Chemical Constituents from the Roots of
Hydrangea chinensis
Yue-Han Lee1(李岳翰), Fang-Rong Chang1 (張芳榮),
Ramesh Patnam1, Yuh-Chwen Chang1,2 (張裕純) , YangChang Wu1,* (吳永昌)
1Graduate
Institute of Natural Products, Kaohsiung Medical University
2Department of Chemical Engineering, Kao Yuan Institute of Technology
Abstract
Hydrangea chinensis (Saxifragaceae) is distributed in southern China, Ryukyu and
Taiwan at low altitude islandwide. Its roots were used as a traditional chinese medicine for
diuretic, anti-malaria and anti-headache agents.
In previous study, bergenin、phyllodulcin、hydrangenol and febrifugine were isolated
from the roots of Hydrangea genus. As our investigation of the phytochemical and
bioactive components from the roots of Hydrangea chinensis, the roots of this species
were extracted with MeOH at room temperature. The crude MeOH extract was
subsequently partitioned by n-Hexane/H2O, EtOAc/H2O, and n-BuOH/H2O, respectively.
One novel alkaloid, hydrachine A (1), along with five known compounds, 3H-quinazolin4-one (2), triacetyl glyceride (3), β-sitosterol-D-glucoside ester (4), β-sitosterol-Dglucoside (5), and glucose (6) were isolated from the n-BuOH layer. Fourteen known
compoumds, boarborinal (7), rubiarbonol B (8), β-sitosterol (9), 6-hydroxy-coumarin (10),
7-hydroxy-coumarin (11), 7-methoxy-coumarin (12), 7-hydroxy-8-methoxy-coumarin
(13), syringaldehyde (14), hydrangenol (15), hydrangenoside A (16), 4-hydroxy-transcinnamic acid methyl ester (17), p-coumarsaeuremethylester (18), triester glyceride (19),
and p-anisaldehyde (20) were isolated from the EtOAc layer, The structural elucidation of
these compounds was determined by spectroscopic analyses and their cytotoxicity are
under investigation.
O
O
N
H
N
N
OAc
NH
OH
OAc
O
N
OAc
Hydrachine A (1)
Triacetyl glyceride (3)
n=16
( )n
O
3H-Quinazolin-4-one (2)
O
HO
HO
O
O
OH
GlcO
17
b-Sitosterol-D-glucoside ester (4)
b-Sitosterol-D-glucoside (5)
HO
HO
O OH
OH
OH
HO
HO
OH
OH
Glucose (6)
Boarborinal (7)
Rubiarbonol B (8)
HO
O
HO
HO
O
O
O
4
b-Sitosterol
b-sitosterol (9)
6-Hydroxy-coumarin (10)
7-Hydroxy-coumarin (11)
HO
O
MeO
O
O
OMe
7-Methoxy-coumarin (12)
H
O
7-Hydroxy-8-methoxy-coumarin (13)
O
OH
HO
H
O
O
H
MeO
Syringaldehyde (14)
H
COOMe
O
OMe
OH
O
O
OH
O
Hydrangenol (15)
H
OGlu
Hydrangenoside A (16)
COOMe
HO
HO
COOMe
4-Hydroxy-trans-cinnamic acid methyl ester (17)
p-Coumarsaeuremethylester (18)
o
n
o
o
o
O
m
o
MeO
o
H
o
2
Triester
(19)
Triesterglyceride
Glyceride
p-Anisaldehyde (20)
Roots of Hydrangea chinensis (2 kg)
Extracted with Methanol
Crude Methanol Extracts (150 g)
Partition Procedure
n-Hexane
Ethyl acetate
n-Butanol
19.5 g
20.0 g
70.5 g
(83 % inhibition at the
Boarborinal (7)
concentration of 50µg/ml)
Rubiarbonol B (8)
b-sitosterol (9)
Hydrachine A (1)
6-Hydroxy-coumarin (10)
3H-Quinazolin-4-one (2)
7-Hydroxy-coumarin (11)
Triacetyl glyceride (3)
7-Methoxy-coumarin (12)
b-Sitosterol-D-glucoside ester (4)
7-Hydroxy-8-methoxy-coumarin (13)
b-Sitosterol-D-glucoside (5)
Syringaldehyde (14)
Glucose (6)
Hydrangenol (15)
Hydrangenoside A (16)
4-Hydroxy-trans-cinnamic acid methyl ester (17)
p-Coumarsaeuremethylester (18)
Triester glyceride (19)
p-Anisaldehyde (20)
Hydrachine A (1)
O
2'
(3-[9b-hydroxy-2-oxo-4-quinolizidyl]-4-quinazolinone)
6
7
3'
O
5
4a 4
N3
8a N
1
2
4'
1'
5'
H
N 10'
9'
6'
8'
•Semi solid
8
7'
1
25
• [] D +25.32 (c 0.2, CHCl3)
• UV (MeOH) max (log ) 224 (1.47), 230 (1.35), 233 (1.30), 265 (0.59), and 302 (0.28) nm
• IR (KBr) max 3600, 2700-2800, 1730, and 1670 cm-1
•EIMS m/z 314 [M+1]+ (7), 199 (3), 171 (31), 168 (31), 167 (96), 166 (84), 149 (42), 139
(25), 122 (25), 111 (24), 110 (100), and 103 (26)
• FABMS m/z 314 [M+1]+ (39), 312 (17), 304 (27), 284 (35), 282 (58), 256 (13), 168 (47),
167 (28), 147 (28), and 133 (49)
• HREIMS m/z 313.1420 (calcd for C17H19N3O3, 313.1426).
OH
Table 1. 1H-NMR and 13C-NMR data of Hydrachine A
δHa)(J Hz)
7.88 (1H, s)
NO.
2
4
4a
5
6
7
8
8a
1'pseudoeq
1'pseudoaxi
2'
3'pseudoeq
3'pseudoaxi
4'
6'eq
6'axi
7'eq
7'axi
8'eq
8'axi
9'
10'
OH
a) 1H-NMR
8.28 (1H, dd, J = 8.0, 1.6 Hz)
7.50 (1H, ddd, J = 8.0, 7.2, 1.6 Hz)
7.80 (1H, ddd, J = 8.4, 7.2, 1.6 Hz)
7.71 (1H, dd, J = 8.4, 1.6 Hz)
3.18 (1H, dd, J = 15.2, 3.2 Hz)
2.50 (1H, dd, J = 15.2, 11.2 Hz)
3.34 (1H, dd, J = 10.4, 6.4 Hz)
2.84 (1H, dd, J = 11.2, 10.4 Hz)
5.70 (1H, dd, J = 11.2, 6.40 Hz)
2.18 (1H, br. dt, J = 13.0, 4.0 Hz)
2.93 (1H, br. dd, J = 13.0, 4.0 Hz)
1.74 (1H, m)
1.80 (1H, m)
2.07 (1H, m)
1.29 (1H, m)
3.46 (1H, ddd, J = 11.0, 9.0, 5.0 Hz)
2.28 (1H, ddd, J = 11.2, 9.0, 3.2 Hz)
1.93 (1H, brs)
(400 MHz, CDCl3)
b) 13C-NMR
(100 MHz, CDCl3)
δC b)
145.1
160.5
121.7
126.9
127.5
134.6
127.3
147.5
43.8
43.8
201.6
59.0
59.0
59.4
54.1
54.1
23.0
23.0
32.8
32.8
72.9
67.1
Table 2. Structures and bioassay data of compounds
(Inhibition percentage at the concentration, 50µg/ml)
cell lines HONE-1 †
compounds
NUGC ‡
O
O
H
N
Hydrachine A (1)
N
OH
*
0%
0%
8%
1%
12%
0%
21%
21%
N
N
NH
3H-Quinazolin-4-one (2)
O
OAc
OAc
Triacetyl glyceride (3)
( )n
O
OAc
n=16
O
HO
HO
O
O
OH
b-Sitosterol-D-glucoside
ester (4)
17
* New compound
†HONE-1:human nasopharyngeal carcinoma
‡ NUGC: human gastric cancer
Positive compounds: % of control >50%
cell lines
compounds
Boarborinal (7)
HONE-1†
NUGC ‡
16%
0%
11%
7%
13%
4%
0%
2%
HO
HO
HO
OH
Rubiarbonol B (8)
b-Sitosterol (9)
HO
HO
4
b-Sitosterol
O
6-Hydroxy-coumarin (10)
O
cell lines
compounds
HO
HONE-1 †
NUGC ‡
10%
29%
O
O
O
O
18%
19%
O
O
4%
3%
7%
6%
7-Hydroxy-coumarin (11)
MeO
7-Methoxy-coumarin (12)
HO
OMe
7-Hydroxy-8-methoxy-coumarin (13)
H
O
MeO
Syringaldehyde (14)
OMe
OH
References and Notes
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2.
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4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
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