Two new lignan glycosides from the seeds of Cuscuta chinensis

Article abstract of DOI:10.1080/10286020.2010.506434

Two new lignan glycosides, 2'-hydroxyl asarinin 2'-O-β-D- glucopyranoside (cuscutoside C, 1) and 2'-hydroxyl asarinin 2'-O-β-D- apiofuranosyl-(1→2)-[-D-glucopyranosyl-(1→6)]-D-glucopyranoside (cuscutoside D, 2), were isolated from the seeds of Cuscuta chinensis Lam., along with six known compounds, 2'-hydroxyl asarinin 2'-O-β-D- glucopyranosyl-(1→6)-D-glucopyranoside (3), 2'-hydroxyl asarinin 2'-O-β-D-apiofuranosyl-(1→2)-D-glucopyranoside (cuscutoside A, 4), kaempferol 3,7-di-O-β-D-glucopyranoside (5), 5-caffeoyl quinic acid (6), 4-caffeoyl quinic acid (7), and cinnamic acid (8). Their structures were elucidated on the basis of spectroscopic analyses including HR-ESI-MS, ESI-MS/MS, 1H and ¹³C NMR, HSQC, HMBC, and TOCSY.

Full text of DOI:10.1080/10286020.2010.506434

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Two new lignan glycosides from the
seeds of Cuscuta chinensis
a
a
a
a
Xiang-Hui He , Wen-Zhi Yang , A-Hui Meng , Wen-Ni He , De-
a
a
An Guo & Min Ye
a
The State Key Laboratory of Natural and Biomimetic Drugs,
School of Pharmaceutical Sciences, Peking University, Beijing,
100191, China
Published online: 08 Nov 2010.
To cite this article: Xiang-Hui He , Wen-Zhi Yang , A-Hui Meng , Wen-Ni He , De-An Guo & Min Ye
(2010): Two new lignan glycosides from the seeds of Cuscuta chinensis , Journal of Asian Natural
Products Research, 12:11, 934-939
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Journal of Asian Natural Products Research
Vol. 12, No. 11, November 2010, 934–939
Two new lignan glycosides from the seeds of Cuscuta chinensis
Xiang-Hui He, Wen-Zhi Yang, A-Hui Meng, Wen-Ni He, De-An Guo and Min Ye*
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences,
Peking University, Beijing 100191, China
(
Received 23 April 2010; final version received 1 July 2010)
0
0
Two new lignan glycosides, 2 -hydroxyl asarinin 2 -O-b-D-glucopyranoside (cuscuto-
0
0
side C, 1) and 2 -hydroxyl asarinin 2 -O-b-D-apiofuranosyl-(1 ! 2)-[b-D-glucopyr-
anosyl-(1 ! 6)]-b-D-glucopyranoside (cuscutoside D, 2), were isolated from the seeds
0
0
of Cuscuta chinensis Lam., along with six known compounds, 2 -hydroxyl asarinin 2 -
0
0
O-b-D-glucopyranosyl-(1 ! 6)-b-D-glucopyranoside (3), 2 -hydroxyl asarinin 2 -O-b-
D-apiofuranosyl-(1 ! 2)-b-D-glucopyranoside (cuscutoside A, 4), kaempferol 3,7-di-
O-b-D-glucopyranoside (5), 5-caffeoyl quinic acid (6), 4-caffeoyl quinic acid (7), and
cinnamic acid (8). Their structures were elucidated on the basis of spectroscopic
analyses including HR-ESI-MS, ESI-MS/MS, H and C NMR, HSQC, HMBC, and
TOCSY.
1
13
Keywords: Cuscuta chinensis Lam.; lignan; cuscutoside C; cuscutoside D
1
.
Introduction
order to find out the relationship between
bioactivities and chemical constituents, we
conducted the phytochemical studies on
the seeds of C. chinensis, particularly
aiming to obtain new bioactive lignans. As
a result, two new furofuran-type lignan
glycosides, cuscutoside C (1) and cuscuto-
side D (2) (Figure 1), were isolated from
an ethanol extract, together with two
TuSiZi, which is derived from the seeds of
Cuscuta chinensis Lam., is a commonly
used traditional Chinese medicine (TCM).
It was first recorded in the ancient Chinese
herbal classic ShenNong’s Herbal around
2
000 years ago. TuSiZi was used as a tonic
by TCM practitioners for the treatment of
deficiency in kidney and liver. Modern
researches have shown that it can improve
sexual function, prevent and treat cardio-
vascular diseases, regulate the body’s
immune system, treat osteoporosis, and
prevent senescence [1–9]. All these
activities were hitherto considered to be
due to flavonoids [10]. Recently, our
phytochemical screening of C. chinensis
by liquid chromatography coupled with
mass spectrometry discovered a series of
lignans and quinic acid derivatives [11].
Although a number of lignans had been
isolated from this plant [12–14], many
compounds remain to be unknown. In
0
0
known lignans (2 -hydroxyl asarinin 2 -
O-b-D-glucopyranosyl-(1 ! 6)-b-D-glu-
0
copyranoside (3) [13] and 2 -hydroxyl
0
asarinin 2 -O-b-D-apiofuranosyl-(1 ! 2)-
b-D-glucopyranoside or cuscutoside A (4)
[12]), one flavonoid (kaempferol 3,7-di-O-
b-D-glucopyranoside (5) [15]), two quinic
acid derivatives (5-caffeoyl quinic acid (6)
and 4-caffeoyl quinic acid (7) [16]), and
one phenolic acid (cinnamic acid, 8) [17].
Among them, 5, 6, 7, and 8 were reported
from this plant for the first time. The
structures of 1 and 2 were elucidated on the
basis of spectroscopic analyses including
*Corresponding author. Email: yemin@bjmu.edu.cn
ISSN 1028-6020 print/ISSN 1477-2213 online
q 2010 Taylor & Francis
DOI: 10.1080/10286020.2010.506434
http://www.informaworld.com

Journal of Asian Natural Products Research
935
Figure 1. Structures of cuscutoside C (1) and D (2).
1
13
C
HR-ESI-MS, ESI-MS/MS, H and
NMR, HSQC, HMBC, and TOCSY.
spectrum also showed signals due to
0
2 -hydroxyl asarinin (Table 1). In addition,
signals (dC 60.8, 69.9, 76.7, 77.1, 73.4,
101.9) due to a hexosyl residue were
2
.
Results and discussion
observed. By comparing with reported
NMR spectral data [12] and by acid
hydrolysis–TLC analysis, the hexose was
identified as glucose. The coupling con-
stant of the anomeric proton at dH 4.71
Compound 1 was obtained as a white
amorphous powder. The HR-ESI-MS
þ
spectrum showed the [M þ Na] ion at
m/z 555.1481, thus its molecular formula
was established as C H O . In the
2
6 28 12
(
d, J ¼ 7.3 Hz) revealed that the glucosyl
negative ESI-MS/MS spectrum, the
[
residue should be oriented in the b-
configuration. The location of the sugar
2
M 2 H] ion at m/z 531 yielded a product
ion at m/z 369 by losing 162 Da, suggesting
that compound 1 contained one hexosyl
1
residue. The H NMR spectrum showed
0
moiety was deduced to be at C-2 (d
148.8), according to the HMBC correlation
C
0
0
0
between H-1 (d 4.71) of Glc and C-2 of
H
signals due to five aromatic protons in the
region of d 6.81–6.91, signals due to four
methylenedioxy protons in the region of dH
the aglycone (Figure 2). Based on the
H
above analyses, the structure of 1 was
0
0
elucidated as 2 -hydroxyl asarinin 2 -O-b-
D-glucopyranoside, and was named cuscu-
toside C.
5
.90–6.10, and signals due to protons of
ditetrahydrofurofuran (dH 2.87 (m), 3.81
dd, J ¼ 3.4, 9.0 Hz), 4.01 (dd, J ¼ 4.0,
(
Compound 2 was obtained as a white
amorphous powder. Based on the HR-ESI-
MS data, its molecular formula was
9
.1 Hz), 4.14 (dd, J ¼ 6.4, 6.6 Hz), 4.57 (d,
J ¼ 5.2 Hz), 5.08 (d, J ¼ 4.2 Hz)). These
0
signals were very similar to those of 2 -
hydroxyl asarinin-type furofuran lignans
1
13
deduced as C H O . The H and
37 46 21
C
0
NMR spectral data indicated that 2
0
[12,13]. Indeed, several 2 -hydroxyl asar-
inin glycosides had been reported from the
seeds of C. chinensis [12,13]. Thus, the
aglycone of compound 1 was deduced to be
possessed the same 2 -hydroxyl asarinin
aglycone as 1. The only difference was the
sugar moiety. In the negative ESI-MS/MS
2
spectrum, an [M 2 H] ion at m/z 825 and
0
13
2
-hydroxyl asarinin. The
C NMR

9
36
X.-H. He et al.
Figure 2. Key HMBC correlations of cuscutoside C (1) and D (2).
2
fragment ions [M 2 H 2 hexose] at m/z
0
0
elucidated as 2 -hydroxyl asarinin 2 -O-b-
D-apiofuranosyl-(1 ! 2)-[b-D-glucopyra-
nosyl-(1 ! 6)]-b-D-glucopyranoside, and
was named cuscutoside D.
2
63, [M 2 H 2 hexose 2 pentose] at
6
m/z 531, and [M 2 H 2 2hexose 2
2
pentose] at m/z 369 were observed. It
suggested that the sugar moiety of 2 should
contain two hexosyl residues and one
pentosyl residue. The exact sugar types
and sequence were determined by detailed
analyses of the 1D and 2D NMR spectra.
Comparison of the carbon chemical shifts
The structures of known compounds
–8 were identified by comparing with the
3
literature data.
3. Experimental
3
.1 General experimental procedures
1
3
with reported C NMR spectral data
12,13] and TLC analysis after acid
The optical rotations were measured on a
Rudolph Research Analytical Autopol III
automatic polarimeter. Melting point were
measured with an uncorrected X-4A
microscope melting point apparatus
[
hydrolysis allowed the identification of
sugar types as Glc and Api. Proton signals
due to the sugar residues were assigned
according to HSQC and TOCSY spectra
(
CBIO Bioscience & Technologies Co.
(
correlations between H-1 (d 5.00) and
Table 1). In the HMBC spectrum,
Ltd, Beijing, China). UV spectra were
recorded on a TU1901 UV–vis spectro-
photometer (Beijing Purkinje General
Instrument Co. Ltd, Beijing, China). IR
spectra were recorded on a Nicolet
NEXUS-470 spectrometer (Madison, WI,
USA). 1D and 2D NMR spectra were
obtained on a Bruker Avance III 400
spectrometer. HR-ESI-MS spectra were
obtained on a Bruker Apex IV FT-MS
spectrometer (Billerica, MA, USA). ESI-
MS/MS spectra were recorded on a
Finnigan LCQ Advantage ion trap mass
0
0
H
000
0
C-2 (d 148.1), between H-1 (d 4.15)
C
H
0
0
0000
and C-6 (d 69.0), and between H-1 (dH
C
00
5
.35) and C-2 (dC 78.8) indicated the
attachment positions of sugars to sugars
and sugars to the aglycone (Figure 2).
0
0
From the J values of H-1 (d 5.00, d,
H
J ¼ 8.0 Hz), H-10
00
(dH 4.15, d,
0000
J ¼ 8.0 Hz), and H-1 (dH 5.35, d,
J ¼ 4.0 Hz), the b-configurations of Glc
and Api were suggested [18]. From the
above evidences, the structure of 2 was

Journal of Asian Natural Products Research
937
1 13
Table 1. H (400 MHz) and C NMR (100 MHz) spectral data for compounds 1 and 2 (in DMSO-
d , d in ppm, J in Hz).
6
1
2
d
H
d
C
d
H
d
C
Aglycone
C(1)
CH(2)
C(3)
C(4)
CH(5)
CH(6)
CH(7)
CH(8)
135.5
135.5
106.5
146.5
146.5
107.9
119.3
84.6
6.91 (s)
106.5 6.92 (s)
146.5
147.4
107.9 6.86 (d, J ¼ 8.0)
119.3 6.83 (d, J ¼ 8.0)
84.3 4.54 (d, J ¼ 4.0)
54.0 2.86 (m)
70.8 4.12 (m) (Ha)
3.80 (m) (He)
124.5
148.8
98.4 6.92 (s)
146.4
141.7
6.85 (overlapped)
6.84 (overlapped)
4.57 (d, J ¼ 5.2)
2.87 (m)
54.1
70.7
CH
2
(9)
4.14 (dd, J ¼ 6.6, 6.4) (Ha)
3.81 (dd, J ¼ 9.0, 3.4) (He)
0
C(1 )
123.7
148.1
97.7
146.5
141.5
104.6
80.5
0
CH(3 )
C(2 )
0
6.84 (s)
0
C(4 )
0
CH(6 )
C(5 )
0
0
6.81 (s)
5.08 (d, J ¼ 4.2)
104.6 6.78 (s)
81.1 5.05 (d, J ¼ 4.0)
54.0 2.86 (m)
72.4 4.19 (m) (Ha)
3.95 (m) (He)
CH(7 )
0
CH (9 )
CH(8 )
0
2.87 (m)
4.14 (dd, J ¼ 6.6, 6.4) (Ha)
54.0
72.5
2
4.01 (dd, J ¼ 9.1, 4.0) (He)
OZCH
2
ZO 5.99 (s), 5.95 (d, J ¼ 11.4)
100.8 5.94 (d, J ¼ 8.0), 5.99 (s)
100.8
100.9
1
01.0
0
CH(1 )
2
-O-Glc
0
0
0
4.71 (d, J ¼ 7.3)
3.21 (m)
3.29 (m)
3.14 (m)
3.21 (m)
101.9 5.00 (d, J ¼ 8.0)
73.4 3.47 (m)
77.1 3.01 (m)
69.9 3.17 (m)
76.7 3.68 (m)
98.4
78.8
77.0
70.1
75.1
69.0
0
CH(2 )
0
0
CH(3 )
0
0
CH(4 )
0
0
CH(5 )
0
0
CH
2
(6 )
0
-O-Glc
3.43 (m), 3.72 (d, J ¼ 11.3)
60.8 3.60 (d, J ¼ 4.0), 3.94 (d, J ¼ 4.0)
0
6
0
00
CH(1 )
4.15 (d, J ¼ 8.0)
2.95 (m)
3.79 (m)
3.02 (m)
3.10 (m)
103.5
73.5
76.7
70.1
76.9
61.1
0
00
CH(2 )
0
00
CH(3 )
0
00
CH(4 )
0
CH (6 )
00
CH(5 )
00
0
3.64 (d, J ¼ 8.0), 3.40 (m)
2
0
CH(1 )
0
-O-Api
2
0
000
5.35 (d, J ¼ 4.0)
3.80 (m)
3.47 (m)
109.2
76.2
78.0
63.4
73.5
0
000
CH(2 )
0
(4 )
000
CH(3 )
0
000
000
CH
2
3.31 (d, J ¼ 8.0)
0
CH (5 )
2
3.57 (m), 3.86 (m)
spectrometer (ThermoFinnigan, San Jose,
CA, USA). Semi-preparative HPLC was
conducted on a LabAlliance Series 1500
pump equipped with a LabAlliance Model
500 variable wavelength detector and an
Agilent Zorbax SB-C18 semi-preparative
column (9.4 £ 250 mm, 5 mm). Sephadex
LH-20 (GE Healthcare Bio-Sciences

9
38
X.-H. He et al.
Corporation, formerly Amersham Pharma-
cia Biotechnology Incorporation, NJ,
USA), polyamide (80–100 mesh; Linjiang
Reagent Chemical Corporation, Jiangsu,
China), and ODS (YMC Company, Ltd,
Kyoto, Japan) were used for column
chromatography (CC). TLC were per-
formed on silica gel plates (Branch of
Qingdao Haiyang Chemical Plant,
Qingdao, China) and polyamide sheets
subjected to semi-preparative HPLC and
eluted with aqueous acetonitrile (10%, v/v,
2 ml/min) to afford 6 (6 mg) and 7 (20 mg).
Fr.5 (12 g) was also subjected to ODS CC
(eluted with gradient aqueous methanol,
10% ! 100%, v/v) to give six fractions
(Fr.5.1–5.6). Fr.5.6 was then applied to
semi-preparative HPLC and eluted with
aqueous acetonitrile (33%, v/v, 2 ml/min)
to give 1 (60 mg) and 8 (5 mg).
(Taizhou Si-Jia Biochemical Plastic Com-
pany, Zhejiang, China) with spots exam-
ined in the UV light at 254 nm.
3
.3.1 Cuscutoside C (1)
White amorphous powder. mp 112–
2
0
D
1
138C. ½aꢀ 273.5 (c ¼ 0.067, MeOH).
UV (MeOH) l (nm): 291.0, 237.0. IR
max
3
.2 Plant material
2
KBr) nmax (cm ): 3383, 2883, 1630,
1
(
The seeds of C. Chinensis Lam. were
collected in Beijing in fall 2000 and were
identified by Dr Min Ye. A voucher
specimen (No. 20000901) has been depos-
ited at the Pharmacognosy Biotechnology
Laboratory, School of Pharmaceutical
Sciences, Peking University, China.
1
1
503, 1485, 1440, 1400, 1347, 1249, 1180,
1
074, 1036, 931, 864, 810, 717, 559. H
1
3
and C NMR spectral data: see Table 1.
þ
HR-ESI-MS: m/z 555.1481 [M þ Na]
(calcd for C H O Na, 555.1473).
26 28 12
3
.3.2 Cuscutoside D (2)
White amorphous powder. mp 153–
20
3
.3 Extraction and isolation
1
UV (MeOH) l
548C. ½aꢀ 299.0 (c ¼ 0.067, MeOH).
D
Air-dried seeds of C. Chinensis (5 kg)
were pulverized and sieved (40 mesh),
defatted with petroleum ether under reflux,
and then extracted with 95% ethanol under
reflux for three times (2 h for each time).
The extract was concentrated in a rotary
vacuum evaporator to give 600 g of crude
residue. The residue was dispersed in hot
(nm): 291.5, 237.0. IR
max
2
1
(KBr) nmax (cm ): 3394, 2884, 1705,
1632, 1503, 1485, 1440, 1249, 1179, 1068,
13
1
1037, 931, 875, 813, 717, 560. H and
C
NMR spectral data: see Table 1. HR-ESI-
þ
MS: m/z 849.2417 [M þ Na] (calcd for
C H O Na, 849.2424).
37 46 21
water and then extracted with CHCl . The
3
3
.4 Acid hydrolysis of 1 and 2
water layer afforded 500 g of the residue
which was subjected to a polyamide
column and eluted with aqueous ethanol
Compounds 1 (3 mg) and 2 (5 mg) were
heated in 2 ml of 2 M CF COOH at 908C
3
(
(
0% ! 40%, v/v) to give eight fractions
for 12 h, respectively. The reaction mix-
ture was then diluted with 2 ml H O and
Fr.1–8). Fr.7 (7.5 g) was subjected to an
2
ODS CC (eluted with gradient aqueous
methanol, 10% ! 100%, v/v) and yielded
extracted with CHCl3 (4 ml £ 3). The
water layer was evaporated to dryness
and then dissolved with 1 ml of MeOH.
The solutions were then subjected to silica
gel TLC together with authentic D-Glc and
D-Api samples, and developed using n-
BuOH–Me CO–H O (4:5:1) as the
1
0 fractions (Fr.7.1–7.10). Fr.7.8 was then
subjected to semi-preparative HPLC and
eluted with aqueous methanol (45%, v/v,
2
ml/min) to afford 2 (35 mg), 3 (140 mg),
and 4 (36 mg). Fr.7.5 was subjected to
Sephadex LH-20 CC and eluted with
methanol to afford 5 (30 mg). Fr.7.2 was
2
2
solvent. The Rf values of D-Glc and
D-Api were 0.63 and 0.80, respectively.

Journal of Asian Natural Products Research
939
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Acknowledgement
We are grateful for the financial support from
the Peking University Health Science Center
11] M. Ye, Y.N. Yan, and D.A. Guo,
Rapid Commun. Mass Spectrom. 19,
(
No. 985-2-119-121).
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