Organic Letters
Letter
Scheme 4. Completion of the Synthesis of Caesalpinnone A
ACKNOWLEDGMENTS
We are grateful for generous financial support from the
National Natural Science Foundation of China (21772156 and
■
2
1502151 to H.Z., 21702167 to Z.L., and 21702168 to Z.W.)
and the Fundamental Research Funds for the Central
Universities (2452017180 to H.Z.).
REFERENCES
■
(
1) For recent reviews, see: (a) Veitch, N. C.; Grayer, R. J. Nat. Prod.
Rep. 2011, 28, 1626−1695. (b) Smeriglio, A.; Calderaro, A.; Denaro,
M.; Lagana, G.; Bellocco, E. Curr. Med. Chem. 2019, 26, 5094−5107.
(
c) Tungmunnithum, D.; Thongboonyou, A.; Pholboon, A.;
Yangsabai, A. Medicines 2018, 5, 93. (d) McRae, J. M.; Yang, Q.;
Crawford, R. J.; Palombo, E. A. In Flavonoids: Biosynthesis, Biological
Effects and Dietary Sources; Keller, R. B., Eds.; Nova Science
Publishers: New York, 2009; pp 291−299.
(
2) Zhang, L.-J.; Bi, D.-W.; Hu, J.; Mu, W.-H.; Li, Y.-P.; Xia, G.-H.;
Yang, L.; Liang, X.-S.; Wang, L.-Q. Org. Lett. 2017, 19, 4315−4318.
3) Timmerman, J. C.; Sims, N. J.; Wood, J. L. J. Am. Chem. Soc.
019, 141, 10082−10090.
4) (a) Davis, T. L.; Hill, J. W. J. Am. Chem. Soc. 1929, 51, 493−504.
(
2
(
(
b) Kiehlmann, E.; Lauener, R. W. Can. J. Chem. 1989, 67, 335−344.
rearrangement process. Treating 9 with trans-cinnamic acid in
the presence of EDC·HCl and DMAP resulted in the
formation of ester 20, which was irradiated under a 500 W
mercury lamp in benzene for 15 h, giving caesalpinnone A (1)
in 33% yield along with the deacylation product phenol 9 in
(c) Pelish, H. E.; Westwood, N. J.; Feng, Y.; Kirchhausen, T.; Shair,
M. D. J. Am. Chem. Soc. 2001, 123, 6740−6741.
(
5) Zhang, Y.; Liu, D.; Li, Y.; Cao, X.-P. Chin. J. Chem. 2005, 23,
1
453−1456.
6) (a) Selenski, C.; Pettus, T. R. R. J. Org. Chem. 2004, 69, 9196−
203. (b) Green, J. C.; Jimenez-Alonso, S.; Brown, E. R.; Pettus, T. R.
(
9
1
3
6
R. Org. Lett. 2011, 13, 5500−5503. (c) Gharpure, S. J.;
Sathiyanarayanan, A. M.; Vuram, P. K. RSC Adv. 2013, 3, 18279−
2
18282. (d) Wang, C.-S.; Cheng, Y.-C.; Zhou, J.; Mei, G.-J.; Wang, S.-
In summary, we have accomplished the total synthesis of
caesalpinnone A through an oxa-[4 + 2] cycloaddition
followed by a trans-selective nucleophilic substitution to
construct the 2,4-trans-flavonoid core, a sequential dearomative
oxidation/deallylation/oxa-Michael reaction to establish the
characteristic bridged ketal, and a photo-Fries rearrangement
to introduce the cinnamyl chain. Additionally, we have made
an attempt to achieve the asymmetric oxa-[4 + 2] cyclo-
addition, although the ee value was not high (up to 38% ee).
Improvement of the enantioselectivity of the oxa-[4 + 2]
cycloaddition as well as evaluation of the biological activities of
the synthesized compounds would be the focus of our future
work.
L.; Shi, F. J. Org. Chem. 2018, 83, 13861−13873. (e) Tanaka, K.;
Omata, D.; Asada, Y.; Hoshino, Y.; Honda, K. J. Org. Chem. 2019, 84,
10669−10678.
(
(
(
7) Wang, Z.; Sun, J. Org. Lett. 2017, 19, 2334−2337.
8) Brown, D. S.; Ley, S. V. Tetrahedron Lett. 1988, 29, 4869−4872.
9) Evans, D. A.; Kværnø, L.; Dunn, T. B.; Beauchemin, A.; Raymer,
B.; Mulder, J. A.; Olhava, E. J.; Juhl, M.; Kagechika, K.; Favor, D. A. J.
Am. Chem. Soc. 2008, 130, 16295−16309.
(
(
10) Merz, A.; Rauschel, M. Synthesis 1993, 1993, 797−802.
11) Pitsinos, E. N.; Cruz, A. Org. Lett. 2005, 7, 2245−2248.
(
b) Ohkata, K.; Tamura, Y.; Shetuni, B. B.; Takagi, R.; Miyanaga, W.;
Kojima, S.; Paquette, L. A. J. Am. Chem. Soc. 2004, 126, 16783−
16792. (c) Mitra, P.; Behera, B.; Maiti, T. K.; Mal, D. J. Org. Chem.
2013, 78, 9748−9757.
(12) (a) Tsukamoto, H.; Suzuki, T.; Kondo, Y. Synlett 2007, 2007,
3
131−3136. (b) Tsukamoto, H.; Kondo, Y. Synlett 2003, 7, 1061−
ASSOCIATED CONTENT
Supporting Information
■
1063.
*
S
(
13) (a) Toldo, J. M.; Barbatti, M.; Goncalves, P. F. B. Phys. Chem.
Chem. Phys. 2017, 19, 19103−19108. (b) Magnus, P.; Lescop, C.
Tetrahedron Lett. 2001, 42, 7193−7196.
Experimental procedures and physical properties of the
AUTHOR INFORMATION
■
ORCID
Author Contributions
†
Z.L. and Y.M. contributed equally.
Notes
The authors declare no competing financial interest.
C
Org. Lett. XXXX, XXX, XXX−XXX