R. Devulapally, Y.-S. Hon / Tetrahedron Letters 52 (2011) 3183–3185
3185
OMe
O
OMe
OMe
O
OMe
OH
OMe
12 (5%)
OEt
OEt
4
OEt
Cl
a
b
c
OEt
O
OMe
5
OMe
11
OMe
4
OMe
Me OH
OMe
HO
Me
O
O
OMe
d
e
3
(61%)
OMe
13
(
)-Zenkequinone B (1)
Scheme 4. Synthesis of ( )-zenkequinone B (1). Reagents and conditions: (a) 7, LDA, n-Bu4NI, THF, À78 °C to rt, 8 h; 3 N HCl, 0 °C to rt, 1 h, 90%; (b) NaBH4, THF/MeOH (4:1),
0 °C to rt, 5 h, 96%; (c) TiCl4, CH2Cl2, 0 °C, 20 min; (d) CeCl3, MeMgBr, THF, À78 to À20 °C, 4 h, 78%; (e) NBS, H2O, THF, rt, 10 min, 98%.
2. (a) Lenta, B. N.; Vonthron-Senecheau, C.; Soh, R. F.; Tantangmo, F.; Ngouela, S.;
comparing the spectral data with the reported natural (À)-zenk-
Kaiser, M.; Tsamo, E.; Anton, R.; Weniger, B. J. Ethnopharmacol. 2007, 111, 8–12;
(b) Lenta, B. N.; Weniger, B.; Antheaume, C.; Noungoue, D. T.; Ngouela, S.; Assob,
equinone B data.2b
In summary, we have successfully achieved the first total syn-
thesis of antimicrobial natural product ( )-zenkequinone B (1) by
using the TiCl4-promoted Friedel–Crafts type intramolecular cycli-
zation for the preparation of the key intermediate 3. The overall
yield of the synthesis of ( )-zenkequinone B was 40.3% from the
2-(chloromethyl)-9,10-dimethoxyanthracene (5).
J. C. N.; Vonthron-Senecheau, C.; Fokou, P. A.; Devkota, K. P.; Tsamo, E.; Sewald,
N. Phytochemistry 2007, 68, 1595–1599.
3. (a) Hon, Y. S.; Devulapally, R. Tetrahedron Lett. 2009, 50, 2831–2834; (b) Hon, Y.
S.; Devulapally, R. Tetrahedron Lett. 2009, 50, 5713–5715.
4. To the best of our knowledge benzylic carbanion of the compound 5 has not
been reported to date.
5. The 2-(chloromethyl)-9,10-dimethoxyanthracene (5) was prepared from
commercially available 2-hydroxymethylanthraquinone in two steps by using
the procedure reported by Jiang, which involves the reduction/methylation of 2-
hydroxymethylanthraquinone with n-Bu4NBr, Na2S2O4 followed by addition of
NaOH and MeI to give the 2-(hydroxymethyl)-9,10-dimethoxyanthracene.
Chlorination of 2-(hydroxymethyl)-9,10-dimethoxyanthracene using SOCl2
gave the 2-(chloromethyl)-9,10-dimethoxyanthracene (5) in good yield; see:
Jiang, H.; Xu, H.; Ye, J. J. Chem. Soc., Perkin Trans. 2, 2000, 925–930.
6. Page, P.; Blonski, C.; Perie, J. Tetrahedron 1996, 52, 1557–1572.
7. The methacrolein diethyl acetal (10) was prepared from the commercially
available methacrolein using the procedure reported by Bischofberger, see:
Bischofberger, N.; Waldmann, H.; Saito, T.; Simon, E. S.; Watson Lees, W.;
Bednarski, M. D.; Whitesides, G. M. J. Org. Chem. 1988, 53, 3457–3465.
8. (a) The inability to obtain lithium enolate of the pyruvaldehyde diethyl acetal
(8) using LDA prompted us to prepare iminoacetal 7; (b) The iminoacetal 7 was
prepared using a similar procedure reported by Tian et al. See: Tian, S.-K.; Hong,
R.; Deng, L. J. Am. Chem. Soc. 2003, 125, 9900–9901.
Acknowledgments
We are grateful to the National Science Council (NSC) and
National Chung Cheng University for the financial support.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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