LETTER
(10E,12E)-Diene-9-keto Acid
263
CDCl3 as reported in the literature,18 with the hope to ob-
serve some evidence for the (12E) configuration. To our
disappointment, the signals for the H-12 and H-13 protons
in the 1H NMR (500 MHz, CDCl3) spectrum for 5 turned
out very similar to that of 4 shown in Figure 3; it therefore
remained impossible to assign a (12E) configuration.
Subsequently, we found that Lu and co-workers19 had el-
egantly solved similar problems (but not related to glycer-
ides) by recording the 1H NMR spectra in benzene-d6, in
which the counterparts for the H-12 and H-13 protons of
4 (and 5) were resolved into a ‘dd’ and a ‘dt’ signal, re-
spectively, and thus proved the (E,E) configurations for
their conjugate diene-ketones.
J. Antibiot. 1995, 48, 363. (f) Wang, J.-F.; Dai, H.-Q.; Wei,
Y.-L.; Zhu, H.-J.; Yan, Y.-M.; Wang, Y.-H.; Long, C.-L.;
Zhong, H.-M.; Zhang, L.-X.; Cheng, Y.-X. Chem. Biodivers.
2012, 7, 2046. (g) Babady-Byla, W. H. Phytochemistry
1996, 42, 501. (h) Hirao, S.; Tara, K.; Kuwano, K.; Tanaka,
J.; Ishibashi, F. Biosci., Biotechnol., Biochem. 2012, 76, 372.
(i) Okuyama, E.; Hasegawa, T.; Matsushita, T.; Fujimoto,
H.; Ishibashi, M.; Yamazaki, M. Chem. Pharm. Bull. 2001,
49, 154.
(2) For example, see: (a) Mori, K. Tetrahedron 2012, 68, 8441.
(b) Stamatov, S. D.; Stawinski, J. Org. Biomol. Chem. 2007,
5, 3787. (c) Neef, A. B.; Schultz, C. Angew. Chem. Int. Ed.
2009, 48, 1498. (d) ter Horst, B.; Seshadri, C.; Sweet, L.;
Young, D. C.; Feringa, B. L.; Moody, D. B.; Minnaard, A. J.
J. Lipid Res. 2010, 51, 1017. (e) Batovska, D. I.; Tsubota, S.;
Kato, Y.; Asanoa, Y.; Ubukatab, M. Tetrahedron:
Asymmetry 2004, 15, 3551. (f) Rejzek, M.; Vacek, M.;
Wimmer, Z. Helv. Chim. Acta 2000, 83, 2756. (g) Li, A.;
Baker, D. L.; Tigyi, G.; Bittman, R. J. Org. Chem. 2006, 71,
629. (h) Kubiak, R. J.; Bruzik, K. S. J. Org. Chem. 2003, 68,
960. (i) Alcaraz, M.-L.; Peng, L.; Klotz, P.; Goeldner, M.
J. Org. Chem. 1996, 61, 192. (j) Vaique, E.; Guy, A.;
Couedelo, L.; Gosse, I.; Durand, T.; Cansell, M.; Pinet, S.
Tetrahedron 2010, 66, 8872. (k) Redden, P. R.; Lin, X.;
Horrobin, D. F. Chem. Phys. Lipids 1996, 79, 9.
Using the same technique, the H-12 and H-13 protons of
5 were also resolved from each other, and the distinct sig-
nals at δ 5.96 (dd, J = 15.2, 10.8 Hz, 1 H, H-12) and δ 5.79
(dt, J = 15.1, 7.2 Hz, 1 H, H-13) allowed for an unequiv-
ocal assignment of a (12E) configuration for 5 (and a
priori, 4).20 The long-missing piece of solid evidence for
the configuration of the C-12/C-13 double bond for acid 5
and related compounds is now finally available.
(3) Kim, K. H.; Moon, E.; Kim, S. Y.; Lee, K. R. Bull. Korean
Chem. Soc. 2010, 31, 2051.
In summary, the title monoglyceride 4 was synthesized
through a chiral pool based route, which allowed for a def-
inite confirmation of the structure as well as the configu-
rations assigned previously on the basis of spectroscopic
analyses/empirical rules. The present work also illustrates
the only (to date) synthetic entry to (10E,12E)-9-oxo-oc-
tadeca-10,12-dienoic acid (5), another biologically impor-
tant substance that has been involved in many lipids
studies, but which does not seem to have ever been fully
characterized, at least as far as the configuration of the C-
12/C-13 double bond is concerned. As the first piece of
solid evidence for the (12E) configuration for 5, and all
closely related compounds (including 4), is finally avail-
able by recording the 1H NMR spectra in benzene-d6,21 the
long-missing (although unknown) confusion/uncertainty
regarding the (12E) configuration of the related com-
pounds can thus be eliminated from now on.
(4) (a) Feng, S.; Saw, C. L.; Lee, Y. K.; Huang, D. J. Agric.
Food Chem. 2007, 55, 8589. (b) Vollenweider, S.; Weber,
H.; Stolz, S.; Chételat, A.; Farmer, E. Plant J. 2000, 24, 467.
(5) Watanebe, J.; Kawabata, J.; Kasai, T. Biosci., Biotechnol.,
Biochem. 1999, 63, 489.
(6) (a) Kawagishi, H.; Miyazawa, T.; Kume, H.; Arimoto, Y.;
Inakuma, T. J. Nat. Prod. 2002, 65, 1712. (b) Another study
(the only available data in the literature other than ref. 6a,
also measured in CDCl3) similarly gave δ 6.19–6.15 (m 2 H)
for the H-12 and H-13 protons, cf. ref. 8c.
(7) Chen, C.-Y.; Han, W.-B.; Chen, H.-J.; Wu, Y.-K.; Gao, P.
Eur. J. Org. Chem. 2012, 4311.
(8) Despite its broad existence in Nature and importance in
biology, no clear-cut routes to the (10E,12E) isomer exist to
date (to our knowledge). For routes to the other isomers, see:
(a) Tsuboi, S.; Maeda, S.; Takeda, A. Bull. Chem. Soc. Jpn.
1986, 59, 2050. (b) Iacazio, G. Chem. Phys. Lipids 2003,
125, 114. (c) Dufour, A.; Loonis, M. Chem. Phys. Lipids
2005, 138, 60. (d) Anterola, A.; Gobel, C.; Hornug, E.;
Sellhorn, G.; Feussner, I.; Frimes, H. Phytochemistry 2009,
70, 40.
Acknowledgment
(9) Guo, C.; Lu, X. J. Chem. Soc., Perkin Trans. 1 1993, 1921.
(10) (a) Sun, M.; Deng, Y.; Batyreva, E.; Sha, W.; Salomon, R.
G. J. Org. Chem. 2002, 67, 3575. (b) Jian, Y.-J.; Tang, C.-J.;
Wu, Y.-K. J. Org. Chem. 2007, 72, 4851.
(11) Schmidt, H. M.; Arens, J. F. Recl. Trav. Chim. Pays-Bas
1967, 86, 1138.
This work was supported by the National Basic Research Program
of China (the 973 Program, 2010CB833200), the National Natural
Science Foundation of China (21172247, 21032002, 20921091),
and the Chinese Academy of Sciences.
Supporting Information for this article is available online at
(12) (a) Nayyar, N. K.; Hutchison, D. R.; Martinelli, M. J. J. Org.
Chem. 1997, 62, 982. (b) Allard, M.; Barnes, K.; Chen, X.;
Cheung, Y.-Y.; Duffy, B.; Heap, C.; Inthavongsay, J.;
Johnson, M.; Krishnamoorthy, R.; Manley, C.; Steffke, S.;
Varughese, D.; Wang, R.; Wang, Y.; Schwartz, C. E.
Tetrahedron Lett. 2011, 52, 2623.
(13) (a) Smith, C. D.; Tchabanenko, K.; Adlington, R. M.;
Baldwin, J. E. Tetrahedron Lett. 2006, 47, 3209.
(b) Fukuoka, S.; Nanri, H.; Katsuki, T.; Yamaguchi, M.
Tetrahedron Lett. 1987, 28, 6205.
(14) Direct treatment of 9 with the anion of alkyne 7 led to
extensive formation of unidentified side products.
m
iotSrat
ungIifoop
r
t
References and Notes
(1) (a) Qi, S.-H.; Zhang, S.; Huang, J.-S.; Xiao, Z.-H.; Wu, J.;
Long, L.-J. Chem. Pharm. Bull. 2004, 52, 986. (b) Omura,
S.; Nakagawa, A.; Fukamachi, N.; Otaguro, K.; Kobayashi,
B. J. Antibiot. 1986, 39, 1180. (c) Kitahara, T.; Aono, S.;
Mori, K. Biosci. Biotechnol., Biochem. 1995, 59, 78.
(d) Zeng, X.; Xiang, L.; Li, C.-Y.; Wang, Y.; Qiu, G.;
Zhang, Z.-x.; He, X. Fitoterapia 2012, 83, 609. (e) Akeda,
Y.; Shibata, K.; Ping, X.; Tanaka, T.; Taniguchi, M.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 261–264