1
and 3 through a palladium-catalyzed three-component cou-
pling reaction.
methyl. Complete H and 13C chemical shift assignments
were made from the H-H COSY, HMQC, and HMBC
spectral data, and the resulting structure 2 was also supported
by NOEs observed between the diagnostic protons as shown
in Figure 1. Thus, the structure of 2 was assigned to a C13-
hydroxylated derivative of 14-nordehydrocacalohastine (5).7f,9
The methanol extract (10.9 g) of dried stem bark and
leaves of T. cuneata, which showed inhibition for mitochon-
drial and microsomal lipid peroxidation and weak antibacte-
rial activities, was partitioned between chloroform and water.
Purification of the chloroform extract was repeated by
column chromatography on silica gel. Further purification
by recycling preparative GPC (gel permeation chromatog-
raphy) provided two novel compounds 2 (3.7 mg, 0.034 wt
% yield) and 3 (5.6 mg, 0.051 wt % yield) along with a
known compound, maturinone (4).7,8
The molecular formula of compound 2 was established
as C15H14O3 by EI-HRMS [m/z 242.0942 (M+) -0.1 mmu].
The IR spectrum of 2 suggested the presence of a hydroxy
1
group (3363 cm-1). The H NMR spectrum of 2 in CDCl3
exhibited signals due to five sp2 methine protons at δ 8.21,
7.89, 7.69, 7.34, and 7.28, one benzenoid exo-methyl group
at δ 2.75, and one methoxy group at δ 4.36 (Table 1). The
Figure 1. Diagnostic NOEs observed in NOESY spectrum of 2.
The molecular formula of compound 3 was determined
to be C17H16O4 by EI-HRMS [m/z 284.1032 (M+) +0.5
mmu], and the molecular weight was found to be 42 mu
(C2H2O) more than that of 2. The IR spectrum of 3 indicated
the disappearance of a hydroxy band observed in 2 and the
appearance of an ester carbonyl band (1734 cm-1). In the
13C DEPT spectrum of 3, 15 signals were well resolved and
corresponded closely to those of 2 except for one carbonyl
carbon at δ 170.9 and one methyl at δ 20.9 (Table 2). The
1H NMR spectrum of 3 in CDCl3 was suggestive of one
additional methyl group with its resonance at δ 2.12 (3H,
s), and the downfield shift of the C13 methylene protons at
δ 4.95 in 2 to δ 5.36 in 3 compared with that of 2. From the
above results, the structure of 3 was assigned to an acetyl
derivative of the C13 hydroxy group in 2.
In preliminary biological tests, antioxidative activities were
evaluated for two new compounds, 2 and 3, and maturinone
(4)10 thus isolated from T. cuneata. It was found that they
were effective at preventing membrane lipid peroxidation.
The NADH-dependent mitochondrial and NADPH-depend-
ent microsomal lipid peroxidations were inhibited with IC50
values (µM) of 16.4 and 41.6 for 2, 59.7 and 54.3 for 3, and
71.7 and 74.4 for 4, respectively.11 These pharmacological
properties imply that some of the effects of the endemic
medicinal plant complex might be attributable to compounds
2-4 and that these natural products might be useful as lead
compounds in the field of medicinal chemistry. Therefore,
we planned total syntheses of the two new compounds 2
Table 1. 1H (500 MHz) and 13C (100 MHz) NMR and HMBC
Spectral Data for Compound 2 in CDCl3
a
position
δC
δH
HMBC (H f C)
1
2
3
4
5
6
7
8
120.4
124.1
125.3
134.0
130.8
107.7
120.5
142.7
138.9
124.9
129.8
144.2
56.1
8.21 (d, 8.6)
7.34 (dd, 8.6, 6.8)
7.28 (br d, 6.8)
C-3, 4, 5, 9
C-3, 4
C-1, 5, 15
7.89 (s)
C-4, 5, 7, 8
9
10
11
12
13
15
C9-OMe
7.69 (s)
C-7, 8, 11
C-7, 11, 12
C-3, 4, 5
C-9
4.95 (2H, s)
2.75 (3H, s)
4.36 (3H, s)
20.3
60.9
a Proton resonance multiplicities and coupling constants (J in hertz) are
given in parentheses.
15 carbon signals observed in the 13C NMR spectrum were
characterized by a DEPT experiment, which suggested that
2 had seven sp2 quaternary carbons, five sp2 methines, one
oxygenated methylene, one oxygenated methyl, and one
(4) Inman, W. D.; Luo, J.; Jolad, S. D.; King, S. R.; Cooper, R. J. Nat.
Prod. 1999, 62, 1088 and references therein.
(5) Gardun˜o-Ram´ırez, M. L.; Trejo, A.; Navarro, V.; Bye, R.; Linares,
E.; Delgado, G. J. Nat. Prod. 2001, 64, 432.
(6) Doe, M.; Hirai, Y.; Kinoshita, T.; Shibata, K.; Haraguchi, H.;
Morimoto, Y. Chem. Lett. 2004, 33, 714.
(7) Isolation: (a) Correa, J.; Romo, J. Tetrahedron 1966, 22, 685. (b)
Naya, K.; Miyoshi, Y.; Mori, H.; Takai, K.; Nakanishi, M. Chem. Lett.
1976, 73. (c) Joshi, K. C.; Singh, P.; Singh, G. Indian J. Chem. 1976, 14B,
637. (d) El-Emary, N. A.; Takemoto, T.; Kusano, G. Planta Med. 1980,
38, 161. (e) Torres, P.; Mancheno, B.; Chinchilla, R.; Asensi, M. C.; Grande,
M. Planta Med. 1988, 54, 257. (f) Torres, P.; Chinchilla, R.; Asensi, M.
C.; Grande, M. Phytochemistry 1989, 28, 3093. (g) Abdo, S.; de Bernardi,
M.; Marinoni, G.; Mellerio, G.; Samaniego, S.; Vidari, G.; Finzi, P. V.
Phytochemistry 1992, 31, 3937.
(8) Synthesis: (a) Joseph-Nathan, P.; Morales, J. J.; Romo, J. Tetrahedron
1966, 22, 301. (b) Brown, P. M.; Thomson, R. H. J. Chem. Soc., C 1969,
1184. (c) Ruiz, R. M.; Correa, J.; Maldonado, L. A. Bull. Soc. Chim. Fr.
1969, 3612. (d) Inouye, Y.; Uchida, Y.; Kakisawa, H. Bull. Chem. Soc.
Jpn. 1977, 50, 961. (e) Kobayashi, K.; Shimizu, H.; Sasaki, A.; Suginome,
H. J. Org. Chem. 1993, 58, 4614. (f) Cherkaoui, O.; Nebois, P.; Fillion, H.
Chem. Pharm. Bull. 1997, 45, 457.
(9) Synthesis: Hirai, Y.; Doe, M.; Kinoshita, T.; Morimoto, Y. Chem.
Lett. 2004, 33, 136.
(10) There has been no report on biological activities of maturinone (4).
(11) (a) Haraguchi, H.; Ishikawa, H.; Kubo, I. Planta Med. 1997, 63,
213. (b) Haraguchi, H.; Ishikawa, H.; Mizutani, K.; Tamura, Y.; Kinoshita,
T. Bioorg. Med. Chem. 1998, 6, 339.
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Org. Lett., Vol. 7, No. 9, 2005