Organic Letters
Letter
Scheme 3. Synthesis of Tricyclic Compound 20
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge on the
Experimental procedures and spectral data of compounds
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The analytics team at the Institute of Organic Chemistry and
Dr. J. Fohrer as well as Dr. G. Drager (for X-ray analysis) are
gratefully acknowledged for their support.
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REFERENCES
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(1) Meng, F.-Y.; Sun, J.-X.; Li, X.; Yu, H.-Y.; Li, S.-M.; Ruan, H.-L.
Org. Lett. 2011, 13, 1502−1505.
(2) Synthetic contributions were reported through a Ph.D. thesis
(3) (a) Chen, M.; Kilgore, N.; Lee, K.-H.; Chen, D.-F. J. Nat. Prod.
2006, 69, 1697−1701. (b) Kuo, Y.-H.; Li, S.-Y.; Wu, M.-D.; Huang, R.-
L.; Yang Kuo, L.-M.; Chen, C.-F. Chem. Pharm. Bull. 1999, 47, 1047−
1048.
(4) Xiao, W.-L.; Li, R.-T.; Huang, S.-X.; Pu, J.-X.; Sun, H.-D. Nat.
Figure 2. Configurational assignment of compound 20 via NOE
experiments.
Prod. Rep. 2008, 25, 871−891.
(5) Shi, Y.-M.; Xiao, W.-L.; Pu, J.-X.; Sun, H.-D. Nat. Prod. Rep. 2015,
32, 367−410.
(6) (a) Pemp, A.; Seifert, K. Tetrahedron Lett. 1997, 38, 2081−2084.
(b) Smith, A. B.; Mewshaw, R. J. Org. Chem. 1984, 49, 3685−3689.
(c) Jung, M. E.; Duclos, B. A. Tetrahedron 2006, 62, 9321−9334.
(d) Shigehisa, H.; Mizutani, T.; Tosaki, S.-y.; Ohshima, T.; Shibasaki,
M. Tetrahedron 2005, 61, 5057−5065. (e) Zhou, P.; Zhang, L.; Luo,
S.; Cheng, J.-P. J. Org. Chem. 2012, 77, 2526−2530.
(7) Liu, H.-J.; Yeh, W.-L.; Browne, E. N. Can. J. Chem. 1995, 73,
1135−1147.
proton 8a gave NOE contacts to the proton of interest (H12)
as well as to protons at C30 and C17. H12 showed cross signals
to the same proton at C17 and H8a. Due to the fixed
conformation of the tricyclic framework, the configuration at
C12 was confirmed as R. With compound 20 in hand, the
complex tricyclic framework of the natural product has been
successfully prepared; to complete the total synthesis of the
natural product, it is still needed to oxidize the bridgehead
carbon, install the side chains to the C ring, and invert the
stereochemistry of the oxygen in the A ring.
In conclusion, we have accomplished a route to a new
tricyclic carbon scaffold. As key steps, ring expansion and
pinacol coupling were used to build up these rings. Four of the
seven stereogenic centers of schiglautone A (1) were installed
in the desired configuration, and one secondary alcohol
requires inversion at the end of the synthesis. This core
structure of schiglautone A (1) was synthesized in a linear
sequence of 16 steps and 7.7% overall yield from building block
11. Further experiments to complete the total synthesis are
currently under investigation.
(8) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011−1013.
(9) Commandeur, M.; Commandeur, C.; Cossy, J. Org. Lett. 2011,
13, 6018−6021.
(10) (a) Sha, C.-K.; Young, J.-J.; Jean, T.-S. J. Org. Chem. 1987, 52,
3919−3920. (b) Peng, S.-Z.; Sha, C.-K. Org. Lett. 2015, 17, 3486−
3489.
(11) Zhong, Y.-L.; Shing, T. K. M. J. Org. Chem. 1997, 62, 2622−
2624.
(12) (a) Edmonds, D. J.; Johnston, D.; Procter, D. J. Chem. Rev.
2004, 104, 3371−3404. (b) Mitome, H.; Miyaoka, H.; Yamada, Y.
Tetrahedron Lett. 2000, 41, 8107−8110.
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