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In conclusion, we have completed the total synthesis of
(+)-gambieric acid A (1) for the first time by exploiting
synthetic methodologies developed within our laboratory. The
chemistry described herein opens up avenue for the preparation
of synthetic analogues that would be helpful for addressing the
biological profile of 1, which is uniquely different from that of
ion channel-activating polycyclic ether neurotoxins despite the
high structural similarity shared among this class of natural
products. This study also demonstrated the vital role of total
synthesis in the structure determination of complex natural
products.
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ASSOCIATED CONTENT
* Supporting Information
■
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Experimental procedures and spectroscopic data for all new
compounds and copies of 1H and 13C NMR spectra for selected
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
(19) Sasaki, M.; Honda, S.; Noguchi, T.; Takakura, H.; Tachibana, K.
Synlett 2000, 838−840.
Notes
The authors declare no competing financial interests.
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Soc., Chem. Commun. 1989, 1344−1345.
ACKNOWLEDGMENTS
■
(21) Myers, A. G.; Zheng, B.; Movassaghi, M. J. Org. Chem. 1997, 62,
7507−7507.
We thank Professor Michio Murata (Osaka University) for
1
providing us with copies of H and 13C NMR spectra of the
(22) See the Supporting Information for details.
(23) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953−956.
authentic sample of (+)-gambieric acid A, Professor Hiroshi
Nagai (Tokyo University of Marine Science and Technology)
for his useful suggestions, and Dr. Yuko Cho (Tohoku
University) for her instructions in antifungal activity assay.
This work was financially supported in part by Grants-in-Aid
(Nos. 21241050, 23681045, 23102016, and 24102517) from
MEXT, Japan. Astellas Foundation for Research on Metabolic
Disorders and Banyu Life Science Foundation International are
acknowledged for financial support. K.I. is a recipient of the
Research Fellowship for Young Scientists from JSPS.
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