A new coumarin and a new norlignan from Ficus tsiangii

Article abstract of DOI:10.1080/10286020.2018.1426572

Chemical investigation of the stem bark of Ficus tsiangii led to the isolation of a new coumarin ficuscoumarin (1) and a new norlignan ficuslignan (2) by chromatographic methods. Their structures were elucidated on the basis of spectroscopic analyses.

Full text of DOI:10.1080/10286020.2018.1426572

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: http://www.tandfonline.com/loi/ganp20
A new coumarin and a new norlignan from Ficus
tsiangii
Song-Leng Duan, Jun Zhang, Qing-Hua Han, Qing-Ying Zhang & Hong Liang
To cite this article: Song-Leng Duan, Jun Zhang, Qing-Hua Han, Qing-Ying Zhang & Hong Liang
(2018): A new coumarin and a new norlignan from Ficus tsiangii, Journal of Asian Natural Products
Research, DOI: 10.1080/10286020.2018.1426572
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Journal of asian natural Products research, 2018
ꢁꢁpꢂ://ꢃꢄꢅ.ꢄꢆg/10.1080/10286020.2018.1426572
ꢀ
A new coumarin and a new norlignan from Ficus tsiangii
a,b
a
a
a
a
Song-Leng Duan , Jun Zhang , Qing-Hua Han , Qing-Ying Zhang and Hong Liang
ꢇ
sꢁꢇꢁꢈ Kꢈy lꢇbꢄꢆꢇꢁꢄꢆy ꢄꢉ nꢇꢁꢊꢆꢇꢋ ꢇꢌꢃ Bꢅꢄmꢅmꢈꢁꢅꢍ dꢆꢊgꢂ, sꢍꢀꢄꢄꢋ ꢄꢉ Pꢀꢇꢆmꢇꢍꢈꢊꢁꢅꢍꢇꢋ sꢍꢅꢈꢌꢍꢈꢂ, Pꢈkꢅꢌg uꢌꢅvꢈꢆꢂꢅꢁy,
b
Bꢈꢅjꢅꢌg 100191, cꢀꢅꢌꢇ; Bꢈꢅjꢅꢌg sꢀꢅjꢅꢁꢇꢌ hꢄꢂpꢅꢁꢇꢋ, cꢇpꢅꢁꢇꢋ Mꢈꢃꢅꢍꢇꢋ uꢌꢅvꢈꢆꢂꢅꢁy, Bꢈꢅjꢅꢌg 100038, cꢀꢅꢌꢇ
ABSTRACT
ARTICLE HISTORY
Chemical investigation of the stem bark of Ficus tsiangii led to the
isolation of a new coumarin ficuscoumarin (1) and a new norlignan
ficuslignan (2) by chromatographic methods. Their structures were
elucidated on the basis of spectroscopic analyses.
rꢈꢍꢈꢅvꢈꢃ 20 nꢄvꢈmbꢈꢆ 2017
aꢍꢍꢈpꢁꢈꢃ 7 Jꢇꢌꢊꢇꢆy 2018
KEYWORDS
Mꢄꢆꢇꢍꢈꢇꢈ; Ficus tsiangii;
fiꢍꢊꢂꢍꢄꢊmꢇꢆꢅꢌ; fiꢍꢊꢂꢋꢅgꢌꢇꢌ
CH OH
2
HOH C
2
OCH
3
HO
HOH C
O
O
Oglc
2
HO
OCH3
1
2
1
. Introduction

e genus Ficus of the plant family Moraceae is represented by about 1000 species mainly
distributed in tropics and subtropics in the world, and 98 species are found from the south-
west to the east and the south of China [1]. Ficus tsiangii Merr. ex Corner is shrubs or trees
growing in valleys up to altitudes between 200 and 2400 m, largely distributed in Guangxi,
Guizhou, Hubei, Hunan, Sichuan, and Yunnan provinces in China [2]. F. tsiangii is used
to treat cardiovascular diseases, especially as antithrombotic agent in some civil areas of
Sichuan province. Previous phytochemical and biological investigations on F. tsiangii indi-
cated the presence of triterpenes, flavonoids, coumarins, lignans, and fatty acids [3–8]. is
work deals with the isolation and structural elucidation of a new coumarin ficuscoumarin
(1) and a new norlignan ficuslignan (2) (Figure 1) from the stem bark of F. tsiangii.
CONTACT hꢄꢌg lꢅꢇꢌg
ꢋꢅꢇꢌgꢀꢄꢌg@bjmꢊ.ꢈꢃꢊ.ꢍꢌ
©
2018 iꢌꢉꢄꢆmꢇ uK lꢅmꢅꢁꢈꢃ, ꢁꢆꢇꢃꢅꢌg ꢇꢂ tꢇyꢋꢄꢆ & fꢆꢇꢌꢍꢅꢂ Gꢆꢄꢊp

2
S.ꢀL. DUAN ET AL.
7
' CH OH
2
1'
2
3'
'
9
5'
OCH
HOH C
2
3
8
4'
HO
HOH C
O
O
1
Oglc
7
2
HO 4
3
OCH
3
1
2
Figure 1. sꢁꢆꢊꢍꢁꢊꢆꢈꢂ ꢄꢉ ꢍꢄmpꢄꢊꢌꢃꢂ 1 ꢇꢌꢃ 2.
2
. Results and discussion

e EtOAc soluble part of the ethanol extract of F. tsiangii was subjected to silica gel and
Sephadex LH-20 column chromatography to afford compound 1, and the BuOH soluble
part was subjected to HP-20 column chromatography and C18 column chromatography
to afford compound 2.
Compound 1 was obtained as amorphous powder, with a molecular formula C H O
1
0
8
4
−
1
established by negative HRESI-MS at m/z 191.0344 [M − H] . e H NMR spectrum gave
two ortho-coupled proton signals at δ 6.18 (1H, d, J = 9.3 Hz) and 7.99 (1H, d, J = 9.3 Hz),
two aromatic proton signals at δ 7.59 (1H, s) and 6.71 (1H, s), and aliphatic proton signal
at δ 4.48 (2H, s), displaying the presence of hydroxymethyl group. e C NMR spectrum
showed eight aromatic or olefinic carbon signals (δ 101.3–158.1), one carbonyl carbon
1
3
1
13
signal (δ 160.6), and one aliphatic carbon signal (δ 57.5). e H NMR and C NMR data
Table 1) of 1 suggested that 1 was a coumarin [9]. In the NOESY experiment (Figure 2),
(
the aliphatic proton signal at δ 4.48 (2H, s) correlated with the downfield aromatic proton
signal at δ 7.59, indicating that the hydroxymethyl group was attached to C-6. e structure
of 1 was elucidated as 7-hydroxy-6-hydroxymethylcoumarin, named ficuscoumarin.
Compound 2 was obtained as amorphous powder and its molecular formula was deter-
1
3
mined to be C H O from the C NMR data and the negative HRESI-MS at m/z 495.1870
24
32 11
−
−
1
[
M − H] and 541.1924 [M + HCOO] . e H NMR spectrum of 2 (Table 2) revealed an
ABX system aromatic ring [δ 6.64 (1H, d, J = 1.6 Hz, H-2), 6.55 (1H, d, J = 8.0 Hz, H-5),
6
.46 (1H, dd, J = 8.0, 1.6 Hz, H-6)] and a 1,3,4,5-tetrasubstituted aromatic ring [δ 6.83 (1H,
1
brs, H-2′) and 6.82 (1H, brs, H-6′)] in the downfield region. e H NMR spectrum revealed
two methoxy groups at δ 3.74 (3H, s, 5′-OCH ) and 3.65 (3H, s, 3-OCH ), and a sugar
3
3
Table 1. h- ꢇꢌꢃ 13c-nMr ꢂpꢈꢍꢁꢆꢇꢋ ꢃꢇꢁꢇ ꢄꢉ 1 (dMso-d6).
1
No.
δH (m, J Hz)
δC
2
3
4
160.6
110.8
144.8
111.2
126.9
126.6
158.1
101.3
154.1
57.5
6.18(ꢃ,9.3)
7.99(ꢃ,9.3)
4
5
6
7
8
8
ꢇ
7.59(ꢂ)
6.71(ꢂ)
4.48(ꢂ)
ꢇ
ch oh
2

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
HO
HOH C
O
H
O
2
H
Figure 2. Kꢈy noesY ꢍꢄꢆꢆꢈꢋꢇꢁꢅꢄꢌꢂ ꢄꢉ 1.
Table 2. h- ꢇꢌꢃ 13c-nMr ꢂpꢈꢍꢁꢆꢇꢋ ꢃꢇꢁꢇ ꢄꢉ 2 (dMso-d6).
1
No.
δH (m, J Hz)
δC
HMBC
1
2
3
4
5
6
7
131.5
112.6
147.0
144.2
114.9
120.8
37.5
6.64(ꢃ,1.6)
c-1/c-3/ c-4/c-6/c-7
6.55(ꢃ,8.0)
6.46(ꢃꢃ,8.0,1.6)
2.90(ꢃꢃ,6.0,14.0)
c-1/c-3/c-4
c-2/c-4/ c-7
2
.62(ꢃꢃ,8.8, 14.0)
c-1/c-2/c-6/c-8/c-9/c-3′
c-7/c-2′/c-3′
8
9
3.78–3.83(m)
40.6
64.8
3.43–3.47(m), 3.62(ꢃꢃ,3.2,9.6)
1
2
3
4
5
6
7
1
2
3
4
5
6
′
′
′
′
′
′
′
″
″
″
″
″
″
138.5
117.1
137.7
151.4
142.1
108.9
63.0
103.7
74.4
76.4
69.6
76.7
60.9
55.8
6.83(bꢆ ꢂ)
c-8/c-4′/ c-6′/ c-7′
6.82(bꢆ ꢂ)
4.42(ꢂ)
4.62(ꢃ,7.2)
c-2′/c-4′/ c-5′/c-7′
c-1′/c-2′/c-6′
c-4′
3.23–3.28(m)
3.19–3.23(m)
3.13–3.18(m)
2.97–3.01(m)
3.57–3.60(m), 3.44–3.47(m)
3.74(ꢂ)
c-1″/c-3″
c-4″
c-5″
c-3″
och3–5
′
c-5′
och3–3
3.65(ꢂ)
55.3
c-3
1
anomeric proton at δ 4.62 (1H, d, J = 7.2 Hz, H-1″). Additionally, the H NMR spectrum
revealed two oxygenated methylenes at δ 4.42 (2H, s, H-7′), 3.62 (1H, dd, J = 3.2, 9.6 Hz,
H-9), and 3.43–3.47 (1H, m, H-9), one methine proton at δ 3.78–3.83 (1H, m, H-8), and
one methylene proton at δ 2.90 (1H, dd, J = 6.0, 14.0 Hz, H-7) and 2.62 (1H, dd, J = 8.8,
1
3
1
4.0 Hz, H-7). e C NMR spectrum of 2 (Table 2) revealed the presence of 24 carbon
atoms, of which six carbons could be assigned to a sugar moiety (δ 103.7, 76.7, 76.4, 74.4,
9.6, 60.9), two methoxy groups (δ 55.8, 55.3), and the remaining 16 carbons could be
6
assigned to a norlignan skeleton (including 12 aromatic carbons, two oxygenated methylenes
at δ 64.8 and 63.0, one methylene at δ 37.5, and one methine at δ 40.6). Acid hydrolysis
of 2 gave an aglycone 2a and a sugar moiety, which was identified as D-glucose by HPLC
analysis of its arylthiocarbamate derivative with an authentic sample [10]. e structure of
2
was determined on the basis of HMBC experiment (Figure 3). In the HMBC spectrum,
H-6 at δ 6.46 correlated with C-2 at δ 112.6, C-4 at δ 144.2, and C-7 at δ 37.5, H-5 at
H
C
C
H
δ 6.55 correlated with C-3 at δ 147.0, C-4 at δ 144.2, and C-1 at δ 131.5, CH O-3 at δ
H
C
C
C
3
H
3
.65 correlated with C-3 at δ 147.0, indicating that the methoxy and the hydroxy group
C
were attached to C-3 and C-4, respectively. HMBC spectrum also displayed correlations
between H-6′ at δ 6.82 and C-2′ at δ 117.1, C-4′ at δ 151.4, C-5′ at δ 142.1, and C-7′ at
H
C
C
C

4
S.ꢀL. DUAN ET AL.
CH OH
2
H
H
H
HOH C
2
H
OCH
3
H
O
HO
OCH3
OH
O
HO
HO
OH
H
Figure 3. Kꢈy hMBc ꢍꢄꢆꢆꢈꢋꢇꢁꢅꢄꢌꢂ ꢄꢉ 2.
δ 63.0, H-2′ at δ 6.83 and C-4′ at δ 151.4, C-6′ at δ 108.9, C-7′ at δ 63.0, and C-8 at δ
C
C
H
C
C
C
4
0.6, H-7′ at δ 4.42 and C-1′ at δ 138.5, C-2′ at δ 117.1, and C-6′ at δ 108.9, CH O-5′
H C C C 3
at δ 3.74 and C-5′ at δ 142.1, H-1″ at δ 4.62 and C-4′ at δ 151.4, indicating that the
H
C
H
C
methoxy and the glucosyl group were attached to C-5′ and C-4′, respectively. e HMBC
spectrum showed the correlations between H-7 at δ 2.90, 2.62 and C-3′ at δ 137.7, H-2′ at
H
C
δ 6.83 and C-8 at δ 40.6, indicating that C-8 was linked to C-3′. In addition, the absolute
H
C
configuration of C-8 in 2a was deduced to be R by comparison of its optical rotation data
25
[
ꢀ] -236 (c 0.2, MeOH) with those reported in the literature [11]. us, the structure of 2
d
was elucidated to be as shown in Figure 1 and was named ficuslignan.
3
. Experimental
3
.1. General experimental procedures
Optical rotations were obtained on a Rudolph Autopol IV automatic polarimeter (Rudolph
Research Analytical, New Jersey, USA). UV spectra were recorded on a Shimadzu UV–2450
UV–vis spectrophotometer (Shimadzu, Kyoto, Japan). IR spectra were taken on a ermo
Nicolet Nexus 470 FT-IR spectrometer (ermo Nicolet, Austin, TX, USA). NMR spectra
were measured on Bruker VXR-300 and AVANCE III-400 spectrometer (Bruker, Fällanden,
Switzerland) with tetramethylsilane as an internal standard. High-resolution electro-spray
ionization mass spectrometry (HRESI-MS) was obtained on a Waters Xevo G2 Q-TOF/
YCA mass spectrometer (Waters Corporation, Manchester, UK).
Column chromatography (CC) was performed on Diaion HP-20 (200–300 mesh,
Mitsubishi Chemical Co., Kyoto, Japan), silica gel (200–300 mesh; Qingdao Marine Chemical
Co. Ltd., Qingdao, China), Sephadex LH-20 (GE Healthcare, Uppsala, Sweden), ODS-A
(
50 μm, YMC Co. Ltd., Kyoto, Japan). Analytical TLC was carried out on silica gel GF254
10–40 μm; Qingdao Marine Chemical Co. Ltd., Qingdao, China). HPLC grade solvents
(
used for HPLC analysis were purchased from Fisher Scientific International (Fair Lawn,
New Jersey, USA), and deionized water was purified by Milli-Q Synthesis A10 (Bedford,
MA, USA). Other solvents used for extraction and isolation were of analytical grade and
purchased from Beijing Tongguang Chemicals (Beijing, China). All other chemicals were
purchased from J & K Co. Ltd. (Beijing, China).

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
3
.2. Plant material

e stem bark of Ficus tsiangii Merr. ex Corner was collected from Chongqing of China,
in April 2006. A voucher specimen (No. 200604001) was identified by Prof. Sirong Yi
(Chongqing Institute of Medicinal Plant Cultivation, Sanquan Zhen, Nanchuan District,
Chongqing 408435, China) and deposited in the Herbarium of Department of Natural
Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center
(PEM).
3
.3. Extraction and isolation
Air-dried powder of the bark of F. tsiangii (10.0 kg) was percolated with 95% EtOH (100
L) and 50% EtOH (100 L), successively. e combined extract was suspended in H O and
2
partitioned with EtOAc and n-BuOH, successively. e EtOAc soluble fraction (140.0 g) was
subjected to silica gel column, eluted gradiently with petroleum ether-acetone (9:1 → 1:1)
to give 18 fractions (E1–E18). Fr. E9 (1.47 g) was subjected to Sephadex LH-20 column,
eluted with MeOH-H O (8:2) and then separated by preparative TLC, developed with
2
CHCl -MeOH-HCOOH (15:1:0.1) to yield 1 (9.0 mg). e BuOH soluble fraction (75.0 g)
3
was subjected to HP-20 column, eluted with H O, 30% EtOH, 50% EtOH, 70% EtOH, and
2
9
5% EtOH, successively. e 30% EtOH eluate (7.0 g) was subjected to C18 column, eluted
with MeCN-H O (15:85) to yield 2 (3.0 mg).
2
3
.4. Acid hydrolysis and determination of the absolute configuration of the sugar
Compound 2 (2.0 mg) was dissolved in 2 M HCl–H O (2.0 ml) and heated at 95 °C for 8 h.
2

e mixture was extracted with EtOAc (2.0 ml) to give an aglycone 2a, and the aqueous layer
was evaporated under vacuum to furnish a neutral residue. L-Cysteine methyl ester hydro-
chloride (2.0 mg) and anhydrous pyridine (1.0 ml) were added to the mixture and stirred at
6
0 °C for 1 h. e product was mixed with O-tolylisothiocyanate (10 μl) and kept at 60 °C
for 1 h. e reaction mixture was analyzed by HPLC under the following conditions: an
Agilent 1260 chromatograph equipped with a phenomenex column (5 μm，4.6 × 250 mm);
column temperature: 35 °C; mobile phase: isocratic elution of 25% CH CN–H O containing
3
2
0
.2% formic acid for 50 min and subsequent washing of the column with 90% CH CN–H O,
3 2
flow rate: 0.8 ml/min; injection volume: 10 μl; UV detection wavelength: 250 nm. From the
acid hydrolysate of 2, D-glucose was confirmed by comparison of the retention time of its
derivative with the standard sugar D-glucose derivatized in the same way, which showed
retention time of 18.75 min.
3
.4.1. Ficuscoumarin (1)
Amorphous powder. UV (MeOH) λmax (lg ε) 204 (3.98), 220 (3.60), 328 (3.52) nm. IR
−
1 1
(
KBr) νmax 3444, 3361, 2921, 1740, 1601, 1498, 1260, 1023, 904, 801, 691, 586 cm . H
1
3
NMR (300 MHz, DMSO-d ) and C NMR (75 MHz, DMSO-d ) spectral data see Table 1.
6
6
−
HRESI-MS (negative mode) m/z 191.0344 [M − H] (calcd for C H O , 191.0344).
1
0
8
4

6
S.ꢀL. DUAN ET AL.
3
.4.2. Ficuslignan (2) 20
Amorphous powder.[ꢀ]D -134 (c 0.1, MeOH). UV (MeOH) λmax (lg ε) 205 (4.62), 225 (4.14),
2
1
75 (3.69) nm. IR (KBr) ν 3431, 3357, 3034, 1706, 1621, 1601, 1498, 1363, 1262, 1226,
max
−1
1
13
025, 752, 692, 581, 504 cm . H NMR (400 MHz, DMSO-d ) and C NMR (100 MHz−,
6
DMSO-d ) spectral data see Table 2. HRESI-MS (negative mode): m/z 495.1870 [M − H]
6
−
(calcd for C H O , 495.1866) and 541.1924 [M + HCOO] (calcd for C H O , 541.1921).
24
31 11
25 33 13
25
2
a[ꢀ] -236 (c 0.2, MeOH).
D
Acknowledgments

e authors expressed their thanks to Prof. Sirong Yi (Chongqing Institute of Medicinal Plant
Cultivation, Sanquan Zhen, Nanchuan District, Chongqing 408435, China) for his help in collection
of plant material and authentication.
Disclosure statement
No potential conflict of interest was reported by the authors.
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