New alkaloid and aromatic glucoside from the flowers of cymbidium lunagrad eternal green

Article abstract of DOI:10.3390/molecules23010099

In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (1), and a new aromatic glucoside, named Lunagrad B (2), were isolated from the MeOH extract of the flowers of Cymbidium Lunagrad Eternal Green, along with other six known aromatic compounds (3–8) and three flavone glucosides (9–11). These structures were determined on the basis of NMR experiments, as well as chemical evidence.

Full text of DOI:10.3390/molecules23010099

molecules
Article
New Alkaloid and Aromatic Glucoside from the
Flowers of Cymbidium Lunagrad Eternal Green
Li-Yan Song, Fang Huang, Yan Wang, Zu-Jian Wu and Ming-An Ouyang *
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Institute of Plant Virology,
Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China; slywinter@163.com (L.-Y.S.);
fafuhf12@163.com (F.H.); fafuwy12@163.com (Y.W.); wuzujian@126.com (Z.-J.W.)
*
Correspondence: minganouyang@163.com; Tel.: +86-150-059-957-02
Received: 30 November 2017; Accepted: 30 December 2017; Published: 3 January 2018
Abstract: In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad
Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (
and a new aromatic glucoside, named Lunagrad B ( ), were isolated from the MeOH extract of the
flowers of Cymbidium Lunagrad Eternal Green, along with other six known aromatic compounds (3–8)
and three flavone glucosides ( 11). These structures were determined on the basis of NMR
1),
2
9–
experiments, as well as chemical evidence.
Keywords: orchid; Cymbidium Lunagrad Eternal Green; alkaloid; aromatic glucoside; flavone glycoside
;
natural product
1
. Introduction
Since ancient times, numerous orchid species have been used in different countries for apparent
ornamental and medicinal value. Cymbidium hybridum is one of the most popular pot orchids
worldwide, which contains a huge number of cultivars with large flowers. Commercial Cymbidium
hybridum includes some wild species in genus of Cymbidium and lots of hybrid cultivars through
inter-specific hybridization between 20 Cymbidium species of terrestrial and epiphytic orchids.
The natural parent species of Cymbidium hybridum could trace back to its primal putative parents
Cymbidium eburneum (maternal parent) and Cymbidium lowianum (paternal parent) in 1889 [1–3].
However, very little is known about the chemical or bioactive substances of these cultivars. To the best
of our knowledge, only one Cymbidium hybridum, Cymbidium Great Flower Marylaurencin, has been
chemically investigated, leading to the identification of phenanthrene derivatives and aromatic
constituents, which showed certain biological activities [4–7].
In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad
Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (1)
and a new aromatic glucoside, named Lunagrad B ( ), were isolated (Figure 1). We describe here
and , primarily determined by extensive
,
2
the isolation, purification, and structural elucidation of
NMR experiments.
1
2
In addition, six known aromatic compounds (2R)-2-benzyl-2-hydroxysuccinic acid (
marylaurecinosides B ( ) [ ], grammatophylloside B ( ) [ ], gastrodin ( ) [10], arbutin (
and sakakin ( ) [12], together with three flavone glucosides, ermanin ( ) [13], quercetin
-L-rhamnopyranosyl- -D-glucopyranoside (10) [14], and orientin (11) [15] were found.
The known structures (Figure 2) were identified by comparison of their spectroscopic data with those
3) [
8],
4
5
5
9
6
7) [11],
8
9
0
0
3
-O-
α
-(2 -O-
α
β
reported in the literature. It is noteworthy that compounds
3–
8
were also obtained from the flowers of
Cymbidium Great Flower Marylaurencin [7].
Molecules 2018, 23, 99; doi:10.3390/molecules23010099
www.mdpi.com/journal/molecules

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Figure 1. Two new compounds 1 and 2 isolated from the flowers of Cymbidium Lunagrad Eternal Green.
Figure 2. Nine known compounds 3–11 isolated from the flowers of Cymbidium Lunagrad Eternal Green.
2
. Results and Discussion
Lunagrad A (1) was identified as a bisbenzyltetrahydroisoquinoline alkaloid (BBIQA) derivative.
The BBIQAs represent a large and important class of natural products, which have received great
attention due to their wide range of pharmacological activities [16
as a slightly yellow amorphous powder and showed an [M + H] ion peak at m/z = 641.3230
–
21]. Compound
1
was obtained
+
(
calcd. 641.3227) in the HR-MS (ESI), which corresponded to the molecular formula C H N O .
C-NMR, edited HSQC, and HMBC spectra (Supplementary Information Figures S3–S8) of
38 44 2 7
1
3
compound 1 displayed 38 carbon resonances, assignable to ten aromatic tertiary carbons
(
(
δC 107.3, 113.2, 113.7, 116.7, 121.4, 122.8, 122.9, 124.4, 131.8, 133.9), 14 aromatic quaternary carbons
124.0, 129.0, 129.1, 129.3, 135.8, 136.7, 139.3, 153.0, 149.4, 148.7, 151.0, 150.3, 145.2, 155.1),
δ
C
two aliphatic methines (
δ 63.0, 64.5), six aliphatic methylenes (δ 23.7, 26.0, 37.5, 42.6, 45.3, 45.7),
C
C
two NCH (δ 42.5, 43.1), and four OCH groups (
δ 56.1, 56.4, 56.8, 60.7) that are connected to
C
3
C
3
aromatic rings. The NMR data featured a 1,4,5-trisubstituted benzene moiety [δH 6.56 (s) H-13; δ 6.92,
.86 (2H, both d, J = 8.2 Hz) H-16, H-17], and a 1,4-disubstituted benzene moiety [δ 7.43, 7.05
6
H
0
0
0
0
(2H, both d, J = 8.2 Hz) H-13 , H-14 ;
δ
6.76, 6.38 (2H, both d, J = 8.2 Hz) H-16 , H-17 ], together with
H
0
0
three aromatic proton singlets (
compound
δ
H
6.42, H-6;
δ
6.66, H-6 ;
δ
6.01, H-9 ) [21]. The NMR spectrum of
2.27, 2.62 (s) H-2, H-2 ] and four O-methyl signals
0
1
exhibited two N-methyl signals [
δ
H
0
δ 3.15, 3.37, 3.73, 3.89 (s) CH O-8, CH O-7 , CH O-7, CH O-15] (Supplementary Information
H 3 3 3 3
[
Figure S2). Furthermore, compound
1 is an isomer of well-known dauricine’s analogues [18–20].
The structure of dauricine was established as a head-to-tail BBIQA by spectroscopic data [21].

Molecules 2018, 23, 99
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However, the HMBC spectrum of
within the two tetrahydroisoquinoline units, but gave no additional information about the connectivity
of the two moieties (head-to-tail, tail-to-tail, or head to head; no correlations via four bonds were
1
showed the expected C
−
H correlations via two and three bonds
0
0
0
observed; SI Figure S9). In addition, H-11/11 correlated with the aromatic carbons C-10/10 , C13/13
0
and C17/17 (Supplementary Information Figure S9). Analysis of the ROESY spectrum suggested the
0
0
methoxy position to aromatic rings [correlations between H-6, CH O-7, and H-6 , CH O-7 , and H-16,
3
3
CH O-15, respectively; Supplementary Information Figure S10]. Collectively, these data indicate the
3
structure of the new compound Lunagrad A (1) as shown in Figure 1.
Lunagrad B (
which requires ten degrees of unsaturation, was determined on the basis of the [M + H] ion peak
at m/z = 541.1917 (calcd. 541.1921) in the HR-MS (ESI) . The acid hydrolysis of gave D-glucose,
which was identified after derivatization by GC-MS. The stereochemistry was determined by the
coupling constants of the anomeric hydrogen (7.2 Hz). The H and C-NMR (CD OD) spectra of
2) was obtained as a white amorphous powder. The molecular formula, C H O ,
25 32 13
+
2
β
1
13
2
3
(
Supplementary Information Figures S11 and S13), which were assigned by two-dimensional (2D)
gradient NMR experiments (HSQC, HMBC, COSY) (Supplementary Information Figures S14–S17),
showed benzyloxy protons [ 4.54 (2H, s) H-1], and two A B systems specific to a para-substituted
aromatic pattern [ 7.02, 7.27 (2H each, both d, J = 8.4 Hz) H-2 /6 , H-3 /5 ;
δ
2
0
2
0
0
0
δ
δ
00
6.69, 6.96 (2H each, both d,
0
0
00 00
J = 8.8 Hz) H-2 /6 , H-3 /5 ] (Supplementary Information Figure S14). In the HMBC experiment of
2
,
0
0
0
0
0
H-1 correlated with the aromatic C-1 and C-2 /6 (
δ
C
136.6, 129.5). The chemically equivalent H-2 /6
0 0
aromatic protons correlated with C-1 (δC 64.9), C-1 (δ 136.6) and the oxygenated C-4 (δ 158.5).
C C
0
0
00
In addition, the chemically equivalent H-2 /6 aromatic protons correlated with the oxygenated
C-1 /4 (
0
0
00
δ
152.5, 153.9) (Supplementary Information Figure S16). The HSQC spectrum clearly
C
showed two glucopyranosyl pattern and two correlation between the anomeric proton (
J = 7.2 Hz), H-4 -O-Glu-1 and H-4 -O-Glu-1] and the anomeric carbons (
δ
4.73) [(2H, d,
δ 102.4, 103.7) (Supplementary
C
0
00
Information Figure S15). On the basis of these findings, the structure of the new compound Lunagrad
B (2) was formulated as shown in Figure 3.
Figure 3. Key COSY (thick lines), HMBC (H→C) and ROESY (↔) correlations of 1 and 2.
3
. Experimental Section
3
.1. General
GC-MS and EIMS, Trace GS Ultra equipped with a capillary TR-5MS SQC column (0.25 µm,
1
5 m × 0.25 mm i.d.) and DSQII Thermo Scientific mass spectrometer. High resolution mass spectra
were measured at Keecloud Mass Spectrometry Service Company on a Thermo Scientific LTQ Orbitrap
XL system. Optical rotations were measured on a JASCO-1020 polarimeter (JASCO, Tokyo, Japan).
Infrared spectra were collected on a Bruker model TENSOR27 spectrophotometer (Bruker Optics,
Ettlingen, Germany). All of the NMR spectra were obtained using a Bruker AVANCE III 500 spectrometer
(Bruker BioSpin, Rheinstetten, Germany). Sephadex LH-20 (25–100
µm, Pharmacia Fine Chemical Co.,
Ltd., Uppsala, Sweden), D101/D201 macroporous adsorption resin (Dalian Elite Analytical Instrument

Molecules 2018, 23, 99
4 of 7
Co. Ltd., Dalian, China), MCI GEL CHP20P (Mitsubishi Chemical Co., Tokyo, Japan), C18 reversed-phase
silica gel (230–400 mesh, Sigma-Aldrich, St. Louis, MO, USA), Silica gel (200–300 mesh), and Silica
gel H (Qingdao Oceanic Chemical Co., Ltd., Qingdao, China) were used for column chromatography.
Thin-layer chromatography (TLC) was performed on glass-backed plates coated with 0.25 mm layers
of Silica gel H (Qingdao Oceanic Chemical Co., Qingdao, China). Fractions were monitored by TLC
and spots were visualized by heating silica gel plates sprayed with 5% H SO in EtOH/H O (1/1).
2
4
2
All of the solvents and chemicals that were used were of analytical reagent grade (Sinopharm Chemical
Reagent Co., Ltd., Beijing, China), and water was doubly distilled before use.
3
.2. Plant Material
Cymbidium Lunagrad Eternal Green was purchased from Fujian Flower Market, Fujian Province,
People’s Republic of China, in September 2012 and identified by Prof. Shi-Pin Chen, Forestry College,
Fujian Agriculture and Forestry University. A voucher specimen (No. 070612) was deposited in the
Forestry College, Fujian Agriculture and Forestry University.
3
.3. Extraction and Isolation
The flower organs of the plant (air-dried, 36 g) were extracted with MeOH (2 L, 3 d) at room
temperature for three times and the combined organic phase was concentrated in vacuum via a rotavap.
The residue was subjected to D101 macroporous adsorption resin and then filtered to give 9 g of crude
extract. The extract was subjected to D201 macroporous adsorption resin with a H O/MeOH elution
2
gradient (from 100% H O to 100% MeOH) to yield 10 fractions (Fractions 1–10).
2
Fraction 2 (608 mg) was subjected to silica gel column chromatography (CHCl /MeOH, 20:1) to
3
give 10 (18.7 mg, R = 0.20, CHCl /MeOH = 10:1).
f
3
Fraction 3 (1.30 g) was subjected to Sephadex LH-20 column chromatography eluted with MeOH
to afford four fractions 3-1–3-4. Fraction 3-1 was further purified by RPC column chromatography
(
(
MeOH/H O, 1:1) to afford
1
(60.7 mg). Fraction 3-3 was purified by MCI column chromatography
MeOH/H O, 3:5 to 1:0) to afford (20.3 mg). Fraction 3-4 was obtained as white powder (2, 26.4 mg)
in 2M hdrochloric acid (0.5 mL) was heated to reflux for 3 h. The solution was
2
6
.
2
A solution of
2
extracted with t-butyl alcohol. The dried residue of the aqueous layer was derivatized by pyridine and
◦
1
-(trimethylsilyl)-imidazole at 60 C for 1 h. The mixture was analyzed by GC-MS (Trace GS Ultra)
with a capillary TR-5MS SQC column (0.25
µ
m, 15 cm
×
0.25 mm) under the following conditions:
◦
◦
◦
1
min at 40 C, increase of temperature with a thermal ramp of 10 C/min until 250 C (helium flow
◦
◦
rate 1 mL/min, injector temperature 250 C, transfer temperature 285 C). Impact electronic detection
was performed with a DSQII Thermo Scientific mass spectrometer. Identification of D-glucose was
carried out by a comparison of its retention time and spectroscopic data with those of an authentic
sample of D-glucose (Purchased from Aldrich), t 14.8 min.
R
Fraction 4 (1.50 g) was subjected to D201 macroporous adsorption resin with a H O/MeOH
2
elution gradient (H O/MeOH, 9:1 to 1:4) to yield 6 fractions 4-1–4-6. Fraction 4-3 was obtained as
2
white powder (
ether/acetone, 10:1 to 1:1) to yield
Fraction 4-5 was purified by MCI column chromatography eluting with MeOH to afford 8 (12.6 mg).
Fraction 7 (1.20 g) was subjected to silica gel column chromatography (CHCl /MeOH, 30:1 to 3:1)
5
, 39.2 mg). Fraction 4-4 was subjected to silica gel column chromatography (petroleum
4
(23.2 mg, R = 0.26, CHCl /MeOH = 10:1) and (30.1 mg).
9
f
3
3
to yield 6 fractions 7-1–7-6. Fraction 7-2 was obtained as a white powder (3, 25.0 mg). Fraction 7-3 was
purified by MCI column chromatography (H O/MeOH, 2:3), to afford 7 (39.4 mg).
2
Fraction 8 (910 mg) was subjected to silica gel column chromatography (petroleum ether/acetone,
2
0:1 to 2:1) to yield 5 fractions 8-1–8-5. Fraction 8-5 was obtained as yellow powder (11, 19.6 mg).
3
.4. Spectral Data
2
5
Lunagrad A (
420, 1617, 1509, 1463, 1270, 1222, 1169, 1125, 1076 cm . HR-MS (ESI) m/z calculated for C H N O
7
1
). Slightly yellow, amorphous powder. [
α
]
+11.4 (c 0.1, MeOH). IR (KBr) νmax
D
−
1
3
38
45
2

Molecules 2018, 23, 99
5 of 7
+
1
13
[
M + H] 641.3227, found 641.3230. H-NMR (500 MHz, CD OD) and C-NMR (125 MHz, CD OD)
3
3
data (see Table 1).
Table 1. 1H-NMR (500 MHz) and 13C-NMR (125 MHz) data of compound
Supplementary Information Figures S2 and S3).
1
in CD OD (
δ, ppm; J, Hz)
3
(
No.
1H-NMR
13C-NMR
No.
1H-NMR
13C-NMR
0
0
1
2
CH
CH3
3.82, d, 10.0
2.27, s
63.0
43.1
1
2
CH
CH3
4.00, dd, 11.0, 6.0
64.5
42.5
2.62, s
3
2
2
.49, overlap
.91, overlap
.92, overlap
3.47, m
2.78, overlap
3.01, m
2.86, overlap
0
3
CH2
45.3
3
CH2
45.7
0
4
CH2
23.7
4
CH2
26.0
2
.53, dd, 14.5, 4.5
0
5
6
7
C
CH
C
CH3
C
CH3
C
C
-
124.0
107.3
153.0
56.4
139.3
60.7
5
6
7
C
CH
C
CH3
C
-
129.1
113.7
150.3
56.1
0
6.42, s
6.66, s
0
-
-
0
7
8
-OMe
8
-OMe
9
3.73, s
7 -OMe
3.37, s
0
-
8
-
-
145.2
3.15, s
0
-
-
149.4
129.3
9
CH
C
6.01, s
121.4
129.0
0
1
0
10
-
3.27, dd, 12.5, 6.0
2.87, overlap
-
2
.76, dd, 14.5, 10.0
2
0
1
1
CH2
42.6
11
CH2
37.5
.46, d, 14.5
0
12
13
14
15
C
CH
C
-
135.8
116.7
151.0
148.7
56.8
12
13
14
15
-
16
17
C
CH
CH
C
136.7
131.8
122.9
155.1
-
0
6.56, d, 1.6
7.43, d, 8.2
7.05, d, 8.2
-
0
-
-
0
C
1
5-OMe
CH3
CH
CH
3.89, s
6.92, d, 8.2
6.86, d, 8.2
-
-
0
0
1
1
6
7
113.2
124.4
CH
CH
6.76, d, 8.2
6.38, d, 8.2
122.8
133.9
2
5
Lunagrad B (
2
). White, amorphous powder. [
α
]
−
37.8 (c 0.1, MeOH). IR (KBr) νmax 3230,
D
−
1
+
1
610, 1450, 1221, 1188, 1095 cm . HR-MS (ESI) m/z calculated for C H O [M + H] 541.1921,
found 541.1917. H-NMR (500 MHz, CD OD) and C-NMR (125 MHz, CD OD) data (see Table 2).
25
33 13
1
13
3
3
Table 2. 1H-NMR (500 MHz) and 13C-NMR (125 MHz) data of compound
2
in CD OD (
δ, ppm; J, Hz)
3
(Supplementary Information Figures S11 and S12).
No.
1H-NMR
13C-NMR
No.
1H-NMR
13C-NMR
0
00
1
C
-
136.6
129.5
117.7
158.5
102.4
75.1
78.2
71.5
78.1
1
C
-
153.9
116.6
119.4
152.5
103.7
75.0
78.0
71.4
78.0
0
0
0
0
00 00
2
3
, 6
CH
CH
C
CH
CH
CH
CH
CH
7.27, d, 8.4
7.07, d, 8.4
-
4.89, d, 7.2
3.42, overlap
3.41, overlap
3.34, overlap
3.36, overlap
2 , 6
CH
CH
C
CH
CH
CH
CH
CH
6.69, d, 8.8
6.96, d, 8.8
-
4.73, d, 7.2
3.42, overlap
3.41, overlap
3.34, overlap
3.36, overlap
00 00
, 5
3 , 5
0
00
4
4
0
0
0
0
0
00
4
4
4
4
4
-O-Glu-1
-O-Glu-2
-O-Glu-3
-O-Glu-4
-O-Glu-5
4 -O-Glu-1
4 -O-Glu-2
4 -O-Glu-3
4 -O-Glu-4
00
00
00
00
4 -O-Glu-5
3
3
.88, br.d, 12.0
.69, br.d, 12.0
4.54, s
3.88, br.d, 12.0
3.69, br.d, 12.0
-
0
00
4
-O-Glu-6
1
CH2
CH2
62.6
64.9
4 -O-Glu-6
CH2
-
62.5
-
-
4
. Conclusions
The first chemical investigation of the flowers of Cymbidium Lunagrad Eternal Green resulted in the
isolation of a new alkaloid, named Lunagrad A ( ), and a new aromatic glucoside, named Lunagrad
B ( ), together with nine known compounds, 11. These specific compounds provided further
1
3–
2

Molecules 2018, 23, 99
6 of 7
confirmation of the typical profile of secondary metabolites that are found in the orchid family,
and might be useful for further biological studies.
Supplementary Materials: Copies of H, 13C, DEPT, COSY, HSQC, HMBC and ROESY spectra of new compounds.
1
This material is available free of charge online.
Acknowledgments: Financial support from the Guiding Project from Fujian Province (No. 2015N0020),
Natural Science Foundation of Fujian Province of China (No. 2016J05024), Fujian Agriculture and Forestry
University Foundation for Outstanding Youth (No. XJQ201623) is gratefully acknowledged.
Author Contributions: Ming-An Ouyang conceived and designed the experiments. Li-Yan Song, Fang Huang
and Yan Wang performed the experiments. Li-Yan Song, Zu-Jian Wu and Ming-An Ouyang analyzed the data.
Li-Yan Song composed the manuscript.
Conflicts of Interest: The authors declare no conflicts of interest.
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Sample Availability: Samples of all compounds in the manuscripts are available from the authors.
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