A new phenolic glycoside from the stem of Dendrobium nobile

Article abstract of DOI:10.1080/14786419.2016.1266352

A new phenolic glycoside dendroside (1), together with seven known compounds (2–8) were isolated from the stems of Dendrobium nobile. The structures of these compounds were elucidated using comprehensive spectroscopic methods. The inhibitory activities of all compounds against three cancer cell lines HeLa, MCF-7 and A549 were evaluated.

Full text of DOI:10.1080/14786419.2016.1266352

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
A new phenolic glycoside from the stem of
Dendrobium nobile
Xue-Ming Zhou, Cai-Juan Zheng, Jia-Ting Wu, Guang-Ying Chen, Bin Zhang &
Chong-Ge Sun
To cite this article: Xue-Ming Zhou, Cai-Juan Zheng, Jia-Ting Wu, Guang-Ying Chen, Bin Zhang &
Chong-Ge Sun (2016): A new phenolic glycoside from the stem of Dendrobium nobile, Natural
Product Research
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Date: 11 December 2016, At: 06:13

Natural Product research, 2016
ꢁꢁp://ꢂx.ꢂꢃi.ꢃꢄg/10.1080/14786419.2016.1266352
ꢀ
A new phenolic glycoside from the stem of Dendrobium nobile
a
a
a
a
a
Xue-Ming Zhou , Cai-Juan Zheng , Jia-Ting Wu , Guang-Ying Chen , Bin Zhang and
Chong-Ge Sunb
ꢅ
Kꢆy lꢅbꢃꢄꢅꢁꢃꢄy ꢃf tꢄꢃpiꢇꢅꢈ Mꢆꢂiꢇinꢅꢈ Pꢈꢅnꢁ cꢀꢆmiꢉꢁꢄy ꢃf Miniꢉꢁꢄy ꢃf eꢂꢊꢇꢅꢁiꢃn, cꢃꢈꢈꢆgꢆ ꢃf cꢀꢆmiꢉꢁꢄy ꢅnꢂ
b
cꢀꢆmiꢇꢅꢈ enginꢆꢆꢄing, hꢅinꢅn Nꢃꢄmꢅꢈ univꢆꢄꢉiꢁy, hꢅikꢃꢊ, Pꢆꢃpꢈꢆ’ꢉ rꢆpꢊbꢈiꢇ ꢃf cꢀinꢅ; hꢅinꢅn Bꢃying oꢄꢇꢀiꢂ
Inꢂꢊꢉꢁꢄiꢅꢈ dꢆvꢆꢈꢃpmꢆnꢁ cꢃ lꢁꢂ., hꢅikꢃꢊ, Pꢆꢃpꢈꢆ’ꢉ rꢆpꢊbꢈiꢇ ꢃf cꢀinꢅ
ABSTRACT
ARTICLE HISTORY
A new phenolic glycoside dendroside (1), together with seven known
compounds (2–8) were isolated from the stems of Dendrobium
nobile. The structures of these compounds were elucidated using
comprehensive spectroscopic methods. The inhibitory activities of
all compounds against three cancer cell lines HeLa, MCF-7 and A549
were evaluated.
rꢆꢇꢆivꢆꢂ 7 sꢆpꢁꢆmbꢆꢄ 2016
aꢇꢇꢆpꢁꢆꢂ 15 Nꢃvꢆmbꢆꢄ 2016
KEYWORDS
oꢄꢇꢀiꢂꢅꢇꢆꢅꢆ; Dendrobium
nobile; gꢈyꢇꢃꢉiꢂꢆ; ꢇyꢁꢃꢁꢃxiꢇ
ꢅꢇꢁiviꢁy
1
. Introduction
The genus Dendrobium (Orchidaceae) are mainly distributed throughout Asia, Europe and
Australia. The stems of several Dendrobium species are used as a traditional medicine (Wang
et al. 1985; Lee et al. 1995; Zhao et al. 2001, 2016; Zhang et al. 2007; Sun et al. 2014).
Dendrobium nobile, widely distributed in China, is not only an ornamental but also a medic-
inal plant and many farmers grow D. nobile as an ornamental plant in China. Our previous
study on D. nobile has led to the isolation of 23 phenanthrene derivatives and five bibenzyl
derivatives, some of the isolated products showed cytotoxic or antifungal activities (Zhou,
Zheng, Gan et al. 2016). In our ongoing investigation of natural cytotoxic products, a new
phenolic glycoside dendroside (1) together with seven known compounds were isolated
from the stems of D. nobile. All compounds were tested for their cytotoxic activities on three
cancer cell lines.
CONTACT Gꢊꢅng-Ying cꢀꢆn
ꢇꢀgying123@163.ꢇꢃm
sꢊppꢈꢆmꢆnꢁꢅꢈ ꢂꢅꢁꢅ fꢃꢄ ꢁꢀiꢉ ꢅꢄꢁiꢇꢈꢆ ꢇꢅn bꢆ ꢅꢇꢇꢆꢉꢉꢆꢂ ꢅꢁ ꢀꢁꢁp://ꢂx.ꢂꢃi.ꢃꢄg/10.1080/14786419.2016.1266352.
©
2016 Infꢃꢄmꢅ uK limiꢁꢆꢂ, ꢁꢄꢅꢂing ꢅꢉ tꢅyꢈꢃꢄ & Fꢄꢅnꢇiꢉ Gꢄꢃꢊp

2
X.ꢀM. ZHOU ET AL.
2
. Results and discussion
Compound 1 was obtained as white amorphous powder, with the molecular formula
1
13
C H O from HRESIMS data combined with H and C NMR spectroscopic data (Supporting
30 34 13
1
information, Table S1). The H NMR data revealed four olefinic protons δ 7.72 (2H, d, 16) and
H
δ 6.55 (2H, d, 16), 10 aromatic protons δ 7.61 (4H, m) and δ 7.41 (6H, m) together with
H
H
H
13
many protons arising from sugar moiety. The C NMR data showed 30 resonances, including
2
1
ester carboxyl carbons (δ 168.6 and 168.5), 4 olefinic carbons (δ 146.5, 146.4, 118.8 and
18.7), 12 benzene ring carbons and 12 oxygenated carbons. These data indicated that
C
C
compound 1 was comprised of two trans-cinnamic acid subunits and two glucose subunits.
The anomeric protons and carbons of glucose subunits at δ 5.11 (1H, d, 4.0), δ 94.0 and δ
H
C
H
4
.51 (1H, d, 7.6), δ 98.3, respectively. These data suggested that the two glycosyl moieties
C
were α-glucose and β-glucose, respectively. The location of the glycosyl moieties (C-6′ and
C-6′a) at C-1 and C-1a were confirmed by the HMBC correlations between H-6′ and C-1, H-6′a
and C-1a, respectively. The linkage of two glucose subunits was also confirmed by the HMBC
correlation between H-1′ and C-1′a. Acid hydrolysis of 1 with 2 M HCl produced an α-glucose
and a β-glucose (They were separated by the semi-preparative HPLC; MeOH/H O, 10:90).
2
2
4
The α-glucose showed a positive optical rotation,[ꢀ] +44.8 (c 0.1, H O), and indicated that
D
2
2
4
it was α-d-glucose. The β-glucose showed a positive optical rotation,[ꢀ] +19.2 (c 0.1, H O).
D
2
These data indicated that it was β-d-glucose. Thus, compound 1 was identified as a new
phenolic glycoside (Figure 1). And we named compound 1 as dendroside.
The structures of known compounds, isorhamentin-3-O-β-d-rutinoside (2) (Comte et al.
1996), adenosine (3) (Lai & Lee 2013), 4-methoxy-2,5,9R-trihydroxy-9,10-dihydrophenan-
threne 2-O-β-d-glucopyranoside (4) (Lin et al. 2013), (7S,8R) dehydrodiconiferyl alcohol
O
O
OH O 1a 3a
OH
7
9a
NH2
HO
O
O
N
N
N
HO
HO
9
5
7a
6
'a
5a
3
N
O
'a
O
OH
OH
1
OH
OH
1
O
O 1' O
O
O
O 6'
3
1
O
O
OH
HO
OH
OH
OH
OH
HO
OH
2
OH
O
OH
O
OH
O
HO
HO
HO
HO
O
OH
OH
O
HO
O
O
HO
OH
OH
5
O
HO
O
OH
O
6
4
O
HO
OH
O
OH
HO
HO
HO
OH
O
O
O
HOH C
2
CH OH
2
OH
OH
O
O
O
O
HO
O
O
O
7
OH
8
Figure 1. sꢁꢄꢊꢇꢁꢊꢄꢆꢉ ꢃf ꢇꢃmpꢃꢊnꢂꢉ 1–8 iꢉꢃꢈꢅꢁꢆꢂ fꢄꢃm D. nobile.

NATURAL PRODUCT RESEARCH
3
Table 1. tꢀꢆ ꢇyꢁꢃꢁꢃxiꢇ ꢅꢇꢁiviꢁiꢆꢉ ꢃf iꢉꢃꢈꢅꢁꢆꢂ ꢇꢃmpꢃꢊnꢂꢉ.
IC50 (μM)
Compounds
HeLa
MCF-7
A549
1
2
3
4
5
6
7
8
16.8
22.5
>100
38.9
40.8
>100
>100
37.0
0.5
22.3
26.8
>100
>100
53.1
>100
>100
51.1
0.8
19.8
23.3
89.5
42.3
49.6
>100
>100
46.7
1.0
ꢅ
epiꢄꢊbiꢇin
ꢅepiꢄꢊbiꢇin wꢅꢉ ꢊꢉꢆꢂ ꢅꢉ ꢅ pꢃꢉiꢁivꢆ ꢇꢃnꢁꢄꢃꢈ.
9′-β-glucopyranoside (5) (Jiang et al. 2001), koaburaside (6) (Kosuge et al. 1994; Zhou,
Zheng, Song et al. 2016), juniperoside (7) (Comte et al. 1996), and dehydrodiconiferyl-
alcohol-4-β-d-glucoside (8) (Arens et al. 1985) were identified by comparison of their
spectroscopic data with those in the literature.
All compounds were tested for cytotoxic activities against HeLa, MCF-7 and A549 cells
(
Table 1). Compounds 1 and 2 showed moderate inhibitory effects on HeLa, MCF-7 and A549
cells with IC values ranging from 16.8 to 26.8 μM.
5
0
3
. Experimental
3
.1. General
Optical rotations were measured on a JASCO P-1020 digital polarimeter. IR spectra were
recorded on a Nicolet 6700 spectrophotometer. NMR spectra were recorded on a Bruker AV
1
13
spectrometer (400 MHz for H and 100 MHz for C). TMS was used as an internal standard.
HRESIMS spectra were measured on a Q-TOF Ultima Global GAA076 LC mass spectrometer.
Semi-Preparative HPLC was performed on an Agilent 1260 LC series with a DAD detector
using an Agilent Eclipse XDB-C18 column (9.4 × 250 mm, 5 μm). Silica gel (Qing Dao HaiYang
Chemical Group Co; 200–300 mesh), octadecylsilyl silica gel (YMC; 12 nm–50 μm) were used
for column chromatography (CC). Precoated silica gel plates (Yan Tai Zi Fu Chemical Group
Co; G60, F-254) were used for thin layer chromatography.
3
.2. Plant material
The stems of D. nobile were provided by the Hainan Boying Orchid Industrial Development
Co, Ltd in June 2014. A voucher specimen (No. GFM20140612) has been deposited at the
Key Laboratory of Tropical Chemistry of Medicinal Plant of Ministry of Education, Hainan
Normal University (Hainan, China).
3
.3. Extraction and isolation
The air-dried and powdered stems (5 kg) of D. nobile were extracted with 70% EtOH (3 × 20 L,
days each) at room temperature. After concentration under reduced pressure, the water-sol-
uble residue was partitioned successively with petroleum ether and EtOAc. The EtOAc extract
5

4
X.ꢀM. ZHOU ET AL.
(
95 g) was separated using a silica gel CC (petroleum ether, EtOAc, MeOH v/v, gradient) to
generate seven fractions (Frs. 1–7). Frs. 7 (20 g) was applied to silica gel CC eluted with
EtOAc–MeOH (from 20:1 to 1:1) to afford three subfractions (3a–3c). Subfraction 3a was
further purified by using octadecylsilyl silica gel (10% MeOH/H O) to obtain 4 (8 mg), 6
2
(
12 mg) and 7 (21 mg). Subfractions 3b and 3c were further separated by semi-preparative
HPLC (CH CN/H O, 10:90 and 7:93 v/v) to obtain 3 (31 mg), 5 (13 mg), and 8 (18 mg); 1 (6 mg)
3
2
and 2 (22 mg), respectively.
3
.4. Dendroside (1)
2
4
White amorphous powder; [ꢀ] +52.8 (c 0.1, MeOH); IR (KBr) v 3425, 2928, 1712, 1638,
D
max
−1
−
1
1
577 and 1496 cm ; HR-ESI-MS m/z 601.1918 [M − H] (C H O ; calcd 601.1921); H NMR
30 33 13
(
MeOD-d , 400 MHz) δ: 7.72 (2H, d, J = 16.0 Hz, H-3/3a), 7.61 (4H, m, H-5/9/5a/9a), 7.41 (6H,
4
m, H-6/7/8/6a/7a/8a), 6.55 (2H, d, J = 16 Hz, H-2/2a), 5.11 (1H, d, J = 4.0 Hz, H-1′a), 4.51 (1H,
d, J = 7.6, H-1′), 4.29–4.55 (4H, m, H-6′/6′a), 4.05 (1H, m, H-5′a), 3.70 (1H, m, H-3′a), 3.54 (1H,
1
3
m, H-2′), 3.33–3.40 (4H, m, H-3′/4′/2′a/4′a), 3.17 (1H, m, H-5′); C NMR (MeOD-d ,100 MHz)
4
δ: 168.6 (C-1), 168.5 (C-1a), 118.8 (C-2), 118.7 (C-2a), 146.5 (C-3), 146.4 (C-3a), 135.7 (C-4/4a),
129.2 (C-5/9/5a/9a), 130.1 (C-6/8/6a/8a), 131.6 (C-7/7a), 98.3 (C-1′), 75.4 (C-2′), 78.0 (C-3′),
72.0 (C-4′), 76.2 (C-5′), 65.1 (C-6′), 94.0 (C-1′a), 73.8 (C-2′a), 74.8 (C-3′a), 71.8 (C-4′a), 70.8 (C-5′a),
65.0 (C-6′a).
3
.5. Hydrolysis of compound 1
Acid hydrolysis of compound 1: A solution of 1 (5 mg) in 2 M HCl (2 mL) was heated under
reflux for 4 h, and then evaporated to dryness. The mixture of 1 was extracted with EtOAc
(4 mL × 3). Finally, trans-cinnamic acid (2.2 mg) was obtained. The aqueous layer was further
separated by the semi-preparative HPLC (MeOH/H O, 10:90) to obtain an α-glucose (1.2 mg)
2
and a β-glucose (1 mg).
3
.6. Biological assays
Cytotoxic activity was evaluated by the MTT method as described previously (Scudiero
et al. 1988). HeLa, MCF-7 and A549 were provided by College of Pharmacy, Hebei University
and maintained in DMEM medium (Gibco) containing 5% foetal bovine serum (Gibco) at
3
7 °C in air with 5% CO . Compounds 1, 2, 5 and 8 showed moderate inhibitory effects on
2
HeLa, MCF-7, and A549 cells. The IC values of other compounds higher than 100 μM were
5
0
regarded as inactive.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the Industry-University-Research Cooperation Integration Program of
Hainan Province [grant number SQ20150CXY0064]; the Hainan Province Natural Science Foundation

NATURAL PRODUCT RESEARCH
5
of Innovative Research Team Project [grant number 2016CXTD007]; the Innovative Research Topics of
Hainan province Regular IHEs [grant number Hyb2016-15].
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