Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi

Article abstract of DOI:10.1016/j.bmcl.2011.04.036

Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2-3), and two new natural products (4-5), were isolated from the roots and rhizomes of Sinopodophyllum emodi together with twelve known lignans (6-17). Their structures and stereochemistry were elucidated on the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all isolated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1, 6-9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC ₅₀ values, deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-7′ might decrease cytotoxicity against two cell lines, which was different from most previous studies. However, this needs to be systematically verified by extensive pharmacological experiments.

Full text of DOI:10.1016/j.bmcl.2011.04.036

Bioorganic & Medicinal Chemistry Letters 21 (2011) 3794–3797
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi
Yan-Jun Sun a,b, Zhan-Lin Li a,b, Hong Chen c,d, , Xiao-Qiu Liu a, Wei Zhou a,b, Hui-Ming Hua a,b,
⇑
⇑
a Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China
b School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China
c Pharmacognosy Division, Medical College of Chinese People’s Armed Police Force, Tianjin 300162, PR China
d Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin 300162, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Three new aryltetralin lignans, 4-acetyl-4-demethyl-podophyllotoxin (1) and sinolignans A, B (2–3), and
two new natural products (4–5), were isolated from the roots and rhizomes of Sinopodophyllum emodi
together with twelve known lignans (6–17). Their structures and stereochemistry were elucidated on
the basis of spectroscopic evidence, and circular dichroism (CD) method. The cytotoxic activities of all iso-
lated compounds were evaluated against HeLa and KB cell lines. Compared with etoposide, compounds 1,
6–9, and 13 showed more potent cytotoxicities against two tumor cell lines. On the basis of IC50 values,
deoxypodophyllotoxin (7) was about 579 and 1123 times more toxic than etoposide in HeLa and KB cell
lines, respectively. The preliminary SAR study indicated that an oxygenated group at C-70 might decrease
cytotoxicity against two cell lines, which was different from most previous studies. However, this needs
to be systematically verified by extensive pharmacological experiments.
Received 14 February 2011
Revised 25 March 2011
Accepted 8 April 2011
Available online 19 April 2011
Keywords:
Sinopodophyllum emodi
Cytotoxic activities
Aryltetralin lignans
Ó 2011 Elsevier Ltd. All rights reserved.
The aryltetralin lactone podophyllotoxin occupies a unique po-
sition among lignan natural products since its glucopyranoside
derivatives, etoposide and teniposide, have been developed as clin-
ically useful anticancer medicines. Although they are active in the
treatment of many cancers and are widely used in the therapy, it
presents several limitations, such as moderate potency, poor water
solubility, development of drug resistance, metabolic inactivation,
and toxic effects.1,2 To improve its clinical efficacy and reduce side
effects, extensive structural modification of podophyllotoxin and
an ongoing search for new podophyllotoxin derivatives from natu-
ral medicines have been conducted in numerous laboratories.3–7
Sinopodophyllum emodi (Wall.) Ying is a folk-medicine used for
treating cancer, and various verrucosis in the southwest of China.3
Previous chemical and pharmacological investigations on S. emodi
revealed the presence of bioactive aryltetralin lignans,3–6 and cyto-
toxic and radioprotective properties.8 In a continuation of our
search for cytotoxic natural products, we herein described the iso-
lation, structure elucidation and evaluation of cytotoxic activity of
seventeen aryltetralin lignans (Fig. 1) along with their preliminary
structure–activity relationships.
phy, allowing the isolation of three new lignans (1–3), two new
natural products (4–5), and twelve known lignans.
Compound 1 was obtained as white needles and possessed a
molecular formula C23H22O9, as revealed from its TOF-ESI-MS anal-
ysis (m/z 465.1163 [M+Na]+, calcd for 465.1162).9 The 1H NMR
spectrum showed signals of two methoxyl groups at d 3.70 (6H,
s), four aromatic protons at d 7.11 (1H, s), 6.51 (1H, s), 6.41 (2H,
s), methylenedioxy group protons at 5.97 (1H, s), 5.96 (1H, s),
and a methyl proton at d 2.30 (3H, s). The 13C NMR spectrum re-
vealed a skeleton of aryltetralin lactone lignan including one car-
bonyl group at
d 174.5, twelve aromatic carbons and five
aliphatic carbons, besides two methoxyl groups at d 56.3 (ꢀ2),
one acetyl at d 169.1, 20.6, one methylenedioxy group at d
101.6.10 A careful comparison of the NMR spectra of 1 with 4-dem-
ethylpodophyllotoxin indicated that compound 1 was an acetyla-
tion derivative of 4-demethyl-podophyllotoxin, which was
confirmed by detailed analysis of the HSQC and HMBC spectra.
The HMBC correlation between the signal at d 127.9 (C-4) and d
2.31 (COCH3), indicated that acetoxyl was located at C-4 of 4-dem-
ethyl-podophyllotoxin.
The 95% EtOH extract of the roots and rhizomes of S. emodi
(18.8 kg) was partitioned between petroleum ether (PE), CHCl3,
n-BuOH and water, respectively. The PE, CHCl3 and n-BuOH layers
were fractionated and purified by repeated column chromatogra-
Establishment of the relative configuration was based on the 1H
0
coupling constants (J values) and NOESY experiment. The JH-8/H-8
0
0
(14.2 Hz) and JH-8 /H-7 (9.0 Hz) values indicated the trans-form of
H-8/H-80 and H-80/H-70.6,11–13 The JH-7/H-8 value was 3–5 Hz for
cis-configuration of H-7/H-8 and 7–9 Hz for the trans-configura-
tion.4–6 Compound 1 gave JH-7/H-8 = 4.4 Hz, indicating cis-configura-
tion of H-7/H-8. The relative configuration was further confirmed
by NOESY experiment. NOE of H-7/H-70, H-7/H-8, H-8/H-70 indi-
cated H-7, H-8, H-70 were at the same face. Studies on the ORD
⇑
Corresponding authors. Tel./fax: +86 22 60578193 (H.C.); tel./fax: +86 24
23986465 (H.-M.H.).
E-mail addresses: Chenhongtian06@yahoo.com.cn (H. Chen), huimhua@163.com
(H.-M. Hua).
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.04.036

Y.-J. Sun et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3794–3797
3795
OH
OR
R2
OH
OR
O
O
2
7
9
HO
HO
O
O
O
10
A
O
D
C
B
5
9
O
O
7
O
O
6
2
E
H3CO
OCH3
H3CO
OCH3
H3CO
OCH3
10
12
OR1
11
4 R=CH3
5 R=H
10 R=CH3
1 R1=COCH3 R2=α-OH
11 R=H
1
2
α
2 R =CH3 R = -6 acetyl-O-β-D-glc
6 R1=CH3 R2=α-OH
7 R1=CH3 R2=H
R2
O
O
O
O
O
O
O
O
8 R1=H R2=H
O
1
2
α
9 R =H R = -OH
H3CO
OCH3
13 R1=H R2=β-O-β-D-glc
H3CO
OCH3
OCH3
OR1
1
2
α
14 R =H R = -O-β-D-glc
3 R1=H R2=O-β-D-glc-6-glc
17 R1=CH3 R2=O-β-D-glc-6-glc
1
2
α
15 R =CH3 R = -O-β-D-glc
16 R1= O-β-D-glc R2=H
12
Figure 1. Structures of compounds 1–17 from S. emodi.
and CD curves of 7-aryltetralin lignans showed that all 7b (S)-aryl
5.95 (1H, s), 5.84 (1H, s). The 13C NMR spectrum exhibited one
carbonyl group at d 174.6, twelve aromatic carbons and five ali-
phatic carbons, besides two methoxyl groups at d 56.1 (ꢀ2), one
methylenedioxy group at d 100.7, two sets of glucopyranosyl
groups at d 103.7, 73.8, 77.0, 70.4, 76.8, 68.1, 103.2, 73.5, 76.4,
70.0, 76.4, 61.0. The aglycone was identified as picropodophyllo-
toxin by comparison of its NMR data with those reported in the lit-
erature,16 combined with correlations observed in the NOESY,
HSQC and HMBC spectra. The 13C NMR chemical shifts and spin-
spin coupling constants (7.6, 8.1 Hz) of two anomeric protons al-
lowed the identification of two b-glucopyranosyl moieties. The
absolute configuration of glucose was determined by a microhy-
drolysis method and GC analysis.17 The cross peaks of the anomeric
proton at d 4.49 (H-100) with C-70 (d 76.4) and the other anomeric
proton d 4.07 (H-1000) with C-600 at d 68.1, indicated that one gluco-
pyranosyl was at C-70 of the aglycone and the another was substi-
tuted at C-600 of the inner glucose.
compounds gave negative Cotton effects at around 280–290 nm,
while all 7
a
(R)-aryl compounds gave positive Cotton effect.5 The
CD spectrum of compound 1 exhibited positive Cotton effect at
288 nm. Consequently, the absolute configuration of C-7 was
determined to be R. Thus, compound 1 was established as 4-acet-
yl-4-demethyl-podophyllotoxin.
Compound 2 was obtained as amorphous powder and pos-
sessed a molecular formula C30H34O14, as revealed from its QFT-
ESI-MS analysis (m/z 641.1845 [M+Na]+, calcd for 641.1846).14
The 1H NMR spectrum showed proton signals of three methoxyl
groups at d 3.62 (6H, s), 3.61 (3H, s), four aromatic protons at d
7.35 (1H, s), 6.54 (1H, s), and 6.30 (2H, s), methylenedioxy group
protons at 6.00 (1H, s), 5.98 (1H, s), methyl protons at d 1.63
(3H, s). The 13C NMR spectrum revealed a skeleton of aryltetralin
lactone lignan including one carbonyl group at d 174.6, twelve aro-
matic carbons and five aliphatic carbons, besides three methoxyl
groups at d 55.9 (ꢀ2), 60.0, 6-acetyl-glucopyranosyl at d 100.8,
73.4, 76.4, 70.4, 74.0, 63.8, 170.1, 20.0, and one methylenedioxy
group at d 101.2.10 A careful comparison of the NMR spectra of 2
0
0
0
The JH-7/H-8 (8.2 Hz), JH-8 /H7 (9.7 Hz) and JH-8/H-8 (9.7 Hz) values
combined with NOE correlation of H-7/H-70 and H-8/H-80 deter-
mined the relative configuration of 7,8-trans-80,70-trans-8,80-cis.
Compound 3 gave positive Cotton effects at 288 nm, indicating
the absolute configuration of C-7 to be R. Thus, compound 3 was
with podophyllotoxin-4-O-b-
pound 2 to be an acetylation derivative of podophyllotoxin-4-O-
b- -glucopyranoside. This assignment was confirmed by detailed
D-glucopyranoside suggested com-
D
deduced as 4-demethyl-picropodophyllotoxin-70-O-b-
anosyl-(1?6)-b- -glucopyranoside, and named sinolignan B.
D-glucopyr-
analysis of the HSQC and HMBC spectra. The HMBC correlations
between the signal at d 170.1 (C-700) and d 4.31, 3.95 (H-600) indi-
cated that acetoxyl was located at C-6 of glucopyranosyl group.
D
By comparing physical and spectroscopic data with literatures,
the fourteen known constituents were identified as 30,40-demethyl-
ene-podophyllotoxin (4),18,19 30,40-demethylene-4-demethyl-podo-
phyllotoxin (5),18,19 podophyllotoxin (6),6 deoxypodophyllotoxin
(7),6 4-demethyl-deoxypodophyllotoxin (8),6 4-demethyl-podophyl-
lotoxin (9),6 dehydropodophyllotoxin (10),20 4-demethyl-dehydrop-
odophyllotoxin (11),20 isopicropodophyllone (12),6 4-demethyl-
0
0
0
The JH-8/H-8 (14.5 Hz), JH-8 /H7 (10.2 Hz) and JH-7/H-8 (4.9 Hz) values
and NOE correlation of H-7/H-70, H-8/H-70 indicated that 2 pos-
sessed the same relative configuration as podophyllotoxin.2–5 The
CD spectrum of compound 2 gave positive Cotton effect at
289 nm, so the absolute configuration of C-7 was determined to
be R. Thus, compound 2 was deduced as 600-acetyl-podophyllo-
epipodophyllotoxin-70-O-b-
podophyllotoxin-70-O-b- -glucopyranoside (14),4 podophyllotoxin-
70-O-b- -glucopyranoside (15),4 4-demethyl-deoxypodophyllotoxin-
4-O-b-
-glucopyranoside (16),21 and picropodophyllotoxin-70-O-b-
-glucopyranosyl-(1?6)-b-
-glucopyranoside (17).5
D
-glucopyranoside (13),3 4-demethyl-
toxin-70-O-b-
D-glucopyranoside, and named sinolignan A.
D
Compound 3 was obtained as amorphous powder and its
molecular formula was determined as C33H40O18 on the basis of
its QFT-ESI-MS (m/z 747.2096 [M+Na]+, calcd for 747.2112).15
The 1H NMR spectrum showed proton signals of two methoxyl
groups at d 3.74 (6H, s), four aromatic protons at d 7.22 (1H, s),
5.96 (1H, s), 6.58 (2H, s), methylenedioxy group proton signals at
D
D
D
D
All isolated compounds were tested for their in vitro cytotoxic
activity against HeLa and KB cell lines using MTT assay (Table 2).22
Compound 7 showed the highest cytotoxicity against HeLa cell line

3796
Y.-J. Sun et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3794–3797
Table 1
1H NMR and 13C NMR spectroscopic data for compounds 1–3
Position
1a
dH (J in Hz)
2b
3b
dH (J in Hz)
dC
dC
dH (J in Hz)
dC
1
2
3
4
5
6
7
8
138.5
107.9
151.6
127.9
151.6
107.9
44.3
136.5
108.4
152.1
136.7
152.1
108.4
43.3
132.1
106.6
148.0
134.2
148.0
106.6
44.3
6.41, s
6.30, s
6.58, s
6.41, s
4.61, d, 4.4
2.85, dd, 4.4, 14.2
6.30, s
4.53, d, 4.9
3.17, dd, 4.9, 14.5
6.58, s
3.85, d, 8.2
3.43, dd, 9.7, 8.2
45.4
44.6
44.3
9
174.7
130.9
106.6
147.8
147.8
109.9
133.5
72.7
174.6
130.9
107.9
146.8
147.1
109.4
132.3
78.6
38.3
71.2
55.9
60.0
178.0
132.3
105.8
145.5
146.1
107.5
132.8
76.4
10
20
7.11, s
6.51, s
7.35, s
7.22, s
5.96, s
30
40
50
6.54, s
60
70
4.73, d, 9.0
2.78, m
4.56, dd, 9.0, 7.1; 4.03, dd, 9.6, 9.0
3.70, s
4.97, d, 10.2
2.80, m
4.46, dd, 8.5, 7.6; 4.15, dd, 10.3, 8.5
3.62, s
3.61, s,
3.62, s
5.98, s; 6.00, s
4.28, d, 7.5
3.10, m
3.15, m
3.07, m
3.24, m
4.62, d, 10.0
2.76, m
4.57, dd, 9.5, 1.1; 4.42, dd, 9.5, 6.7
3.74, s
80
40.7
71.6
56.1
42.1
68.9
56.1
90
10
11
12
100
100
200
300
400
500
600
1000
2000
3000
4000
5000
6000
COCH3
56.3
101.6
3.70, s
5.96, s; 5.97, s
55.9
56.1
100.7
103.7
73.8
77.0
70.4
76.8
68.1
103.2
73.5
76.4
70.0
76.4
61.0
3.74, s
101.2
100.8
73.4
76.4
70.4
5.84, s; 5.95, s
4.49, d, 7.6
3.19, m
3.24, m
3.07, m
74.0
63.8
3.41, m
4.31, dd, 1.9, 11.2; 3.95, dd, 8.3, 11.2
3.93, br d,11.3; 3.52, m
4.07, d, 7.6
2.84, m
2.54, m
2.94, m
2.69, m
3.56, m; 3.35, dd, 5.7, 11.7
169.0
20.6
170.1
20.0
2.31, s
1.63, s
a
NMR spectroscopic data were recorded in CDCl3 at 300 MHz (1H NMR) and 75 MHz (13C NMR).
b
NMR spectroscopic data were recorded in DMSO-d6 at 300 MHz (1H NMR) and 75 MHz (13C NMR).
Table 2
Cytotoxic activities of compounds 1–17 against HeLa and KB cell lines
c
c
Compound
IC50
(
lM)
Compound
IC50
(lM)
HeLa
KB
HeLa
KB
1
2
3
4
5
6
7
8
9
0.076 0.005
3.77 0.32
>100
>100
79.6 6.8
0.05 0.003
8.76 0.75
>100
>100
>100
10
11
12
13
14
15
16
17
8.28 0.79
>100
9.79 0.9
84.7 8.1
>100
32.1 3.11
0.048 0.004
5.33 0.42e
6.65 0.58d
0.87 0.06
>100
<0.01
9.51 0.7e
9.25 0.8d
2.09 0.2
>100
0.069 0.005d
0.0069 0.0005
0.074 0.006
0.08 0.005
0.056 0.004d
0.0089 0.0006
0.0078 0.0006
0.064 0.005e
Etoposide
4.0 0.3
10.0 0.9
c
IC50 is defined as the concentration of drug required to inhibit cell growth by 50% compared with untreated control; It is expressed as mean SD of at least three
determinations.
d
Significant differences are indicated as: p <0.05 compared with compound 7.
Significant differences are indicated as: p <0.05 compared with compound 8.
e
and compound 8 was the most active against KB cell line. The
7
structurally required for the cytotoxicity against HeLa and KB cells
lines. The ring A-opened compounds (4 and 5) were found to be
less potent than the methylenedioxy-bearing analogues (6 and
9). Methylation and acetylation of a free hydroxyl at C-4 did not
significantly influence the cytotoxic activity, for example, com-
pared 6 and 1 to 9, and 15 to 14.
The remarkable biological activity makes podophyllotoxin an
important starting product for the development of new therapeutic
agents.7 Extensive structural modifications of podophyllotoxin
have been undertaken to obtain more active and less toxic antitu-
0a-hydroxy derivatives 6, 15, and 9, 14 exhibited significantly
lower activity compared to compounds 7 and 8 without 70-substi-
tution. The glycosylation of the 70a-hydroxy group (9 and 6) with a
glucose moiety (14 and 15) strongly reduced the activity. The con-
figuration at C-70 is important, as 70b-glucosyl derivative 13
showed more potent activity than 70a-glucosyl compounds 14
and 15. Compounds 6 and 9 containing a non-aromatized ring C
showed to have more cytotoxic activity than aromatized com-
pounds 10 and 11, indicating that a non-aromatized ring C was

Y.-J. Sun et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3794–3797
3797
mor agents. On the basis of the published SAR studies related
References and notes
podophyllotoxin analogues, the substitution and configuration at
C-70, a methylenedioxy at ring A, non-aromatized ring C, and a
trans-fusion between the tetraline and lactone, play a very impor-
tant role in maintaining cytotoxicity for this series of com-
pounds.7,23–27 C-70 position was the only molecular area tolerable
to significant structural diversification and resulted in a number
of promising candidates. Most of research efforts have been fo-
cused on exploring different 70-substituted podophyllotoxin ana-
logues.7 Position 70 was very important in antimitotic activity.28
However, disappearance of the free hydroxyl group at C-70 did
not elicit significant variations in the antitumor activity.28 Deoxyp-
odophyllotoxin (7) showed stronger cytotoxicity than podophyllo-
toxin (6) against GLC4 cell line.23 Podophyllotoxin analogues (6, 15
and 9, 14) with 70a oxygenated group exhibited significantly lower
activity than corresponding analogues (7 and 8) without 70-substi-
tution, which suggested that 70-substitution may be not essential
for cytotoxicity in podophyllotoxin-type compounds. Novel
analogues with no substitution at C-70 would be necessarily
designed and synthesized to obtain new antitumor agents.
The continuous search of natural podophyllotoxin analogues
from medicinal plants or their tissue cultures was carried out by nat-
ural products chemists. More than 40 aryltetralin lignans have been
isolated from the plants of genus Sinopodophyllum, Podophyllum,
Dysosma, Diphylleia (Berberidaceae), Linum (Linaceae), Libocedrus
(Cupressaceae), Bursera (Burseraceae), etc.3–6,13,20,21,29–34 A few of
them were tested for the cytotoxic activity in tumor cell lines.30–34
The phytochemical studies on S. emodi resulted in the isolation of
17 aryltetralin lignans including three new compounds (1–3), two
new natural products (4–5). Compounds 4 and 5 represent the first
report of ring A-opened podophyllotoxin analogues from Sinopodo-
phyllum. Most compounds showed moderate to high activity against
HeLa and KB cell lines. Compounds 7 and 8 were the most interesting
of the isolated compounds based upon their IC50 values. Based on
these preliminary results obtained by us, further studies on
compound 7 are necessary to explore antitumor mechanism and
cytotoxicities in normal cells.
1. Zhu, X. K.; Guan, J.; Tachibana, Y.; Bastow, K. F.; Cho, S. J.; Cheng, H. H.; Cheng,
Y. C.; Gurwith, M.; Lee, K. H. J. Med. Chem. 1999, 42, 2441.
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Q.; Lee, K. H. J. Med. Chem. 2004, 47, 5140.
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4. Zhao, C. Q.; Huang, J.; Nagatsu, A.; Ogihara, Y. Chem. Pharm. Bull. 2001, 49, 773.
5. Zhao, C. Q.; Nagatsu, A.; Hatano, K.; Shirai, N.; Kato, S.; Ogihara, Y. Chem. Pharm.
Bull. 2003, 51, 255.
6. Jackson, D. E.; Dewick, P. M. Phytochemistry 1984, 23, 1147.
7. Liu, Y. Q.; Yang, L.; Tian, X. Curr. Bioact. Compd. 2007, 3, 37.
8. Shukla, S. K.; Chaudhary, P.; Kumar, I. P.; Afrin, F.; Puri, S. C.; Qazi, G. N.;
Sharma, R. K. Environ. Toxicol. Pharmacol. 2006, 22, 113.
9. 4-Acetyl-4-demethyl-podophyllotoxin (1): white needle (CHCl3); mp 231–
233 °C; ½a DD
ꢁ
ꢂ98.1 (c 0.8, CHCl3); UV (MeOH) kmax (log
e
) 208 (1.8), 292 (0.1);
max 3495,
CD (MeOH) kmax (De) 232 (+4.1), 265 (ꢂ2.6), 288 (+1.6) nm; IR (KBr) m
2893, 1764, 1603, 1508, 941 cmꢂ1; NMR data (CDCl3), see Table 1; TOF-ESI-MS
m/z 465.1163 [M+Na]+ (calcd for C26H34O12Na, 465.1162).
10. Casanovas, J.; Namba, A. M.; Silva, R. D.; Alemán, C. Bioorg. Chem. 2005, 33, 484.
11. Broomhead, A. J.; Dewick, P. M. Phytochemistry 1990, 29, 3839.
12. Yu, P. Z.; Wang, L. P.; Chen, Z. N. J. Nat. Prod. 1991, 54, 1422.
13. Vasilev, N. P.; Ionkova, I. I. Phcog. Mag. 2006, 2, 172.
14. Sinolignan A (2): amorphous powder; ½a D25
ꢁ
ꢂ79.1 (c 0.5, MeOH); UV (MeOH)
kmax (log e) 208 (1.7), 288 (0.2); CD (MeOH) kmax (De
) 234 (+74.1), 266 (ꢂ17.8),
289 (+2.9) nm; IR (KBr) mmax 3440, 2936, 1772, 1738, 1590, 1506, 1239, 1127,
1037, 931 cmꢂ1; NMR data (DMSO-d6), see Table 1; ESI-MS m/z 641 [M+Na]+,
657 [M+K]+, 653 [M+Cl]ꢂ, 663 [M+HCOOꢂ]+; QFT-HR-ESI-MS m/z 641.1845
[M+Na]+ (calcd for C30H34O14Na, 641.1846).
15. Sinolignan B (3): Amorphous powder(MeOH); ½a D25
ꢁ
-40.0 (c 0.2, MeOH); UV
(MeOH) kmax (log e) 208 (2.1), 284 (0.3); CD (MeOH) kmax (De) 224 (+2.2), 264
(ꢂ1.1), 288 (+1.0) nm; IR (KBr)
mmax 3425, 2919, 1772, 1769, 1618, 1523, 1265,
1120, 1035, 929 cmꢂ1; NMR data (DMSO-d6), see Table 1; ESI-MS: m/z 747
[M+Na]+, 763 [M+K] +, 723 [MꢂH]ꢂ; QFT-HR-ESI-MS m/z 747.2096 [M+Na]+,
(calcd for C33H40O18Na, 747.2107).
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Acknowledgments
The authors wish to thank Professor Qishi Sun (Shenyang
Pharmaceutical University, Shenyang, People’s Republic of
China) for identification of the plant material. This work was sup-
ported by the National Natural Science Foundation of China (No.
30873363), Program of Science Foundation of Tianjin
(08JCYBJC070000) and Major Program of Science Foundation of
Tianjin (09ZCKFSH01700).
Supplementary data
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Supplementary data (spectra of compounds 1–3 along with the
general experimental details, extraction and isolation, acid hydro-
lysis and sugar determination, and in vitro cytotoxicity assays)
associated with this article can be found, in the online version, at
doi:10.1016/j.bmcl.2011.04.036.
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