全 文 ： 药学学报 Acta Pharmaceutica Sinica 2013, 48 (8): 1281−1285 · 1281 ·




A new phenolic amide glycoside from Cimicifuga dahurica
ZHANG Fan1, HAN Li-feng1, PAN Gui-xiang1*, PENG Shuang1, ANDRE Ndagijimana1, 2
(1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine,
Tianjin 300193, China; 2. Institute of Scientific and Technological Research (IRST), Butare 227, Rwanda)
Abstract: A new phenolic amide glycoside, cimicifugamide A (1) along with four known compounds, trans-
feruloyl tyramine 4-O-β-D-glucopyranoside (2), (+)-isolariciresinol 3-O-β-D-glucopyranoside (3), cimidahurine (4),
and 24-epi-7, 8-didehydrocimigenol-3-O-β-D-xylopyranoside (5) were isolated from the rhizomes of Cimicifuga
dahurica. Compound 3 was identified as a lignan and has been obtained from Cimicifuga genus for the first
time. The structure of compound 1 was elucidated by IR, UV, HR-MS and NMR spectroscopic methods.
Key words: Cimicifuga dahurica; phenolic amide glycosides; lignan
CLC number: R284.1 Document code: A Article ID: 0513-4870 (2013) 08-1281-05
兴安升麻中一个新的酚类酰胺苷
张 帆 1, 韩立峰 1, 潘桂湘 1*, 彭 双 1, Andre Ndagijimana1, 2
(1. 天津中医药大学, 天津市现代中药重点实验室-省部共建国家重点实验室培育基地, 天津 300193;
2. 布塔雷科学技术研究院 (IRST), 卢旺达 布塔雷 227)

摘要: 从兴安升麻根茎中分离得到 1 个新化合物 cimicifugamide A (1) 和 4 个已知化合物 trans-feruloyl tyramine
4-O-β-D-glucopyranoside (2)、(+)-isolariciresinol 3-O-β-D-glucopyranoside (3)、cimidahurine (4) 和 24-epi-7, 8-
didehydrocimigenol-3-O-β-D-xylopyranoside (5)。化合物 3 为木脂素, 首次从升麻属中分离得到。通过 IR、UV、
HR-MS 及 NMR 等波谱方法对化合物 1 的结构进行了鉴定。
关键词: 兴安升麻; 酚类酰胺苷; 木脂素

The genus Cimicifuga, family Ranunculaceae,
comprises about 25 species distributed widely in Asia,
Europe and North America[1, 2]. C. dahurica, C. foetida,
C. heracleifolia, and C. simplex are the major Asian
Cimicifuga species. In the United States and the
European Union, C. racemosa, commonly known as
black cohosh, has been reported to reduce the frequency
and intensity of hot flashes and other menopause
symptoms[3, 4]. The rhizomes of C. dahurica as well

Received 2013-02-25; Accepted 2013-04-08.
Project supported by the National Natural Science Foundation of China
(81001633, 81173523) and the Program of Science and
Technology Department of Tianjin (11JCYBJC14800).
*Corresponding author Tel / Fax: 86-22-59596163,
E-mail: guixiangp@163.com
as other Cimicifuga species have been widely used in
various formulations of traditional Chinese medicine as
an antipyretic, antitoxic, antitumor, analgesic and anti-
inflammatory agents[5, 6].
Since 1959, chemical constituents of Cimicifuga
species have been extensively studied[7]. Previous
phytochemical studies have shown that Cimicifuga species
mainly contain constituents such as 9, 19-cycloartane
triterpenoid glycosides, cinnamic acid derivatives,
chromones and alkaloids[8]. Four phenolic amide
glycosides including cimicifugamide[9], isocimicifuga-
mide[10], trans-feruloyl-tyramine 4-O-β-D-glucopyranoside,
and trans-feruloyl-(3-O-methyl)dopamine 4-O-β-D-glu
copyranoside[11] have been isolated from Asian
Cimicifuga species. One lignan, namely actaealactone,
· 1282 · 药学学报 Acta Pharmaceutica Sinica 2013, 48 (8): 1281−1285

was isolated from C. racemosa[12].
In the present study, the chemical constituents of
the rhizomes of C. dahurica were investigated. Here
we describe in detail the application of NMR and
HR-TOF-MS to structural elucidation of a new phenolic
amide glycoside, namely cimicifugamide A (1) (Figure
1), together with the isolation and structural elucidation
of four known compounds (2−5)[10, 11, 13, 14]. Compound
3 was identified as a lignan and has been obtained from
Cimicifuga genus for the first time.


Figure 1 The structures of compounds 1−2

Results and discussion
The 1H NMR spectrum of compound 1 revealed
the presence of two 1, 3, 4-trisubstituted aromatic rings
at δ 6.67 (1H, d, J = 2.0 Hz, H-2 ), 6.50 (1H, dd, J = 8.0,
2.0 Hz, H-6 ), 6.69 (1H, d, J = 8.0 Hz, H-5 ) and 7.16
(1H, d, J = 1.5 Hz, H-2), 7.11 (1H, dd, J = 8.0, 1.5 Hz,
H-6), 7.16 (1H, d, J = 8.0 Hz, H-5); a pair of trans-
olefinic protons at δ 6.47 (1H, d, J = 15.5 Hz, H-8)
and 7.44 (1H, d, J = 15.5 Hz, H-7) and one methoxyl
protons at δ 3.87 (3H, s). It was also observed a
β-D-galactopyranosyl moiety at δ 5.29 (1H, d, J = 8.0
Hz, Gal-1 ), 3.64 (1H, dd, J = 8.0, 3.0 Hz, Gal-2 ), 4.10
(1H, dd, J = 3.0, 3.0 Hz, Gal-3 ), 3.60 (1H, dd, J = 9.5,
3.0 Hz, Gal-4 ), 3.83 (1H, m, Gal-5 ), 3.83 (1H, m,
Gal-6 ), and 3.68 (1H, dd, J = 12.0, 5.5 Hz, Gal-6 )[15].
The 1H-1H correlation spectroscopy (COSY) spectrum
displayed a connectivity between δH 2.70 (H-7 ) and
3.44 (H-8 ). The long-range correlations between H-8
at δ 3.44 and C-9 at δC 168.8 in HMBC spectrum
was also observed. The above data were very similar
to those obtained for compound 2. The fact that C-8
and C-9 were linked by a nitrogen atom was clearly
confirmed by the NMR spectra in DMSO-d6, the proton
signal at δH 8.07 (1H, t, J = 5.7 Hz) showed long-
range correlations with C-9. The 13C NMR spectrum
displayed 6 carbon signals at δC 100.3, 72.0, 72.9, 68.6,
75.9 and 62.8 which could be attributed to β-D-galactose
moiety according to literature[10]. In the HMBC spectrum,
long-range correlations were showed from H-1 to
C-4, and the methoxyl group signal at δH 3.87 to
C-3 separately, suggesting that the sugar was located at
C-4 while the methoxyl group was located at C-3 (Fig-
ure 2).


Figure 2 Key HMBC correlations of compound 1

From all of the above evidence, compound 1 was
determined as (2E)-3-[4-(β-D-galactopyranosyloxy)-
3-methoxyphenyl]-N-[2-(3-hydroxy-4-hydroxyphenyl)
ethyl]-2-propenamide or cimicifugamide A. The 1H
and 13C NMR spectral data of compound 1 were shown
in Table 1.

Table 1 1H and 13C NMR spectral data of compound 1
Position δH (J in Hz) HMBC δC
1 130.9
2 7.16 (d, 1.5) 4, 6, 7 112.3
3 150.9
4 149.7
5 7.16 (d, 8.0) 1, 3 117.3
6 7.11 (dd, 8.0, 1.5) 2, 4, 7 122.7
7 7.44 (d, 15.5) 2, 6, 9 141.3
8 6.47 (d, 15.5) 1, 9 120.4
9 168.8
1 132.0
2 6.67 (d, 2.0) 4, 6, 7 116.9
3 146.2
4 144.8
5 6.69 (d, 8.0) 1, 3 116.4
6 6.50 (dd, 8.0, 2.0) 2, 4, 7 121.0
7 2.70 (t, 7.5) 1, 2, 6, 8 36.0
8 3.44 (t, 7.5) 9, 1, 7 42.5
-OCH3 3.87 (s) 3 56.8
Gal-1 5.29 (d, 8.0) 4 100.3
2 3.64 (dd, 8.0, 3.0) 1 72.0
3 4.10 (dd, 3.0, 3.0) 1, 2, 5 72.9
4 3.60 (dd, 9.5, 3.0) 5, 6 68.6
5 3.83 (m) 4, 6 75.9
6 3.83 (1H, m) 4 62.8
3.68 (1H, dd, 12.0, 5.5)
ZHANG Fan, et al: A new phenolic amide glycoside from Cimicifuga dahurica · 1283 ·

Experimental
General experimental procedures UV data
were determined on a PuXi TU-1901 spectrophotometer.
The NMR spectra data were recorded on a Bruker
AVANCE III 500 spectrometer using tetramethylsilane
as an internal standard. The chemical shift values
were reported in unit (δ) and coupling constants (J)
were given in Hz. HR-TOF-MS spectrometric data
were obtained with an Agilent 6520 Q-TOF mass
spectrometer (Agilent Corp, Santa Clara, CA, USA).
HPLC grade methanol and acetonitrile were used.
Deionized water was purified using a Milli-Q system
(Millipore, Bedford, MA, USA). All other chemicals
used were of analytical grade.
Plant material The rhizomes of C. dahurica were
purchased from An Guo herb market (Hebei province,
China) in September 2011. The plant material was
identified by Prof. Li Tian-xiang from Tianjin University
of Traditional Chinese Medicine.
Extraction and isolation The dried and crushed
rhizomes of C. dahurica (5 kg) were soaked and
extracted three times with 70% EtOH aqueous solution
at room temperature. The combined EtOH extract
was concentrated under reduced pressure until the
ethanol content was totally eliminated. The resulting
aqueous fraction was then partitioned successively with
petroleum ether, EtOAc and n-BuOH.
The n-BuOH partition (200 g) was subjected to
a silica gel column chromatography and eluted with
CHCl3−MeOH (20∶3 → 0∶1) to yield eight fractions
(namely A−H). Fraction D (15 g) was subjected to
ODS column chromatography eluted with 15% CH3CN
and 20% CH3CN to give fraction D1 and D2 respectively.
Fraction D1 was further purified on preparative HPLC
(3% CH3CN, Agilent Eclipse XDB-C18, 250 mm ×
21.2 mm, 7 μm, America, Agilent Corporation) to
afford compound 3 (7 mg). Fraction D2 was further
separated by preparative HPLC (15% CH3CN) to obtain
compounds 1 (33 mg), 2 (36 mg) and 4 (22 mg).
The EtOAc partition (100 g) was chromatographed
over a silica gel column eluted with CHCl3−MeOH−
H2O (50∶3∶1 → 35∶3∶1) to give six (a−f) fractions.
Fraction b (2.3 g) was further separated by a silica
gel column which was eluted with petroleum ether−
EtOAc (4∶1 → 1∶6) to afford four fractions (b1−
b4). Fraction b2 (300 mg) was further separated by
preparative HPLC (80% MeOH) to achieve compound
5 (55 mg).
Structure elucidation
Compound 1 Yellow amorphous powder; [α] 25D
−12.9 (c 015, MeOH); IR (KBr) νmax: 3 366, 2 935,
1 656, 1 510, 1 259, 1 074 cm−1; UV (MeOH) λmax (log ε):
230 (3.14), 290 (3.03), 313 (2.97) nm; 1H and 13C NMR
spectral data see Table 1. HR-ESI-MS (negative) m/z:
490.170 7 [M−H]− (calcd. for C24H28NO10, 490.171 9).
Acid hydrolysis of compound 1 Compound 1
(3.0 mg) was dissolved in 1 mol·L−1 HCl (30 mL) and
refluxed at 80 ℃ for 3 h. The reaction solution was
cooled at room temperature, neutralized with 1 mol·L−1
NaOH and then extracted with EtOAc. The NaOH layer
concentrated to give the sugar fraction. The residue
was analyzed by TLC with EtOAc−MeOH−H2O−HOAc
(13∶4∶1∶3). The obtained Rf = 0.35 value was in
accordance with authentic sample D-galactose.
Compound 2 Yellow amorphous powder; [α] 25D
−268.2 (c 0.1, MeOH); IR (KBr) νmax: 3 364, 2 945,
2 833, 1 032 cm−1; UV (MeOH) λmax: 230, 283, 312 nm.
ESI-MS (negative) m/z: 474.1 [M−H]−; δ 7.44 (1H, d,
J = 15.5 Hz, H-7), 7.18 (1H, d, J = 2.0 Hz, H-2), 7.16
(1H, d, J = 8.0 Hz, H-5), 7.11 (1H, dd, J = 8.0, 2.0 Hz,
H-6), 7.05 (2H, d, J = 8.5 Hz, H-2, 6 ), 6.71 (2H, d,
J = 8.5 Hz, H-3, 5 ), 6.47 (1H, d, J = 15.5 Hz, H-8),
4.90 (1H, d, J = 8.0 Hz, Glu-1 ), 3.89 (3H, s, OCH3).
The 13C NMR spectral data see Table 2. The data
were consistent with trans-feruloyl tyramine 4-O-β-D-
glucopyranoside in the literature[11].
Compound 3 White amorphous powder; [α] 25D
+7.5 (c 0.16, MeOH); UV (MeOH) λmax: 233, 283 nm.
ESI-MS (negative) m/z: 521.1 [M−H]−; δ 6.74 (1H,
d, J = 8.0 Hz, H-5 ), 6.69 (1H, d, J = 2.0 Hz, H-2 ),
6.65 (1H, s, H-8), 6.64 (1H, dd, J = 8.0, 2.0 Hz, H-6 ),
6.19 (1H, s, H-5), 4.04 (1H, d, J = 7.6 Hz, Glu-1 ), 3.81
(3H, s, OCH3), 3.78 (3H, s, OCH3). The 13C NMR
spectral data see Table 2. The data were consistent
with (+)-isolariciresinol 3-O-β-D-glucopyranoside in
the literature[13].
Compound 4 White amorphous powder; [α] 17D
−51.4 (c 0.15, MeOH); IR (KBr) νmax: 3 680, 1 600,
1 656, 1 515 cm−1. ESI-MS (negative) m/z: 315.1
[M−H]−; δ 6.74 (1H, d, J = 8.0 Hz, H-5 ), 6.69 (1H,
d, J = 2.0 Hz, H-2 ), 6.64 (1H, dd, J = 8.0, 2.0 Hz,
H-6 ), 5.29 (1H, d, J = 8.0 Hz, Gal-1 ). The 13C NMR
spectral data see Table 2. The data were consistent
with cimidahurine in the literature[10].
Compound 5 White amorphous powder; [α] 25D
−9.6 (c 0.35, CHCl3); IR (KBr) νmax: 3 420, 1 630 cm−1.
· 1284 · 药学学报 Acta Pharmaceutica Sinica 2013, 48 (8): 1281−1285

Table 2 13C NMR spectral data of compounds 2, 3 and 4
Position 2 3 4
1 131.2 33.9 132.0
2 112.4 39.5 119.4
2a 65.2
3 151.0 45.9 146.6
3a 69.5
4 149.5 47.9 146.6
5 117.6 117.4 116.8
6 122.7 145.1 125.0
7 141.5 147.1 39.5
8 120.5 112.4 64.3
9 168.8 129.1
10 134.4
1 131.3 138.7
2 130.7 114.3
3 116.3 148.9
4 157.0 145.8
5 116.3 116.1
6 130.7 123.1
7 35.8
8 42.5
-OCH3 3-56.8 7-56.4
3-56.5
Glc/Gal-1 102.3 105.2 102.1
2 74.8 75.2 72.1
3 77.9 77.9 72.8
4 71.3 71.7 68.5
5 78.3 78.1 75.8
6 62.5 62.8 62.7

Table 3 13C NMR spectral data of compound 5 in C5D5N
Position 13C NMR Position 13C NMR
1 30.3 19 28.3
2 29.5 20 23.4
3 88.3 21 19.6
4 40.4 22 29.5
5 42.7 23 73.8
6 21.7 24 84.0
7 114.2 25 68.6
8 148.1 26 30.7
9 21.2 27 25.8
10 28.2 28 18.5
11 25.5 29 25.9
12 33.9 30 14.3
13 41.1 Xyl-1 107.4
14 50.8 2 75.5
15 79.7 3 78.5
16 112.4 4 71.2
17 60.6 5 67.0
18 21.6
ESI-MS (positive) m/z: 619.3 [M+H]+; δ 4.79 (1H,
d, J = 7.3 Hz, Xyl-1 ), 1.16, 1.41, 1.31, 1.27, 1.28,
1.05 (18H, s, 6×CH3), 1.05 (1H, d, J = 4.0 Hz, H-19),
0.51 (1H, d, J = 4.0 Hz, H-19). The 13C NMR spectral
data see Table 3. The data were consistent with 24-
epi-7, 8-didehydrocimigenol-3-O-β-D-xylopyranoside
in the literature[14].
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