744
S. Claessens et al.
LETTER
OH
OH
O
O
References
OH
O
O
N
(1) For a review, see: Mitchell, A. S.; Russell, R. A.
N
N
Tetrahedron Lett. 1995, 51, 5207.
(2) Selected examples: (a) Kaiser, F.; Schwink, L.; Velder, J.;
Schmalz, H. G. Tetrahedron 2003, 59, 3201. (b) Couche,
E.; Fkyerat, A.; Tabacchi, R. Helv. Chim. Acta 2003, 86,
210. (c) Ge, P.; Russell, R. A. Tetrahedron 1997, 53, 17477.
(3) (a) Claessens, S.; Naidoo, D.; Mulholland, D.; Verschaeve,
L.; van Staden, J.; De Kimpe, N. Synlett 2006, 621. (b) For
a review on pentalongin, see: Claessens, S.; Verniest, G.;
Jacobs, J.; Van Hende, E.; Habonimana, P.; Nguyen, V. T.;
Van Puyvelde, L.; De Kimpe, N. Synlett 2007, in press.
(4) Nguyen, V. T.; Verniest, G.; Claessens, S.; De Kimpe, N.
Tetrahedron 2005, 61, 2295; and references cited therein.
(5) Koyama, J.; Morita, I.; Kobayashi, N.; Osakai, T.; Usuki, Y.;
Taniguchi, M. Bioorg. Med. Chem. Lett. 2005, 15, 1079.
(6) Koyama, J.; Morita, I.; Kobayashi, N.; Osakai, T.; Hotta, H.;
Takayasu, J.; Nishino, H.; Tokuda, H. Cancer Lett. 2004,
212, 1.
(7) (a) Camacho, M. R.; Phillipson, J. D.; Croft, S. L.; Yardley,
V.; Solis, P. N. Planta Med. 2004, 70, 70. (b) Solis, P. N.;
Lang’at, C.; Gupta, M. P.; Kirby, G. C.; Warhurst, D. C.;
Phillipson, J. D. Planta Med. 1995, 61, 62.
(8) Nok, A. J. Cell Biochem. Funct. 2002, 20, 205.
(9) Khanapure, S. P.; Biehl, E. R. Heterocycles 1988, 27, 2643.
(10) Koyama, J.; Morita, I.; Kobayashi, N.; Osakai, T.; Hotta, H.;
Takayasu, J.; Nishino, H.; Tokuda, H. Cancer Lett. 2004, 1.
(11) Koyama, J.; Morita, I.; Kobayashi, N.; Osakai, T.; Usuki, Y.;
Taniguchi, M. Bioorg. Med. Chem. Lett. 2005, 15, 1079.
(12) Evans, D. A.; Campos, K. R.; Tedrow, J. S.; Michael, F. E.;
Gagne, M. R. J. Org. Chem. 1999, 64, 2994.
O
OH
28
O
27
29
Figure 1
phthalide 6 and pyridone 19g gave a complex mixture,
from which the 2-aza-anthraquinone could not be isolated.
Furthermore, some electronic properties and the Ghose–
Crippen log P of these compounds 26a–e were calculated
using the PM3 method.10,11 Changing the alkyl group will
not influence much the electronic properties but has a
great influence on the log P value. Comparison with com-
pounds known to have very good physiological activities
27–29 (Figure 1)10,11 shows that our compounds are prom-
ising. The charges at the carbonyl (C-10 and O-2) show
comparable behavior for anti-EBV-EA. Compound 26a
shows a very promising octanol–water partition coeffi-
cient (log P) for antimicrobial activity. Therefore, further
research is going on in order to investigate the bioactivi-
ties of these compounds.
Acknowledgment
This work was financially supported by the Flemish Institute for the
Promotion of Scientific-Technological Research in Industry (IWT)
and the Research Foundation – Flanders (FWO – Vlaanderen).
(13) (a) Kraus, G. A.; Sugimoti, H. Tetrahedron Lett. 1978,
2263. (b) Kraus, G. A.; Cho, H.; Crowley, S.; Roth, B.;
Sugimoto, H.; Prugh, S. J. Org. Chem. 1983, 48, 3499.
(14) (a) Gould, S. J.; Melville, C. R. Tetrahedron Lett. 1997, 38,
1473. (b) Cone, M. C.; Melville, C. R.; Gore, M. P.; Gould,
S. J. J. Org. Chem. 1993, 58, 1058.
(15) Dey, S.; Mal, D. Tetrahedron Lett. 2005, 46, 5483.
(16) For a review of the subject, see: Ciufolini, M. A.; Hermann,
C. Y. W.; Dong, Q.; Shimizu, T.; Swaminathan, S.; Xi, N.
Synlett 1998, 105.
(17) Haukaas, M. H.; O’Doherty, G. A. Org. Lett. 2001, 3, 401.
(18) Padwa, A.; Zanka, A.; Cassidy, M. P.; Harris, J. M.
Tetrahedron 2003, 59, 4939.
Synlett 2007, No. 5, 741–744 © Thieme Stuttgart · New York