Tetranortriterpenoids from Cipadessa baccifera

Article abstract of DOI:10.1021/np070229t

Five new mexicanolide-type tetranortriterpenoids, tigloylseneganolide A (1), 2′R-methylbutanoylproceranolide (2), 2′S- methylbutanoylproceranolide (3), 2′R-cipadesin A (4), and 2′R-cipadesin (6), as well as the known 2′S-epimers of 4 and 6 (5 and 7), together with six other known limonoids, were isolated from the seeds of Cipadessa baccifera. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical methods. ¹H NMR-based conformational analysis was applied to establish the absolute configuration of the sterically hindered 2-methylbutanoyl in three epimeric pairs (2-7). A general rule for the determination of the absolute configurations of 2R- and 2S-methylbutanoyl groups at C-3 of a limonoid in a mixture is proposed.

Full text of DOI:10.1021/np070229t

1
344
J. Nat. Prod. 2007, 70, 1344-1347
Tetranortriterpenoids from Cipadessa baccifera
Li-She Gan, Xiao-Ning Wang, Yan Wu, and Jian-Min Yue*
State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People’s Republic of China
ReceiVed May 16, 2007
Five new mexicanolide-type tetranortriterpenoids, tigloylseneganolide A (1), 2′R-methylbutanoylproceranolide (2), 2′S-
methylbutanoylproceranolide (3), 2′R-cipadesin A (4), and 2′R-cipadesin (6), as well as the known 2′S-epimers of 4 and
6
(5 and 7), together with six other known limonoids, were isolated from the seeds of Cipadessa baccifera. The structures
1
of these compounds were elucidated on the basis of spectroscopic analyses and chemical methods. H NMR-based
conformational analysis was applied to establish the absolute configuration of the sterically hindered 2-methylbutanoyl
in three epimeric pairs (2-7). A general rule for the determination of the absolute configurations of 2R- and 2S-
methylbutanoyl groups at C-3 of a limonoid in a mixture is proposed.
-
Limonoids that have antifeedant, antimicrobial, or antimalarial
activities, isolated from the plants of the Meliaceae family, are of
interest to both phytochemists and agrochemists.1 Cipadessa
baccifera (Roth.) Miq. (Meliaceae) is a shrub and has been used
in folk medicine for the treatment of rheum, dysentery, and pruritus.3
Previous study on the seeds of C. baccifera reported three
carbonyl (1720 cm 1) and double-bond (1649 cm-1) groups. The
1
H NMR spectrum (Table 1) had three resonances at δ 7.50 (1H,
,2
dd, J ) 0.8, 0.7 Hz, H-21), 7.43 (1H, dd, J ) 1.6, 1.7 Hz, H-23),
and 6.48 (1H, dd, J ) 1.7, 0.7 Hz, H-22), typical of a â-substituted
furan ring; two olefinic proton resonances at δ 6.25 (1H, dd, J )
6.0, 2.8 Hz) and 6.16 (1H, s), typical of trisubstituted double bonds;
proton signals at δ 5.15 (1H, s) and 4.90 (1H, d, J = 9.1 Hz)
indicating two oxygenated methines; and resonances at δ 1.20, 1.04,
0.83, and 0.79 for four angular methyl groups. A tigloyl group was
also indicated by the proton signals at δ 7.00 (1H, qd, J ) 7.0, 1.4
4
tetranortriterpenoids and some other compounds. As part of our
continuing work on the chemical constituents of plants of the
5
Meliaceae family, five new mexicanolide-type tetranortriterpenoids,
tigloylseneganolide A (1), 2′R-methylbutanoylproceranolide (2), 2′S-
methylbutanoylproceranolide (3), 2′R-cipadesin A (4), and 2′R-
cipadesin (6), as well as the known 2S-epimers of 4 and 6 (5 and
Hz, H-3′), 1.92 (3H, s, H
Combined with the 13C NMR spectrum, the NMR data indicated
3
3
-4′), and 1.90 (3H, d, J ) 7.4 Hz, H -5′).
7
), together with six other known limonoids, have been isolated
that compound 1 was a mexicanolide-type tetranortriterpenoid with
a limonoid core, the same as that of seneganolide A. Comparison
6
from seeds of Cipadessa baccifera that were collected in Xishua-
ngbanna, China.
of the NMR and MS data of 1 with those of seneganolide A
indicated that compound 1 was its 3-O-tigloyl derivative. This was
confirmed by the HMBC spectrum, in which the tigloyl group was
connected to C-3 by the correlation between H-3 and C-1′. The
NOESY correlation between H-3 and H-2 indicated that the
O-tigloyl was â-oriented. The relative configuration of the limonoid
core in 1 was further confirmed by the NOESY spectrum. Therefore,
compound 1 was identified as tigloylseneganolide A.
Compound 2 showed a HREIMS molecular ion peak at m/z
5
5
54.2872 corresponding to the molecular formula C32
42 8
H O (calcd
-
1
54.2880). The strong and broad IR absorption band at 1732 cm
1
revealed the presence of carbonyl groups. The H NMR resonances
at δ 7.54 (H-21, d, J ) 0.7 Hz), 7.40 (H-23, dd, J ) 1.8, 1.5 Hz),
and 6.47 (H-22, d, J ) 1.2 Hz) were typical for a â-furan, and the
resonances at δ 1.14 (s), 1.05 (s), 0.81 (s), and 0.72 (s) were
assignable to four angular methyl groups. These data suggested
that compound 2 was likely to be a mexicanolide-type tetranor-
triterpenoid. The 13C NMR spectrum (with DEPT) confirmed the
above deduction and further indicated the presence of one ketone
group (δ 218.1), two esters (δ 174.1, C-7; 169.8, C-16), and one
double bond (δ 131.7, C-14; δ 127.7, C-8). A 2-methylbutyryloxy
3
group was identified by the proton resonances at δ 1.23 (H -4′, d,
1
J ) 6.9 Hz) and 0.90 (H -5′, t, J ) 7.4 Hz) in the H NMR and an
3
ester carbonyl at δ 176.3 in the 13C NMR. Detailed analysis of
spectroscopic data of 2 suggested that it was probably a 2-meth-
7
ylbutanoyl derivative of proceranolide. The HMBC experiment
Results and Discussion
confirmed the backbone of 2 and located the 2-methylbutanoyl at
C-3 by the correlation between H-3 and C-1′. Analysis of the
NOESY spectrum of 2, 2′R-methylbutanoylproceranolide, indicated
that the relative configuration of the limonoid skeleton was the same
as proceranolide.
Compound 1, a white powder, had the molecular formula
C
32
H
38 8
O as established on the basis of HREIMS at m/z 550.2569
+
[M] (calcd 550.2567). The IR spectrum showed the presence of
Compound 3 was isolated along with its 2′R-epimer (2) by
*
Corresponding author. Tel: 86-21-50806718. Fax: 86-21-50806718.
E-mail: jmyue@mail.shcnc.ac.cn.
semipreparative HPLC with a reversed-phased C8 silica gel
1
0.1021/np070229t CCC: $37.00
© 2007 American Chemical Society and American Society of Pharmacognosy
Published on Web 07/04/2007

Tetranortriterpenoids from Cipadessa baccifera
Journal of Natural Products, 2007, Vol. 70, No. 8 1345
Table 1. 1H NMR Data of Compounds 1-3 in CDCl
at 400 MHz.
3
1
2
3
2
3
5
6
9
1
3.72 (1H, m)
3.17 (1H, ddd, 9.8, 6.1, 2.0)
4.95 (1H, d, 10.1)
3.23 (1H, dd, 9.3, 3.3)
2.35 (2H, m)
2.04 (1H, br s)
1.79 (2H, m)
3.16 (1H, ddd, 9.8, 6.1, 2.0)
4.97 (1H, d, 10.0)
3.24 (1H, dd, 9.3, 3.6)
2.37 (2H, m)
2.05 (1H, br s)
1.79 (2H, m)
4.90 (1H, d, 9.2)
3.33 (1H, dd, 9.9, 2.2)
2.37 (2H, m)
2.25 (1H, m)
1
2
5
R 1.75 (1H, m)
â 1.49 (1H, m)
R 1.27 (1H, m)
â 1.95 (1H, m)
6.16 (1H, s)
1
1
R 1.09 (1H, m)
â 1.75 (1H, m)
R 3.45 (1H, dt, 20.9, 2.9)
â 3.74 (1H, d, 21.1)
5.64 (1H, s)
1.05 (3H, s)
1.14 (3H, s)
7.54 (1H, d, 0.7)
6.47 (1H, d, 1.2)
7.40 (1H, dd, 1.8, 1.5)
0.81 (3H, s)
R 1.10 (1H, m)
â 1.75 (1H, m)
R 3.44 (1H, dt, 20.6, 2.7)
â 3.77 (1H, d, 20.7)
5.67 (1H, s)
1.06 (3H, s)
1.15 (3H, s)
7.55 (1H, d, 0.7)
6.47 (1H, d, 1.2)
7.41 (1H, dd, 1.7, 1.7)
0.81 (3H, s)
1
1
1
2
2
2
2
2
3
7
8
9
1
2
3
8
9
0
5.15 (1H, s)
1.03 (3H, s)
1.20 (3H, s)
7.50 (1H, dd, 0.8, 0.7)
6.48 (1H, dd, 1.8, 0.7)
7.43 (1H, dd, 1.6,1.7)
0.82 (3H, s)
0.79 (3H, s)
6.25 (1H, dd, 6.0, 2.8)
0.72 (3H, s)
0.72 (3H, s)
R 2.12 (1H, dd, 16.1, 5.4)
â 2.77 (1H, dd, 14.9, 1.9)
3.70 (3H, s)
R 2.13 (1H, br d, 15.2)
â 2.78 (1H, dd, 15.5, 1.9)
3.70 (3H, s)
OMe
3.69 (3H, s)
2
3
′
′
2.46 (1H, m)
a 1.70 (1H, m)
2.43 (1H, m)
a 1.71 (1H, m)
7.00 (1H, q, 7.0, 1.4)
b 1.51 (1H, m)
1.23 (3H, d, 6.9)
0.90 (3H, t, 7.4)
b 1.50 (1H, m)
1.19 (3H, d, 7.3)
1.00 (3H, t, 7.3)
4
5
′
′
1.92 (3H, t, 1.2)
1.90 (3H, dd, 6.9, 1.2)
Table 2. 1H NMR Data of Compounds 4-7 in CDCl
at 400 MHz.
3
4
5
6 (7)
2
3
5
6
9
1
3.57 (1H, dd, 9.5, 2.5)
5.08 (1H, d, 9.7)
3.23 (1H, dd, 8.0, 2.8)
2.34 (2H, m)
3.56 (1H, dd, 9.5, 2.5)
5.08 (1H, d, 9.4)
3.22 (1H, dd, 7.9, 3.4)
2.34 (2H, m)
3.48 (1H, m)
4.81 (1H, d, 9.5)
3.41 (1H, m)
2.36 (2H, m)
1.92 (1H, m)
1.91 (1H, m)
2.23 (1H, br s)
a 2.08 (1H, m)
b 1.68 (1H, m)
a 1.66 (1H, m)
b 1.46 (1H, m)
2.19 (1H, br s)
a 2.89 (1H, dd, 18.7, 6.0)
b 2.81 (1H, br d, 18.8)
5.68 (1H, s)
1.08 (3H, s)
1.14 (3H, s)
7.78 (1H, s)
6.46 (1H, d, 0.7)
7.41 (1H, s)
1
2
R 1.78 (1H, m)
â 1.84 (1H, m)
R 1.18 (1H, m)
â 1.95 (1H, m)
1.57 (1H, m)
R 2.79 (1H, dd, 15.8, 4.7)
â 3.65 (1H, dd, 15.6, 14.7)
5.16 (1H, s)
1.00 (3H, s)
1.06 (3H, s)
7.47 (1H, d, 1.0)
6.45 (1H, dd, 1.1, 0.7)
7.42 (1H, dd, 2.0, 1.5)
0.80 (3H, s)
R 1.78 (1H, m)
â 1.83 (1H, m)
R 1.17 (1H, m)
â 1.95 (1H, m)
1.55 (1H, m)
R 2.79 (1H, dd, 15.7, 4.6)
â 3.66 (1H, dd, 15.4, 15.1)
5.15 (1H, s)
1.00 (3H, s)
1.06 (3H, s)
7.46 (1H, s)
6.44 (1H, d, 1.2)
7.42 (1H, dd, 1.7, 1.2)
0.80 (3H, s)
0.78 (3H, s)
3.31 (1H, d, 2.7)
3.72 (3H, s)
1
1
1
4
5
1
1
1
2
2
2
2
2
3
7
8
9
1
2
3
8
9
0
0.78 (3H, s)
0.82 (3H, s)
5.37 (1H, d, 6.3)
3.71 (3H, s)
0.79 (3H, s)
3.29 (1H, d, 2.5)
3.72 (3H, s)
OMe
2
3
′
′
2.59 (1H, m)
a 1.78 (1H, m)
b 1.55 (1H, m)
1.24 (3H, d, 7.0)
2.59 (1H, m)
2.44 (1H, m)
a 1.78 (1H, m)
b 1.54 (1H, m)
1.24 (3H, d, 7.1)
a 1.66 (1H, m)
b 1.44 (1H, m)
1.143 (3H, d, 5.6)
4
′
′
1
.136 (3H, d, 7.0)a
5
0.94 (3H, t, 7.6)
0.96 (3H, t, 7.4)
0.86 (3H, t, 7.4)
0
.92 (3H, t, 7.5)a
a
Chemical shifts of some protons of 7, where they are different from those of compound 6.
column. Its IR, UV, and MS spectra closely matched those of 2.
Compounds 4 and 5 were both obtained by semipreparative
1
1
13
Both compounds showed high similarity in the H NMR and
HPLC as white powders. The H NMR (Table 2) and C NMR
(Table 3) spectra of both compounds were similar to the formerly
13
C NMR spectra, with the main differences being the chemical
shifts of H -4′ and H -5′, suggesting that they were probably 2′-
8
3
3
isolated compound cipadesin A, in which the stereochemistry at
epimers. The NOESY spectrum showed that 3 shared the same
relative configurations as 2, except for C-2′ (see Supporting
Information). Finally, the structure of 3 was confirmed by prepara-
C-2′ was left unassigned. Analyses of the spectral data including
MS, IR, and 1D and 2D NMR (see Table 2, Table 3, and Supporting
Information) suggested that 4 and 5 were a pair of 2′-epimers of
cipadesin A. Comparison of the spectroscopic data of 4 and 5 with
those reported for cipadesin A revealed that 5, with a 2′S-
7
tion of 3 via esterification of proceranolide (recently isolated from
Swietenia mahagoni in our group) with (S)-2-methylbutyric acid.
Thus, compound 3 was assigned as 2′S-methylbutanoylprocerano-
lide.
configuraton, was identical to cipadesin A on the basis of their
very similar NMR data and optical rotations ([R]20
-114 (5); [R]
20
D
D

1
346 Journal of Natural Products, 2007, Vol. 70, No. 8
Gan et al.
Table 3. 13C NMR Data of Compounds 1-7 in CDCl
MHz.
at 100
3
1
2
3
4
5
6 (7)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
3
214.4
49.1
78.3
38.9
40.3
218.1
48.1
78.1
38.3
40.9
33.6
174.1
127.7
52.1
53.0
18.8
29.0
38.2
131.7
33.2
169.8
80.7
17.6
16.6
120.7
141.7
109.9
142.8
20.8
23.4
33.0
52.0
176.3
41.1
27.1
16.1
11.4
218.2
48.1
78.0
38.5
40.9
33.5
174.2
127.7
52.1
52.9
18.7
29.0
38.1
131.7
33.4
169.8
80.6
17.7
17.7
120.6
141.7
109.9
142.8
20.7
23.2
33.1
52.0
176.3
41.5
26.3
16.6
11. 7
214.2
48.8
76.8
39.2
42.5
33.1
174.2
60.6
55.9
48.2
19.3
33.4
36.4
45.9
34.0
172.0
78.9
26.4
15.9
120.1
141.0
110.3
143.1
20.9
22.6
63.3
52.3
175.7
41.2
26.9
16.7
11.6
214.3
48.8
76.8
39.4
42.5
33.1
174.2
60.6
55.9
48.2
19.3
33.4
36.4
45.9
34.1
172.0
78.8
26.5
15.8
120.1
140.9
110.3
143.1
20.9
22.4
63.5
52.3
175.8
41.5
26.6
17.4
11.9
217.1
48.8
76.9
38.5 (38.6)a
41.4
32.9
32.9
173.7
136.1
54.1
52.0
21.8
32.9
37.5
160.7
112.4
164.9
79.6
174.0
138.4
56.7
49.9
20.6
34.4
36.9
45.2
29.7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
8
9
0
169.3
76.9
21.8
22.2
15.6
15.7
120.2
141.4
110.2
143.1
21.0
22.5
129.2
52.0
166.8
128.2
139.3
12.2
120.7
141.9
109.7
142.9
22.5 (22.4)a
20.6
122.8
52.1
OMe
a
1
2
3
4
5
′
′
′
′
′
176.1 (176.0)
40.4 (40.8)a
a
Figure 1. Conformational analysis of the 2′R (2 and 4) and 2′S (3
and 5) methylbutanoyls in the compounds 2-5; “T” represent
NOESY correlations.
26.5 (26.3)
15.8 (16.2)a
11.3 (11.4)a
14.7
a
Chemical shifts of some carbons of 7, where they are different
from those of compound 6.
C-3 of a limonoid in a mixture was proposed. CH
deshielded in the case of 2′R than that having a 2′S-configuration
- δ (CH -4′) > 0: ∆δ2,3 ) δ - δ ) +13.9 Hz; ∆δ4,5
2.8 Hz; ∆δ6,7 ) +2.0 Hz), and CH -5′ was more shielded in the
case of 2′R than that having a 2′S-configuration (δ - δ (CH -5′)
) -40.3 Hz; ∆δ4,5 ) -10.0 Hz; ∆δ6,7
21.2 Hz) (Figure 1). Thus, compounds 6 and 7 in a mixture were
-4′ was more
3
(
+
δ
R
S
3
R
S
)
-
103 reported for cipadesin A). 2′R-Cipadesin A (4) was thus
identified as a new compound.
′R-Cipadesin and 2′S-cipadesin (6 and 7) were isolated in a
3
R
S
3
2
<
-
0: ∆δ2,3 ) δ
R
- δ
S
)
mixture by semipreparative HPLC (even under several optimized
HPLC conditions). H NMR (Table 2) analysis of the mixture of 6
and 7 showed that they were in a ratio of 3:5 as determined by the
values of the integral area on H
and 7 were overlapped except for those of H
H NMR spectrum. H NMR data showed that compound 7, with
a 2′S-configuration, was identical to cipadesin,5 as determined by
1
assigned as 2′R- and 2′S-cipadesin, respectively.
The six other nortriterpenoids were identified to be ruageanin
3
-5′. All the proton resonances of
-4′ and H -5′ in the
9
10
11
A , swietemahonolide, febrifugin, methyl 3â-isobutyryloxy-1-
6
3
3
12
13
oxomeliac-8,30-enate, khayasin T, and 3â-isobutyryloxymexi-
1
1
14
canolide using 1D NMR and MS data.
a
the closely related chemical shifts of H
6) was therefore identified as a new compound.
The stereochemistry at C-2′ for the three 2′-epimeric pairs was
assigned by detailed 1H NMR-based conformational analyses
Figure 1). The considerable steric interaction between the 2-me-
3
-4′ and H
3
-5′. 2′R-Cipadesin
Experimental Section
(
General Experimental Procedures. Optical rotations were mea-
sured on a Perkin-Elmer 341 polarimeter. UV spectra were measured
on a Shimadzu UV-2550 spectrophotometer. IR spectra were recorded
on a Perkin-Elmer 577 spectrometer with KBr disks. NMR spectra were
measured on a Bruker AM-400, Varian Inova-400, or Varian Inova-
600 spectrometer with TMS as internal standard. EIMS (70 eV) and
(
thylbutanoyl group and the limonoid core made one stable
1
conformation dominant in solution. Therefore, the H NMR of the
compounds with a 2′R- (in the cases of 2, 4, 6) and a 2′S-
methylbutanoyl group at C-3 (in the cases of 3, 5, 7) showed slight
differences in the acyl part. On biogenetic considerations, the
absolute configurations of the limonoid cores of compounds 1-7
are assumed as depicted, and the absolute configurations of C-2′
in the acyls of compounds 2-5 could be assigned from NOESY
spectra. Therefore, compound 2 was assigned to have a 2′R-
ESIMS were carried out on a Finnigan MAT95 mass spectrometer and
DECA
a Finnigan LC Q
instrument, respectively. All solvents were of
analytical grade (Shanghai Chemical Plant, Shanghai, People’s Republic
of China). Silica gel (200-300 mesh) was used for column chroma-
tography, and precoated silica gel GF254 plates (Qingdao Haiyang
Chemical Plant, Qingdao, People’s Republic of China) were used for
TLC. C18 reversed-phased silica gel (150-200 mesh, Merck), MCI gel
(CHP20P, 75-150 µm, Mitsubishi Chemical Industries Ltd.), and
configuration on the basis of NOESY correlations of H
-15 and H -5′/H -29, and compound 3 was assigned as having a
′S-configuration by the ROESY correlations of H -4′/H -29 and
H-2′/H -15, which is identical to the result determined by the
chemical method. The C-2′ absolute configurations of compounds
and 5 were assigned as 2′R- and 2′S-cipadesin A, respectively,
in a similar manner.
3
-4′, H-2′/
Sephadex LH-20 gel (Amersham Biosciences) were used for column
chromatography. Semipreparative HPLC was performed on a Waters
H
â
3
3
2
3
3
5
15 pump equipped with a Waters 2487 detector and a YMC-Pack
â
ODS-A column (250 × 10 mm, S-5 µm, 12 nm).
Plant Material. C. baccifera (Roth.) Miq. was collected in Xishua-
ngbanna, Yunnan Province, People’s Republic of China, and authen-
ticated by Professor You-Kai Xu of the Xishuangbanna Tropical
Botanical Garden (XTBG), Chinese Academy of Sciences. A voucher
specimen has been deposited in Shanghai Institute of Materia Medica,
Chinese Academy of Sciences (accession number: CBA-2006-2Y).
4
1
Furthermore, on the basis of the H NMR conformational analysis
Tables 1 and 2, Figure 1), a general rule for the determination of
(
the absolute configurations of 2R- and 2S-methylbutanoyl at the

Tetranortriterpenoids from Cipadessa baccifera
Journal of Natural Products, 2007, Vol. 70, No. 8 1347
+
Extraction and Isolation. Powdered air-dried seeds of C. baccifera
m/z 570 (38) [M] , 432 (20), 323 (40), 221 (100), 57 (48); HREIMS
(
4.9 kg) were extracted with 95% EtOH at room temperature to give
a crude extract (903 g), which was suspended in 1.5 L of H O and
extracted with petroleum ether (1000 mL × 3) and EtOAc (1000 mL
3), respectively. The EtOAc extract (60 g) was subjected to an MCI
gel column, eluted with H O/EtOH (1:0 to 0:1), to afford five fractions,
m/z 570.2832 (calcd for C32
2′S-Cipadesin A (5): white, amorphous solid; [R]
MeOH); UV (MeOH) λmax (log ꢀ) 200 (3.94), 206 (3.89) nm; IR (KBr)
42 9
H O , 570.2829).
20
2
D
-114 (c 0.07,
-
1
×
νmax 3437, 2974, 1736, 1458, 1263, 1186, 1148, 1024 cm ; EIMS m/z
+
2
570 (28) [M] , 432 (18), 323 (40), 221 (100), 57 (50).
CBE-1 to CBE-5. Fraction CBE-4 was subjected to a silica gel column
eluted with petroleum ether/EtOAc (6:1 to 0:1) to obtain two subfrac-
tions, E4a and E4b. E4a was separated by semipreparative HPLC with
a mobile phase of 80% acetonitrile in water to give 3â-isobutyry-
loxymexicanolide (6 mg), khayasin T (50 mg), 2′R-methylbutanoyl-
proceranolide (2, 25 mg), and 2′S-methylbutanoylproceranolide (3, 12
mg). E4b was separated into two subfractions by a silica gel column
Acknowledgment. Financial support from the Key Project of
National Foundation (Grant No. 30630072) and from the Shanghai
Municipal Scientific Foundation (Grant No. 06DZ22028) of the People's
Republic of China is gratefully acknowledged. We thank Associate
Professor You-Kai Xu for collection and identification of the plant
material.
3
eluted with petroleum ether/CHCl (1:1). The first subfraction, E4b1,
was purified by semipreparative HPLC with a mobile phase of 75%
acetonitrile in water to give tigloylseneganolide A (1, 5 mg), febrifugin
Supporting Information Available: 1H NMR spectra of the three
epimeric pairs 2-7; HMBC spectra of compounds 1, 2, and 5; NOESY
1
spectra of compunds 1, 2, 4, and 5; ROESY spectra of 3; enlarged H
(10 mg), and a mixture of 2′R-cipadesin (6) and 2′S-cipadesin (7) (11
NMR spectrum (δ 0.7-1.3 ppm) of 6 and 7 in a mixture. This material
is available free of charge via the Internet at http://pubs.acs.org.
mg) in the ratio of 3:5. The second fraction, E4b2, was separated on a
reversed-phased C-18 column eluted with 50% ethanol in water to give
ruageanin A (20 mg), methyl 3â-isobutyryloxy-1-oxomeliac-8,30-enate
References and Notes
(15 mg), and a mixed crystal, which was further purified by semi-
preparative HPLC with a mobile phase of 65% acetonitrile in water to
yield swietemahonolide (9 mg), 2′R-cipadesin A (4, 11 mg), and 2′S-
cipadesin A (5, 12 mg).
(1) (a) Taylor, D. A. H. In Progress in the Chemistry of Organic Natural
Products; Herz, W., Grisebach, H., Kirby, G. W., Eds.; Springer:
New York, 1984; Vol. 45, pp 1-102. (b) Mulholland, D. A.; Parel,
B.; Coombes, P. H. Curr. Org. Chem. 2000, 4, 1011-1054.
Tigloylseneganolide A (1): white, amorphous solid; [R]20
D
+268
(
2) (a) Champagne, D. E.; Koul, O.; Isman, M. B.; Scudder, G. G. E.;
Towers, G. H. N. Phytochemistry 1992, 31, 377-394. (b) Roy, A.;
Saraf, S. Biol. Pharm. Bull. 2006, 29, 191-201.
(
c 0.05, MeOH); UV (MeOH) λmax (log ꢀ) 211 (4.67), 282 (4.31) nm;
IR (KBr) νmax 3431, 2935, 1720, 1649, 1382, 1257, 1153, 1028, 873
-1
1
13
+
cm ; H NMR, Table 1; C NMR, Table 3; EIMS m/z 550 [M] (20),
(
3) An Editorial Committee of the Administration Bureau of Traditional
Chinese Medicine. Chinese Materia Medica (Zhonghua Bencao);
Shanghai Science & Technology Press: Shanghai, 1999; Vol. 5, 32.
38 8
397 (18), 83 (100), 55 (30); HREIMS m/z 550.2569 (calcd for C32H O ,
5
50.2567).
2
R]
′R-Methylbutanoylproceranolide (2): white, amorphous solid;
(4) (a) Luo, X. D.; Wu, S. H.; Ma, Y. B.; Wu, D. G. Phytochemistry
2000, 55, 867-872. (b) Luo, X. D.; Wu, S. H.; Ma, Y. B.; Wu, D.
G. Chin. Tradit. Herb. Drugs 2001, 32, 778-780.
2
0
[
(
1
D
-66 (c 0.09, MeOH); UV (MeOH) λmax (log ꢀ) 200 (3.95), 281
3.01) nm; IR (KBr) νmax 3435, 2970, 2937, 1732, 1460, 1382, 1256,
-1
1
13
(5) Wang, X. N.; Yin, S.; Fan, C. Q.; Wang, F. D.; Lin, L. P.; Ding, J.;
Yue, J. M. Org. Lett. 2006, 8, 3845-3848. (b) Yin, S.; Fan, C. Q.;
Wang, X. N.; Lin, L. P.; Ding, J.; Yue, J. M. Org. Lett. 2006, 8,
176, 1146, 1026 cm ; H NMR, Table 1; C NMR, Table 3; EIMS
+
m/z 554 (12) [M] , 458 (48), 430 (100), 328 (25), 210 (24), 85 (36),
7 (66); HREIMS m/z 554.2872 (calcd for C32 , 554.2880).
′S-Methylbutanoylproceranolide (3): white, amorphous solid;
5
42 8
H O
4
935-4938.
2
(
6) Abdelgaleil, S. A. M.; Iwagawa, T.; Doe, M.; Nakatani, M. Fitoterpia
2
0
[
(
1
R]
D
-85 (c 0.06, MeOH); UV (MeOH) λmax (log ꢀ) 200 (4.20), 281
2004, 75, 566-572.
(7) Sondengam, B. L.; Kamga, C. S.; Connolly, J. D. Phytochemistry
1980, 19, 2488.
(8) Leite, A. C.; Fernandes, J. B.; M. Fatima das G. F. da Silva; Vieira,
P. C. Z. Naturforsch. 2005, 60b, 351-355.
3.37) nm; IR (KBr) νmax 3439, 2928, 2852, 1732, 1462, 1381, 1257,
-1
1
13
178, 1147, 1026 cm ; H NMR, Table 1; C NMR, Table 3; EIMS
+
m/z 554 (12) [M] , 458 (48), 430 (96), 328 (28), 210 (28), 85 (50), 57
100).
Preparation of 3 from (S)-2-Methylbutyric Acid and Procera-
nolide. To a solution of CH Cl (3 mL) containing 5 mg of oxalyl
chloride and a catalytic amount of DMF was added 5 mg of (S)-2-
methylbutyric acid, and the mixture was stirred at room temperature.
(
(
9) Mootoo, B. S.; Ramsewak, R. J. Nat. Prod. 1996, 59, 544-547.
(
10) Kadota, S.; Marpaung, L.; Kikuchi, T.; Ekimoto, H. Chem. Pharm.
Bull. 1990, 38, 894-901.
11) Rao, M. M.; Krishna, E. M.; Gupta, P. S.; Singh, P. P. Ind. J. Chem.
2
2
(
1978, 16B, 823-825.
Then, 3 mg of proceranolide in 3 mL of CH
2
Cl
2
was added dropwise.
(12) Taylor, D. A. H. J. Chem. Soc. C 1969, 2439-2442.
(13) Kadota, S.; Marpaung, L.; Kikuchi, T.; Ekimoto, H. Chem. Pharm.
Bull. 1990, 38, 639-651.
The reaction mixture was stirred for 2 h at room temperature. After
workup, the resulting product was purified by semipreparative HPLC
to give compound 3a. Co-injection of 3a with 2, or 3a with 3, on HPLC
(
14) (a) Adesogan, E. K.; Bevan, C. W. L.; Powell, J. W.; Taylor, D. A.
H. Chem. Commun. 1966, 1, 27. (b) Adesogan, E. K.; Bevan, C. W.
L.; Powell, J. W.; Taylor, D. A. H. J. Chem. Soc. C 1966,
(
80% acetonitrile in water) and MS showed that 3a was identical to 3.
′R-Cipadesin A (4): white, amorphous solid; [R]2
0
-145 (c 0.08,
2
D
2127-2133.
MeOH); UV (MeOH) λmax (log ꢀ) 200 (3.93), 206 (3.93) nm; IR (KBr)
max 3435, 2972, 1732, 1460, 1382, 1261, 1180, 1146, 1026 cm ; EIMS
-1
ν
NP070229T