Four novel furanocoumarin glucosides, candinosides A, B, C and D, from Heracleum candicans Wall

Article abstract of DOI:10.1007/s11418-010-0470-1

Four novel furanocoumarin glucosides, candinosides A, B, C and D (1-4), were isolated from the roots of Heracleum candicans Wall. Their structures were established using chemical and spectral methods.

Full text of DOI:10.1007/s11418-010-0470-1

J Nat Med (2011) 65:116–121
DOI 10.1007/s11418-010-0470-1
ORIGINAL PAPER
Four novel furanocoumarin glucosides, candinosides A, B, C
and D, from Heracleum candicans Wall
•
Atsuko Inoue Makio Shibano
•
•
•
Masahiko Taniguchi Kimiye Baba
Nian-He Wang
Received: 9 June 2010 / Accepted: 23 August 2010 / Published online: 2 October 2010
Ó The Japanese Society of Pharmacognosy and Springer 2010
Abstract Four novel furanocoumarin glucosides, candi-
nosides A, B, C and D (1–4), were isolated from the roots
of Heracleum candicans Wall. Their structures were
established using chemical and spectral methods.
report deals with the isolation and structural elucidation of
the four new natural products.
Results and discussion
Keywords Heracleum candicans ꢀ Umbelliferae ꢀ
The acetone extract of the roots of this plant yielded four
new coumarins (1–4) after chromatographic purification.
Candinoside A (1) was obtained as a pale yellow viscous
Furanocoumarin glucoside
25
oil, ½aꢁD ?7.5° (c 0.578, pyridine), which presented a
Introduction
fluorescent yellowish-green spot on TLC under UV light
(365 nm). The UV spectrum showed absorption maxima at
298.0, 248.0 and 210.5 nm and IR spectrum absorption
bands at 3414, 2979, 1718, 1623, 1588, 1468, 1442, 1403,
1334, 1294, 1154 and 1089 cm-1, indicating the presence
of linear-type furanocoumarins. The molecular formula
was determined as C38H40O16 on the basis of high-reso-
lution (HR) positive FAB-MS (m/z: 775.2211, [M ? Na]?,
calcd. 775.2214).
The 1H-NMR spectrum of 1 showed the presence of two
heraclenol units [heraclenol unit I: dH 7.76 (1H, d,
J = 9.7 Hz), 7.70 (1H, d, J = 2.3 Hz), 7.36 (1H, s), 6.81
(1H, d, J = 2.3 Hz), 6.35 (1H, d, J = 9.7 Hz), 4.65 (1H,
dd, J = 10.4, 2.5 Hz), 4.46 (1H, dd, J = 10.4, 8.0 Hz),
4.10 (1H, dd, J = 8.0, 2.5 Hz), 1.40 (3H, s), 1.34 (3H, s)],
[heraclenol unit II: dH 7.78 (1H, d, J = 9.6 Hz), 7.71 (1H,
d, J = 2.3 Hz), 7.38 (1H, s), 6.81 (1H, d, J = 2.3 Hz), 6.36
(1H, d, J = 9.6 Hz), 4.69 (1H, dd, J = 10.0, 2.6 Hz), 4.54
(1H, dd, J = 10.0, 8.8 Hz), 4.00 (1H, dd, J = 8.8, 2.6 Hz),
1.47 (3H, s), 1.34 (3H, s)] and one glucopyranose unit [dH
4.66 (1H, d, J = 8.0 Hz), 3.29 (1H, dd, J = 9.0, 8.0 Hz),
3.71 (1H, t, J = 9.0 Hz), 3.51 (1H, t, J = 9.0 Hz), 3.39
(1H, ddd, J = 9.0, 5.3, 3.5 Hz), 3.89 (1H, dd, J = 11.8,
3.5 Hz), 3.79 (1H, dd, J = 11.8, 5.3 Hz)] (Table 1). Each
unit was also identified by 13C-NMR spectroscopy (Table 2).
The roots of Heracleum candicans Wall are used in
Chinese folk medicine as an antipyretic and diaphoretic
agent in local areas of Yunnan Province, PR China [1]. In
our previous studies, we reported the isolation and struc-
tural elucidation of 14 coumarin derivatives, in addition to
two known polyacetylenes, two known phenylpropanoids
and 25 known coumarins, including heraclenol and
marmesin [2–4]. However, the chemical constituents of
this plant have not yet been investigated thoroughly. In the
course of our studies on the coumarin components of this
plant, we investigated the constituents of the high-polarity
fractions and isolated four novel furanocoumarin gluco-
sides, candinosides A–D (1–4), as shown in Fig. 1. This
A. Inoue ꢀ M. Shibano ꢀ M. Taniguchi ꢀ K. Baba (&)
Osaka University of Pharmaceutical Sciences,
4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
e-mail: baba@gly.oups.ac.jp
N.-H. Wang
Institute of Botany, Jiangsu Province and Academia Sinica,
Nanjing 20014, China
123

J Nat Med (2011) 65:116–121
117
OH
6"
O
5"
14
13
O
4"
O
O
HO
14'
O
O
O
2"
OH
HO
1"
OH
3"
OH
15
12
13'
12'
15'
11
O
HO
O
11'
O
HO
O
8
8'
2
8a
O
7
O
O
7'
O
8'a
O
2'
3'
O
OH
O
O
OH
9
9'
4a
3
6
10
6'
4'a
4
5
candinoside A (1)
candinoside B (2)
10'
5'
4'
O
O
O
OH
OH
O
6"'
HO
HO
O
5"'
4"'
O
HO
6'
14"
13"
O
O
O
2"'
HO
12"
1"'
3'
OH
HO
3"'
2'
4'
5'
6
15"
2"
5
O
O
11"
4a
4
O
O
7
8"
8"a
O
O
7"
6"
O
O
O
3
O
O
8
8a
9"
O
2
O
4"a
3"
10"
O
5"
4"
candinoside C (3)
candinoside D (4)
Fig. 1 Structures of 1–4
Table 1 1H-NMR spectral data for 1, 2 and heraclenol in CDCl3
1
2
Heraclenol
3/30
4/40
5/50
6.35d (9.7)
7.76d (9.7)
7.36s
6.36d (9.6)
7.78d (9.6)
7.38s
6.33d (9.6)
7.74d (9.6)
7.34s
6.36d (9.7)
7.76d (9.7)
7.35s
6.37d (9.6)
7.76d (9.6)
7.39s
9/90
10/100
11/110
7.70d (2.3)
6.81d (2.3)
4.46dd (10.4, 8.0)
4.65dd (10.4, 2.5)
4.10dd (8.0, 2.5)
1.34s
7.71d (2.3)
6.81d (2.3)
4.54dd (10.0, 8.8)
4.69dd (10.0, 2.6)
4.00dd (8.8, 2.6)
1.34s
7.70d (2.2)
6.79d (2.2)
7.72d (2.3)
6.80d (2.3)
4.59dd (10.1, 8.4)
4.66dd (10.1, 3.1)
3.91dd (8.4, 3.1)
1.27s
7.70d (2.3)
6.83d (2.3)
4.45dd (10.1, 7.6)
4.66dd (10.1, 3.0)
4.10dd (7.6, 3.0)
1.34s
4.42dd (10.2, 7.9)
4.75dd (10.2, 2.7)
12/120
14/140
15/150
12-OH
13-OH
100
3.89ddd (7.9, 4.1, 2.7)
1.31s
1.40s
1.47s
1.38s
1.44s
1.34s
3.54d (4.1)
2.74s
4.66d (8.0)
4.66d (8.0)
200
300
3.29dd (9.0, 8.0)
3.71t (9.0)
3.44dd (8.7, 8.0)
3.65t (8.7)
400
3.51t (9.0)
3.70t (8.7)
500
600
3.39ddd (9.0, 5.3, 3.5)
3.89dd (11.8, 3.5)
3.79dd (11.8, 5.3)
3.29ddd (8.7, 5.5, 2.6)
3.83dd (11.8, 2.6)
3.70dd (11.8, 5.5)
Chemical shifts are in d values and are followed by multiplicities and J values (in Hz)
In the heteronuclear multiple bond correlation (HMBC)
spectrum of 1, the anomeric proton signal of dH 4.66 (H-100,
glucopyranose unit) was correlated with the carbon signal
of dc 78.9 (C-13, heraclenol unit I), and dH 1.34 (H-14,
heraclenol unit I) and dH 1.40 (H-15, heraclenol unit I) with
dc 97.1 (C-100, glucopyranose unit); dH 3.71 (H-300, gluco-
pyranose unit) with dc 77.9 (C-130, heraclenol unit II)
(Fig. 2). Thus, 1 was assumed to be a furanocoumarin
glucoside composed of two heraclenol units and a gluco-
pyranose unit, and the two heraclenol units were found to be
located at the C-100 and C-300 positions in the glucopyranose
unit. The structure has an ether bond at C-300 of the gluco-
pyranose unit and a novel glycosidic bond. Previously, the
absolute configuration of the C-12 position of heraclenol
123

118
J Nat Med (2011) 65:116–121
Table 2 13C-NMR spectral data for 1, 2 and heraclenol in CDCl3
of candinoside A (1) was found to be that shown in Fig. 1.
This structure was supported by analyses of the 1H-1H
COSY, HMQC, HMBC and NOESY spectra of 1.
1
2
Heraclenol
2/20
3/30
4/40
4a/4a0
5/50
6/60
7/70
8/80
8a/8a0
9/90
10/100
11/110
12/120
13/130
14/140
15/150
100
160.6
114.5
144.5
116.4
113.6
126.0
148.1a
131.68b
143.34
146.85
106.76c
75.1
160.9
114.4
144.8
116.4
113.7
126.1
148.2a
131.71b
143.28
146.94
106.78c
75.1
160.6
114.5
144.5
116.4
113.49d
126.07e
148.0f
131.79g
143.24
146.86
106.72h
75.1
160.9
114.4
144.7
116.4
113.51d
126.15e
148.1f
131.74g
143.20
146.93
106.75h
75.0
160.1
114.7
144.3
116.4
113.7
126.0
147.9
131.5
143.2
146.8
106.8
75.7
Candinoside B (2) was obtained as a pale yellow viscous
oil, [a]2D5 ?30.8° (c 0.857, pyridine), which presented a
fluorescent yellowish-green spot on TLC under UV light
(365 nm). The UV spectrum showed absorption maxima at
298.0, 248.0 and 210.5 nm and IR spectrum absorption
bands at 3424, 2979, 1717, 1623, 1588, 1468, 1442, 1403,
1334, 1294, 1153 and 1095 cm-1, indicating the presence
of linear-type furanocoumarins. The molecular formula
was found to be C38H40O16 on the basis of HR positive
FAB-MS (m/z: 775.2217, [M ? Na]?, calcd. 775.2214).
1
The H-NMR and 13C-NMR spectral data (Tables 1, 2)
were very similar to those of 2, showing the presence of
two heraclenol units and one glucopyranose unit.
75.4
77.1
75.4
77.4
76.0
Upon analyzing the HMBC spectral data, three-bond
correlations were observed between the anomeric proton
signal of dH 4.66 (H-1000, glucopyranose unit) and the car-
bon signal of dc 78.9 (C-13, heraclenol unit I), and dH 1.34
(H-14, heraclenol unit I) and dH 1.38 (H-15, heraclenol unit
I) and dc 96.6 (C-100, glucopyranose unit); dH 3.70 (H-400,
glucopyranose unit) and dc 78.5 (C-130, heraclenol unit II).
On the basis of this evidence, the structure of candinoside
B (2) was elucidated as shown in Fig. 1.
78.9
77.9
78.9
78.5
71.5
23.6
25.0
23.3
22.92i
26.5
22.86i
25.0
22.8
24.0
26.6
97.1
96.6
200
73.8
74.1
300
78.0
77.0
400
71.2
71.3
500
75.6
76.1
600
62.9
62.0
Candinoside C (3) was obtained as a pale yellow viscous
25
Chemical shifts are in d values
a–i
Assignment may be reversed
oil, ½aꢁD ?76.9° (c 0.172, pyridine), which presented a
fluorescent yellowish-green spot on TLC under UV light
(365 nm). The UV spectrum showed absorption maxima at
300.0, 249.0 and 210.5 nm and IR spectrum absorption
OH
bands at 3424, 2901, 1719, 1627, 1400 and 1105 cm-1
,
O
indicating the presence of linear-type furanocoumarins.
The molecular formula was found to be C36H38O14 on the
basis of HR positive FAB-MS (m/z: 717.2150, [M ? Na]?,
calcd. 717.2159).
HO
O
O
OH
HO
OH
O
O
The 1H-NMR spectrum (Table 3) of 3 showed the
presence of one heraclenol unit, [dH 7.82 (1H, d,
J = 9.6 Hz), 7.71 (1H, d, J = 2.2 Hz), 7.42 (1H, s), 6.84
(1H, d, J = 2.2 Hz), 6.39 (1H, d, J = 9.6 Hz), 4.67 (1H,
dd, J = 10.2, 2.7 Hz), 4.58 (1H, dd, J = 10.0, 8.9 Hz),
3.97 (1H, dd, J = 8.9, 2.7 Hz), 1.49 (3H, s), 1.31 (3H, s)],
one marmesin unit [dH 7.58 (1H, d, J = 9.4 Hz), 7.20 (1H,
s), 6.74 (1H, s), 6.21 (1H, d, J = 9.4 Hz), 4.81 (1H, dd,
J = 9.4, 8.2 Hz), 3.22 (2H, m), 1.35 (6H, s)] and one
glucopyranose unit [dH 4.59 (1H, d, J = 8.0 Hz), 3.22 (1H,
dd, J = 9.2, 8.0 Hz), 3.70 (1H, t, J = 9.2 Hz), 3.53 (1H, t,
J = 9.2 Hz), 3.30 (1H, ddd, J = 9.2, 4.9, 3.8 Hz), 3.70
(1H, br.d), 3.62 (1H, br.d)]. Upon analyzing the HMBC
spectral data, three-bond correlations were observed
between the anomeric proton signal of dH 4.59 (H-1000,
glucopyranose unit) and the carbon signal of dc 78.6 (C-40,
marmesin unit), and dH 3.70 (H-3000, glucopyranose unit)
and dc 77.8 (C-1300, heraclenol unit) (Fig. 2). Moreover, the
O
O
O
O
O
O
1
OH
O
HO
O
O
HO
O
OH
O
O
O
O
3
O
O
Fig. 2 Main HMBC correlations of 1 and 3
was found to be R using the modified Mosher’s method [5].
Although we made no attempt to determine it directly, the
configuration of the C-12 and C-120 positions of 1 was also
assumed to be R, similar to heraclenol. Thus, the structure
123

J Nat Med (2011) 65:116–121
119
Table 3 1H-NMR spectral data of 3, 4 and marmesin in CDCl3
3
4
Marmesin
3
6.21d (9.4)
7.58d (9.4)
7.20s
300
400
500
900
1000
1100
6.39d (9.6)
7.82d (9.6)
7.42s
3
6.20d (9.5)
7.58d (9.5)
7.20s
300
400
500
900
1000
1100
6.37d (9.6)
7.79d (9.6)
7.40s
3
6.21d (9.4)
4
4
4
7.60d (9.4)
7.22s
5
5
5
8
6.74s
7.71d (2.2)
6.84d (2.2)
4.58dd (10.0, 8.9)
4.67dd (10.0, 2.7)
3.97dd (8.9, 2.7)
1.31s
8
6.71s
7.71d (2.3)
6.83d (2.3)
4.33dd (10.1, 7.7)
4.68dd (10.0, 2.9)
4.11dd (7.7, 2.9)
1.32s
8
6.74s
20
30
50
60
4.81dd (9.4, 8.2)
3.22m
20
30
50
60
4.86t (8.9)
3.23d (8.9)
1.32s
20
30
50
60
4.74dd (9.2, 8.6)
3.22m
1.35s
1.24s
1200
1400
1500
1.34s
1200
1400
1500
1.38s
1.49s
1.39s
1000
2000
3000
4000
5000
6000
4.59d (8.0)
3.22dd (9.2, 8.0)
3.70t (9.2)
4.59d (7.3)
3.59dd (7.3, 9.2)
3.59t (9.2)
3.53t (9.2)
3.54t (9.2)
3.30ddd (9.2, 4.9, 3.8)
3.62brd
3.31ddd (9.2, 4.5, 4.2)
3.64m
3.70brd
Chemical shifts are in d values and are followed by multiplicities and J values (in Hz)
Table 4 13C-NMR spectral data of 3, 4 and marmesin in CDCl3
this evidence, the structure of candinoside B (2) was elu-
cidated as shown in Fig. 1.
3
4
Marmesin
Candinoside D (4) was obtained as a pale yellow viscous
25
2
3
4
161.4 200
112.3 300
143.6 400
161.0
114.4
144.9
2
3
4
161.4 200
112.3 300
143.1 400
160.6
114.6
144.7
2
3
4
161.4
112.2
143.7
oil, ½aꢁD -42.0° (c 0.339, pyridine), which presented a
fluorescent yellowish-green spot on TLC under UV light
(365 nm). The UV spectrum showed absorption maxima at
334.0sh, 300.0, 249.0 and 210.5 nm and IR spectrum
absorption bands at 3420, 2894, 1719, 1626, 1588, 1400
and 1099 cm-1, indicating the presence of linear-type
furanocoumarins. The molecular formula was found to be
C36H38O14 on the basis of HR positive FAB-MS (m/z:
717.2161, [M ? Na]?, calcd. 717.2159).
4a 112.7 4a00
116.5 4a 112.7 4a00
116.4 4a 112.7
5
6
7
8
123.2 500
124.8 600
163.3 700
98.0 800
113.9
126.2
148.4
131.8
5
6
7
8
123.3 500
124.7 600
163.3 700
97.9 800
113.9
126.2
148.1
131.5
5
6
7
8
123.4
125.0
163.1
97.9
8a 155.7 8a00
143.5 8a 155.7 8a00
147.0 20 89.8 900
29.9 1000 106.9 30 30.2 1000 106.9 30
143.4 8a 155.6
146.9 20
20
30
40
50
60
90.0 900
91.1
29.5
71.6
26.1
24.2
1
The H-NMR and 13C-NMR spectral data (Tables 3, 4)
were very similar to those of 3, showing the presence of
one heraclenol unit, one marmesin unit and one gluco-
pyranose unit. Long-range correlations were observed
between the anomeric proton signal of dH 4.59 (H-1000,
glucopyranose unit) and the carbon signal of dc 78.9 (C-40,
marmesin unit), and dH 3.59 (H-2000, glucopyranose unit)
and dc 78.4 (C-1300, heraclenol unit). Thus, the structure
was formulated as 4 in Fig. 1.
78.6 1100
22.6 1200
22.5 1300
1400
75.1 40
77.0 50
77.8 60
25.7
78.9 1100
22.1 1200
22.4 1300
1400
75.5 40
77.7 50
78.4 60
26.2
1500
23.7
1500
20.9
1000
2000
3000
4000
5000
6000
97.6
97.4
73.7
74.7
These four new furanocoumarin glucosides, candino-
sides A–D (1–4), have interesting structures, with an ether
bond at C-200 or C-300 or C-400 of the glucopyranose unit to
connect with an aglycone, except for the C-100 O-glycosidic
bond. To the best of our knowledge, these novel glucosides
are the first reported from natural products. Moreover,
since the ether bonds at C-200, C-300 or C-400 of the four new
glycosides are as difficult to hydrolyze as C-glucoside,
their biological activity must be interesting.
77.5
77.2
71.1
71.4
75.5
75.0
62.7
62.7
Chemical shifts are in d values
acid hydrolysis of 3 gave marmesin, and the optical rota-
tion [a]2D5 was ?9.58° [6]. It was concluded that the agly-
cone was not nodakenetin but marmesin. On the basis of
123

120
J Nat Med (2011) 65:116–121
Experiments
General
55% MeOH; flow rate: 2 mL/min; detection: UV 254 nm)
to give candinoside A (1) (24.8 mg) and candinoside B (2)
(16.0 mg). Fraction H was rechromatographed on silica
gel with Sephadex LH-20 (MeOH) followed by ODS
(80% MeOH) and PTLCs (CH2Cl2:MeOH = 6:1 and
EtOAc:MeOH = 8:1) to give candinoside C (3) (5.1 mg)
and candinoside D (4) (3.6 mg).
lH- and 13C-NMR, COSY, DEPT, HMQC, HMBC and
NOESY spectra were recorded on a Varian Unity INOVA-
500 spectrometer (Palo Alto, CA, USA), operating at
500 MHz for proton and 125 MHz for carbon, with tetra-
methylsilane (TMS) as an internal standard. HR-FAB-MS
spectra were obtained using a JEOL MS700V mass spec-
trometer (Tokyo, Japan). UV and IR spectra were recorded
on a Shimadzu UVmini-1240 (Kyoto, Japan) and a JASCO
FT/IR-680 Plus spectrophotometer (Osaka, Japan),
respectively. ORD spectra were recorded on a JASCO J820
digital polarimeter. Column chromatography was per-
formed using PSQ100B silica gel (Fuji Silycia, Aichi,
Japan), YMC GEL ODS-A 60-400/230 (Kyoto, Japan) and
Sephadex LH-20 (GE Healthcare Japan, Tokyo, Japan).
HPLC was performed using Shimadzu LC-10AT, SPD-
10A and SCL-10A LC instruments. TLC and preparative
TLC were carried out on Merck silica gel F254 plates
(Darmstadt, Germany) and Whatmann silica gel 150A PLK
5F (Maidstone, UK), respectively. Spots and bands were
detected by UV irradiation (254 and 365 nm).
Candinoside A (1)
Yellowish viscous oil, HR-FAB-MS (positive mode) m/z:
775.2211 [M ? Na]? (calcd. for C38H40O16Na: 775.2214),
FAB-MS m/z (rel. int.): 775 [M ? Na]? (9), 753 (3), 449
25
(22), 287 (100), 269 (32), 202 (56). ½aꢁD ?7.5° (c 0.578,
pyridine). IR (KBr) cm-1: 3414, 2979, 1718, 1623, 1588,
1468, 1442, 1403, 1334, 1294, 1154, 1089, 1034. UVkmax
(MeOH:dioxane = 1:1) nm (log e): 298.0 (4.12), 248.0
1
(4.42), 210.5 (4.53). H- and 13C-NMR data are shown in
Tables 1 and 2.
Candinoside B (2)
Yellowish viscous oil, HR-FAB-MS (positive mode) m/z:
775.2217 [M ? Na]? (calcd. for C38H40O16Na: 775.2214),
FAB-MS m/z (rel. int.): 775 [M ? Na]? (69), 753 (2), 449
Plant material
25
(24), 287 (100), 269 (32), 202 (58). ½aꢁD ?30.8° (c 0.857,
pyridine). IR (KBr) cm-1: 3424, 2979, 1717, 1623, 1588,
1468, 1442, 1403, 1334, 1294, 1153, 1095. UVkmax
(MeOH:dioxane = 1:1) nm (log e): 298.0 (4.43), 248.0
Air-dried roots of H. candicans were collected from plants
grown in Lijiang, Yunnan Province, PR China, in
September 2004. A voucher specimen was deposited at the
Institute of Botany, Jiangsu Province, and Academia
Sinica, Nanjing, PR China. The plant was identified by one
of the authors (N.W.).
1
(4.72), 210.5 (4.82). H- and 13C-NMR data are shown in
Tables 1 and 2.
Candinoside C (3)
Extraction and isolation
Yellowish viscous oil, HR-FAB-MS (positive mode) m/z:
717.2150 [M ? Na]? (calcd. for C36H38O14Na: 717.2159),
FAB-MS m/z (rel. int.): 717 [M ? Na]? (2), 449 (1), 287
The roots (3.5 kg) were chopped into small pieces and
extracted with acetone (10 L 9 4) at room temperature.
The combined acetone extracts were concentrated to
dryness in vacuo. The residue (300.2 g) was subjected to
column chromatography on silica gel (2.8 kg) using a gra-
dient of mixtures of hexane–EtOAc (2:1 ? 1:2), CH2Cl2–
MeOH (10:1 ? 5:1) and MeOH to furnish 11 fractions (fr.)
[fr. 1 (5.0 g), fr. 2 (2.3 g), fr. 3 (8.6 g), fr. 4 (47.4 g), fr. 5
(8.9 g), fr. 6 (24.0 g), fr. 7 (3.9 g), fr. 8 (14.9 g), fr. 9
(16.7 g), fr. 10 (48.4 g) and fr. 11 (96.9 g)].
25
(4), 221 (14), 147 (34). ½aꢁD ?76.9° (c 0.172, pyridine). IR
(KBr) cm-1: 3424, 2901, 1719, 1627, 1400, 1105. UVkmax
(MeOH:dioxane = 1:1) nm (log e): 300.0 (4.21), 249.0
1
(4.46), 210.5 (4.60). H- and 13C-NMR data are shown in
Tables 3 and 4.
Acid hydrolysis of 3
Fraction 9 was rechromatographed on silica gel and ODS
(80% MeOH) to give heraclenol (7.1 g) and marmesin
(0.34 g). Fraction 10 was rechromatographed on silica gel
(CH2Cl2–MeOH = 20:1 ? 1:1) to furnish 8 fractions (fr.
A–fr. H). Fraction F was rechromatographed on Sephadex
LH-20 (MeOH) followed by preparative HPLC (column:
Nucleosil 5C18 AB, 10 mm i.d. 9 250 mm; mobile phase:
3 (3.1 mg) was dissolved in 3.0% HCl:MeOH = 1:1
(5 mL) and heated in a water bath at 85°C for 2 h. The
reaction mixture was diluted with water and then extracted
with EtOAc. The EtOAc layer was chromatographed
on PTLC (CH2Cl2:MeOH = 30:1) to give marmesin
25
(1.1 mg). The optical rotation was ½aꢁD ? 9.58° (c 0.110,
123

J Nat Med (2011) 65:116–121
121
1
CHCl3). The H- and 13C-NMR data (Tables 3, 4) were
2. Doi M, Nakamori T, Shibano M, Taniguchi M, Wang N-H, Baba
K (2004) Candibirin A, a furanocoumarin dimmer isolated from
Heracleum candicans Wall. Acta Crystallogr C60:o833–o835
3. Nakamori T, Taniguchi M, Shibano M, Wang N-H, Baba K (2008)
Chemical studies on the root of Heracleum candicans Wall. J Nat
Med 62:403–412
identical to those reported in the literature [7].
Candinoside D (4)
4. Inoue A, Taniguchi M, Shibano M, Wang N-H, Baba K (2010)
Chemical studies on the root of Heracleum candicans Wall. J Nat
Med 64:175–181
5. Niu X-M, Li S-H, Wu L-X, Li L, Gao L-H, Sun H-D (2004) Two
new coumarin derivatives from the roots of Heracleum rapula.
Planta Med 70:578–581
Yellowish viscous oil, HR-FAB-MS (positive mode) m/z:
717.2161 [M ? Na]? (calcd. for C36H38O14Na: 717.2159),
FAB-MS m/z (rel. int.): 717 [M ? Na]? (4), 449 (15), 287
25
(41), 269 (22), 203 (56), 124 (100). ½aꢁD -42.0° (c 0.339,
pyridine). IR (KBr) cm-1: 3420, 2894, 1719, 1626, 1588,
1400, 1099. UVkmax (MeOH:dioxane = 1:1) nm (log e):
334.0sh (4.08), 300.0 (4.12), 249.0 (4.32), 210.5 (4.52).
1H- and 13C-NMR data are shown in Tables 3 and 4.
6. Ross SA, Sultana GNN, Burandt CL, ElSohly MA, Marais JPJ,
Ferreira
D
(2004) Syncarpamide,
a
new antiplasmodial
(?)-norepinephrine derivative from Zanthoxylum syncarpum.
J Nat Prod 67:88–90
7. Elgamal MHA, Elewa NH, Elkhrisy EAM, Duddeck H (1979)
Carbon-13 nuclear magnetic resonance spectra. Part XI. Carbon-13
NMR chemical shifts and carbon–proton coupling constants of
some furocoumarins and furochromones. Phytochemistry
18:139–143
Acknowledgments The authors are grateful to Dr. K. Minoura for
NMR spectral recordings and to Mrs. M. Fujitake for mass spectral
recordings at the Osaka University of Pharmaceutical Sciences. This
work was partially supported by the NSFC (project 30270097), PR
China.
References
1. Zhonghuabencao Editorial Board (1999) Zhonghuabencao, vol 5.
Shanghai Scientific and Technological Press, Shanghai, p 958 (in
Chinese)
123