H. Imagawa et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2089–2093
2093
Figure 7. An analysis of the localization of neovibsanin derivatives inside a PC12 cell by using 4 as a fluorescent molecular probe. Left picture: PC12 cell after 24 h of the
culture with 40 M 4 and 10 ng/mL NGF. Compound 4 was identified as small-blue particles. Middle picture: PC12 cell after 48 h. Right picture: PC12 cell after 72 h. Note that
l
the fluorescent molecule 4 (blue particles) has accumulated inside each prominence.
Kawazu, K.; Fukuyama, Y. Tetrahedron Lett. 1999, 40, 6261; (c) Kubo, M.; Chen,
I.-S.; Fukuyama, Y. Chem. Pharm. Bull. 2001, 49, 242; (d) Fukuyama, Y.; Kubo,
M.; Minami, H.; Yuasa, H.; Matsuo, A.; Fujii, T.; Morisaki, M.; Harada, K. Chem.
Pharm. Bull. 2005, 53, 72; (e) Fukuyama, Y.; Fujii, H.; Minami, H.; Takahashi, H.;
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assembled at the neck of each small prominence (Fig. 7, middle
picture). Significant morphological changes were observed after
72 h. Elongation of the prominences, where the fluorescent mole-
cules accumulated, became particularly noticeable (Fig. 7, right
picture). These results show the neovibsanins accumulate in the
prominences.
In conclusion, the simple structure of neovibsanins required for
maintaining the neurite outgrowth activities and the localization
of neovibsanin derivatives inside the PC12 cell were revealed. We
are currently attempting to synthesize a photo-affinity labeled
probe for further mechanistic studies.
3. (a) Gallen, M. J.; Williams, C. M. Org. Lett. 2008, 10, 713; (b) Chen, A. P. J.;
Williams, C. M. Org. Lett. 2008, 10, 3441.
4. (a) Imagawa, H.; Saijo, H.; Kurisaki, T.; Yamamoto, H.; Kubo, M.; Fukuyama, Y.;
Nishizawa, M. Org. Lett. 2009, 11, 1253; (b) Esumi, T.; Mori, T.; Zhao, M.; Toyota,
M.; Fukuyama, Y. Org. Lett. 2010, 12, 888.
5. Mehta, G.; Bhat, B. A. Tetrahedron Lett. 2009, 50, 2474.
6. Gatri, R.; Gaïed, M. M. E. Tetrahedron Lett. 2002, 43, 7835.
7. Koide, K.; Meta, C. T. Org. Lett. 2004, 11, 1785.
8. Crystallographic data (excluding structure factors) for the structures of 6 have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 832773. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2
1EZ UK (Fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
9. Lloyd, A. G.; Arthur, S. T. Proc. Natl. Acad. Sci. U.S.A. 1976, 73, 2424.
10. This position was numbered based on the natural neovibsanin skeleton.
11. Smith, A. B., III; Dorsey, B. D.; Ohba, M.; Lupo, A. T., Jr.; Malamas, M. S. J. Org.
Chem. 1988, 53, 4314.
Acknowledgments
This study was financially supported by a Grant-in-Aid for Sci-
entific Research (C) (23590033) from the Ministry of Education,
Culture, Sports, Science and Technology of the Japanese Govern-
ment, and a MEXT.SENRYAKU.
12. Gatri, R.; Moncef, M.; Gaïed, E. Tetrahedron Lett. 2002, 43, 7835.
13. A mixture of stereoisomer at acetal position was used for the assay without
separation.
Supplementary data
14. An asymmetric version of this Diels-Alder reaction was recently reported.
Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122,
4243.
15. Narasimhan, N. S.; Mali, R. S. Synthesis 1975, 12, 796.
16. In the previous synthetic study of neovibsanin B, we have found that 2-
methoxy benzyl ether, which have a coordination ability, is advantageous for
subsequent regioselective alkylation.
Supplementary data associated with this article can be found, in
include MOL files and InChiKeys of the most important compounds
described in this article.
17. Guibe, F. Tetrahedron 1997, 53, 13509.
18. We developed this deprotection condition in previous total synthesis of 2 (Ref.
4a).
19. (a) Hermanand, B. A.; Fernandez, S. M. Biochem. Biophys. Res. Commun. 1981,
103, 1112; (b) Goya, S.; Takadate, A.; Fujino, H.; Otagiri, M.; Uekama, K. Chem.
Pharm. Bull. 1982, 30, 1363.
References and notes
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