zhang, X.-M. Angew. Chem., Int. Ed. 2013, 52, 11373.
(p) Nishimura, T.; Unni, A. K.; Yokoshima, S.; Fukuyama, T. J. Am.
Chem. Soc. 2013, 135, 3243. (q) Yang, Y.; Haskins, C. W.; Zhang, W.;
Low, P. L.; Dai, M. Angew. Chem., Int. Ed. 2014, 53, 3922.
Scheme 5. Syntheses of (+)-Flabellidine (2) and
(−)-Lycodine (3)
α
(2) For recent reviews on Lycopodium alkaloids, see: (a) Ayer, W. A.;
Trifonov, L. S. In The Alkaloids; Cordell, G. A., Brossi, A., Eds.;
Academic Press: New York, 1994; Vol. 45, pp 233−274. (b) Ma, X.;
Gang, D. R. Nat. Prod. Rep. 2004, 21, 752. (c) Kobayashi, J.; Morita, H.
In The Alkaloids; Cordell, G. A., Ed.; Academic Press: New York, 2005;
Vol. 61, pp 1−57. (d) Hirasawa, Y.; Kobayashi, J.; Morita, H.
Heterocycles 2009, 77, 679. (e) Nakayama, A.; Kitajima, M.; Takayama,
H. Synlett 2012, 23, 2014. (f) Kitajima, M.; Takayama, H. In Topics in
Current Chemistry; Knolker, H.-J., Ed.; Springer: Berlin, 2012; Vol. 309,
̈
pp 1−31. (g) Siengalewicz, P.; Mulzer, J.; Rinner, U. The Alkaloids;
Knolker, H.-J., Ed.; Elsevier: Amsterdam, 2013, Vol. 72, pp 1−151.
̈
(h) Murphy, R. A.; Sarpong, R. Chem.Eur. J. 2014, 20, 42.
(3) (a) Liu, J.-S.; Zhu, Y.-L.; Yu, C.-M.; Zhou, Y.-Z.; Han, Y.-Y.; Wu,
F.-W.; Qi, B.-F. Can. J. Chem. 1986, 64, 837. (b) Kozikowski, A. P.;
Tuckmantel, W. Acc. Chem. Res. 1999, 32, 641.
̈
(4) (a) Manske, R. H. F.; Marion, L. Can. J. Res. 1942, 20 (Sec B), 87.
(b) Alam, S. N.; Adams, K. A. H.; MacLean, D. B. Can. J. Chem. 1964,
42, 2456.
(5) (a) Anet, F. A. L.; Eves, C. R. Can. J. Chem. 1958, 36, 902.
(b) Ayer, W. A.; Iverach, G. G. Can. J. Chem. 1960, 38, 1823.
(6) (a) Kleinman, E. F.; Heathcock, C. H. Tetrahedron Lett. 1979, 20,
4125. (b) Heathcock, C. H.; Kleinman, E. F.; Binkley, E. S. J. Am.
Chem. Soc. 1982, 104, 1054. (c) Tsukano, C.; Zhao, L.; Takemoto, Y.;
Hirama, M. Eur. J. Org. Chem. 2010, 4198. (d) Fischer, D. F.; Sarpong,
α
Reagents and conditions: (a) Pd(OH)2/C, H2 (1 atm), Boc2O,
AcOEt/MeOH (2:1), rt, 26 (55%) and 27 (21%); (b) TFA, CH2Cl2,
rt; (c) AcCl, Et3N, THF, −78 °C, 88% (2 steps); (d) IBX, DMSO, 45
°C, 62% (2 steps).
C
dx.doi.org/10.1021/ja507016g | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX