Synthesis of Piperidin-2-yl and Pyrrolidin-2-yl Flavonoid Alkaloids
Acknowledgments
Financial support from the Centre National de la Recherche Sci-
entifique (CNRS) is gratefully acknowledged. T. B. N. thanks the
Institut de Chimie des Substances Naturelles (ICSN) for a postdoc-
toral fellowship.
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Figure 3. NOESY correlation for 1,3-cis and 1,3-trans of 11cc.
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Scheme 4. One-pot synthesis of N-demethylisoficine.
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Conclusions
In summary, an efficient phenolic Mannich reaction in-
volving the use of cyclic imines or iminium salts as electro-
philes has been developed. When chrysin was used as the
nucleophile, both C-6 and C-8 regioisomers were accessible
by changing the reaction conditions. The power of this reac-
tion is illustrated in the one-pot synthesis of N-demethylca-
pitavine (1), capitavine (2), isoficine (3), N,O-didemeth-
ylbuchenavianine (9a), and their analogues. The conditions
were successfully extended to a variety of phenols. The
method should find application in the diversity-oriented
synthesis of a library of 2-flavonoid alkaloids for the study
of structure–activity relationships of this class of natural
products. Work towards this direction is ongoing in our lab-
oratory.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, product characterization, and copies
Received: September 8, 2011
Published Online: October 31, 2011
1
of the H and 13C NMR spectra.
Eur. J. Org. Chem. 2011, 7076–7079
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