Chinese

Journal of
Natural
Chinese Journal of Natural Medicines 2009, 7(4): 270273 Medicines

Two New Terpenoids from Valeriana officinalis

ZHOU Ying, FANG Ying*, GONG Zhan-Feng, DUAN Xue-Yun, LIU Yan-Wen*
Hubei Key Laboratory of Resource Science and Chemistry in Chinese Medicine, Hubei College of Traditional Chinese Medicine, Wuhan
430061, China
Available online 20 July 2009

[ABSTRACT] AIM : To study the chemical constituents of the roots of Valeriana officinalis L. METHODS: Chemical constituents
were isolated by various column chromatographic techniques and their structures were elucidated by spectroscopic methods.
RESULTS: A new sesquiterpene, orivalerianol (4ȕ, 10Į, 15-trihydroxy-aromadrendane) (1), and a new iridoid, monovalerianester A
(aglycone of kanokoside A) (2) together with eight known compounds rulepidol (3), behenic acid (4), pinoresinol (5), valerenic acid
(6), ȕ-sitosterol (7) , kanokoside A (8), prinsepiol-4-O-ȕ-D-glucoside (9) and 8-hydroxypinoresinol-4-O-ȕ-D-glucoside (10) were
obtained from the EtOAc extract (1~6) and n-BuOH extract (7~10). CONCLUSION: Compounds 1 and 2 are new natural products.
[KEY WORDS] Valeriana officinalis; Orivalerianol; 4ȕ, 10Į, 15-Trihydroxy-aromadrendane; Monovalerianester A
[CLC Number] R284 [Document code] A [Article ID]1672-3651(2009)04-0270-04

1 Introduction  2 Results and Discussion

Valeriana officinalis (Valerianaceae) has widely distrib-
uted in the world. As a traditional herbal medicine, the roots
of Valeriana officinalis have long been used for sedative and
antispasmodic purposes[1-3]. Modern research shows that it
also can be used for curing cardiac arrhythmia[4]. In order to
explore how it works, we initiate a project to study the con-
stituents from it.
In our study, A new sesquiterpene,4ȕ,10Į,15-trihydroxy-
aromadrendane (1), and a iridoid, aglycone of kanokoside A
(2) together with eight known compounds rulepidol (3) , be-
henic acid[5] (4) , pinoresinol [6] (5), valerenic acid[7] (6),
ȕ-sitosterol[8] (7) , kanokoside A[9] (8) , prinsepiol-4-O-ȕ-D-
glucoside[10] (9) and 8-hydroxypinoresinol-4-O-ȕ-D- gluco-
side[11] (10) were obtained from the EtOAc extract (1-6) and
n-BuOH extract (7-10). In this paper, we mainly report the
isolation, and structural elucidation of the two new com-
pounds.
[Received on] 01-Feb-2009
[Foundation Item]This project was supported by the National
Natural Science Foundation of China (No. 30500053)
[
Corresponding author] FANG Ying: Assistant Researcher, Tel:
86-27-88920834, E-mail: fangyingchina@yahoo.com.cn
LIU Yan-Wen: Prof., Tel: 86-15327285560, E-mail:
ywliu2008@163.com
Copyright©2009, China Pharmaceutical University.
Published by Elsevier B.V. All rights reserved.
Compound 1 was obtained as amorphous powder. The
EI-MS gave a molecular ion peak at m/z 254.2 [M] +. Its mo-
lecular formula of C15H26O3 was established by its
HR-TOF-MS at m/z 277.177 2 [M + Na] + (calcd.277.1774)
and NMR spectra. The IR spectrum exhibited absorption
bands for -OH (3 385 cmҟ1). The13C NMR spectrum showed
fifteen carbon signals. The DEPT experiment suggested that
it has three methyls, five methenes, four methines, and three
quarternary carbons. In the 1H NMR spectrum, a broad
singlet at į 2.26 (3H, br.s) was assigned as the overlapped
signals of three active hydroxyl protons. Three singlets at į
1.05 (3 H, s), 1.03 (3 H, s), 1.19 (3 H, s) suggests that the
three isolated methyls are connected with saturate quaternary
carbons. Overall analysis of the NMR signals together with
the degrees of insaturation for compound 1, 1ed to the con-
clusion that this compound is a saturate one with 3 rings in its
structure; in more detail, one of the rings has the characteris-
tic pattern of cyclopropane, supported by the upfield proton
signals at į 0.40 and į 0.64 in the 1H NMR spectrum of 1.
The plane structure of the compound was further con-
firmed by the interpretation of its 2D NMR spectra. In
the1H-1H COSY spectrum, correlations were observed be-
tween H-3 and H-2, H-2 and H-1, H-1 and H-5. In the
HMBC, C-4 correlated with H-3, H-15, and H-5. All above
indicate the presence of a pent-dimensional ring. Moreover,
in the HMBC spectrum, 12-Me correlated with C-6 and C-11,
and 13-Me correlated with C-11 and C-7, which suggests that
the cyclopropane is located at C-6, and stabilized by C-7. The
remaining ring was then supposed to be a hept-dimensional
 ZHOU Ying, et al. /Chinese Journal of Natural Medicines 2009, 7(4): 270273

ring. 14-Me correlated with C-9, C-10 and C-1, which sug-
gests that 14-Me located at C-10. The three remaining hy-
droxyls thus were connected with C-10, C-4 and C-15, re-
spectively. Therefore, the plane structure with an aromoden-
dane skeleton and three hydroxyls was determined. The fu11
assignments for all the protons and carbons of the compound
were shown in Table 1.
ety(į C 171.9, 43.1, 25.5, 22.2, 22.3), ten carbon sig-
nals (įC89.0, 141.3, 111.4, 34.2, 58.4, 58.7, 79.2, 42.9, 62.7,
65.8) were displayed for the iridoid skeleton. In comparison
with kanokoside A [9], most 1H and 13C NMR spectral data of
2 (Table 2) were identical (iridoid skeleton and isovaleryl

Table 1 NMR Data of Compounds 1 in CDCl3a) (1H NMR

600 MHz, 13C NMR 150 MHz, J in Hz)
Position į13C į 1H
1 58.0 1.90 (1H, dd, J =16.8, 9.6 Hz)
2 24.4 1.72 (1H, m); 1.72(1H,m) Fig. 1 Key HMBC and NOESY of compounds 1
1.58 (1H, ddd, J =12,9,7.2 Hz);
3 36.8
1.75 (1H, m) Table 2 NMR Data of compounds 2 in CDCl3a) (1H NMR
4 82.6 600 MHz, 13C NMR 150 MHz, J in Hz)
5 48.0 1.26 (1H, t, J =9.6 Hz) Position į 13C į 1H
6 28.0 0.40 (1H, dd, J =11,9.6Hz)
1 89.0 6.36 (1H,br s)
7 26.7 0.64 (1H, ddd, J =11,9.6, 6 Hz)
3 141.3 6.37 (1H,br s)
0.86 (1H, dt, J =15,12 Hz);
8 19.9 4 111.4
1.85 (1H, dt, J =15,6 Hz)
9 44.3 1.52 (1H,t, J =12.6 Hz); 1.80 (1H , m) 5 34.2 3.07 (1H, dd, J=7.2,1.2Hz)
10 74.7 6 58.4 4.07 (1H, d, J=1.8 Hz)
11 19.8 7 58.7 3.47 (1H, d, J=1.8 Hz)
12 28.4 1.05 (3 H, s) 8 79.2
13 16.2 1.03 (3 H, s) 9 42.9 2.17(1H, dd, J=7.2,0.6 Hz)
14 20.4 1.19 (3 H,s), 3.80 (1H, d, J=11.4Hz),
10 62.7
3.69 (1H, d, J =11Hz); 3.77 (1H, d, J=11.4Hz)
15 67.3
3.58 (1H, d, J =11 Hz) 4.10 (1H, d, J=12.6Hz),
11 65.8
4,10,15-OH 2.26 (3H, br s) 4.08 (1H, d, J=12.6Hz)
a)
All assignments based on the extensive 1D and 2D NMR spectra OCOCH2CH(Me)2
(DEPT, 1H-1HCOSY, NOESY, HMQC, and HMBC). 171.9
2.21 (1H, d, J=6.6Hz),
43.1
According to biogenesis relations, H-6 and H-7 of the 2.18 (1H, d, J=6.6 Hz)
cyclopropane which are located at C-6 and C-7 are 25.5 2.13 (1H, m, J=6.6Hz)

ȕ-configuration. The coupling constants and NOESY spec- 22.2

0.93 (6H, d, J=6.6Hz)
trum disclosed the relative configurations of C-1, C-4, C-5, 22.3
C-6, C-7 and C-10 of the compound. NOE correlations were a)
All assignments based on the extensive 1D and 2D NMR spectra
observed between H-7 and H-5, H-6, 14-CH3, between (DEPT, 1H-1HCOSY, TOCSY, HMQC, and HMBC).
l4-CH3 and H-1, H-6, H-7, between H-1 and H-5. The above
evidence led to the establishment of the structure of com- 11
OR11

pound 1 as represented in Fig. 1. It is a new sesquiterpene, H

and named as orivalerianol (4ȕ, 10Į, 15-trihydroxy- aro- O 6 5

4
3
7
madrendane). 8
9
1 O

Compound 2 was obtained as amorphous powder. The HO

H
O CH 3

10 OR1
EI-MS gave a molecular ion peak at m/z 314.2 [M] +. Its OH CH3

molecular formula of C 15 H 26 O 3 was established by its Iv

HR-TOF-MS at m/z 337.126 0 [M+Na] + (calcd.337.125 8)
and NMR spectra. The IR spectrum exhibited absorption
bands for -OH (3 389 cmҟ1), C=O (1 737 cmҟ1), and C=C (1
676 cmҟ1). Analysis of the overall NMR spectral data (Table 2)
revealed the presence of an iridoid skeleton with ester units.
In addition to the signals attributable to an isovaleryl moi-
2 R1= Iv, R11=H 8 R1= Iv, R11=glc
Fig. 2 Structure of compound 2
group), while the only significant difference was the lack of
one sugar unit (at C-11). Furthermore, the HMBC correla-
tions between H-1 [įH 6.36 (1H, br s)] and the carbonyl car-
 ZHOU Ying, et al. /Chinese Journal of Natural Medicines 2009, 7(4): 270273
bon (įC 171.9) of isovaleryl, revealed an isovaleryl groups at
C-1.Thus the above evidence led to the establishment of the
structure of compound 2 as represented in Fig. 2. Compound
2 is the aglycone of kanokoside A. It’s a new iridoid, and
named as monovalerianester A.
3 Experimental
3.1 General Experimental Methods
EI-MS measurement was carried out on an VG ZAB-3F
mass spectrometer. 1D and 2D NMR spectra were recorded
on a Varian INOVA-600 MHz NMR spectrometer with TMS
as the internal standard. Column chromatography was per-
formed using Toyopearl HW-40, Sephadex LH-20 gel and
silica gel (Qingdao Marine Chemical Factory) as loading
agent. TLC was performed on silica gel (Qingdao Marine
Chemical Factory). All solvents were chemical or analytical
pure (Tianjin Chemical Works).
3.2 Plant material
The roots of Valeriana officinalis L.were bought from
Chinese Crude Drug Company of Hubei Province. The iden-
tification of the plant was performed by Dr.Wu He-zhen,
Hubei College of Traditional Chinese Medicine. A voucher
specimen was deposited at Hubei Key Laboratory of Re-
source Science and Chemistry in Chinese Medicine.
3.3 Extraction and Isolation
Air-dried and powdered roots of Valeriana officinalis L
(15 kg) were extracted by SFE to get oil, the remaining gruffs
(13 kg)then were extracted with 70% ethanol(percolate, 10
column volumes), and the solvent was evaporated under re-
duced pressure. The 70% ethanol extract was suspended in
H2O and partitioned successively with EtOAc and n-BuOH,
and then concentrated to afford extracts EtOAc and n-BuOH.
The EtOAc extract (255 g) was subjected to silica gel (2
kg) column chromatography, eluted with petroleum ether-
EtOAc (9:1), petroleum ether- EtOAc (8:2), petroleum ether-
EtOAc (7:3), petroleum ether- EtOAc (6:4), EtOAc, and fi-
nally acetone to give 40 fractions (A1-A40). Fraction A33 was
further separated by silica gel, using gradient of acetone in
petroleum ether and then purified by pressurized silica gel
column (petroleum ether- acetone 8:2) and Toyopearl HW-40
column (chloroform-methanol 1:1) to afford compounds 1
(0.5 g) and 2 (40 mg). With a series of chromatographic
techniques, compounds 3 (60 mg), 4 (50 mg), 5 (0.2 g), and 6
(0.1g) were obtained from fractions A30, 31, A11, A32 and A10,
11, respectively.
The n-BuOH extracts were subjected to silica gel (2kg)
column chromatography, eluted with CHCl3-MeOH (98:2),
CHCl3-MeOH (9:1), CHCl3-MeOH (8:2), CHCl3- MeOH
(7:3), CHCl3-MeOH (6:4) and MeOH. Compound 7 (50mg)
was crystallized from the CHCl3-MeOH (98:2) fraction.
Compound 8 (0.1g) was separated by silica gel columns and
Toyopearl HW-40 column (chloroform-methanol) chromato-
graphy from the CHCl3-MeOH (6:4) fraction. The CHCl3-
MeOH (7:3) fraction was respectively subjected to silica gel
columns and Sephadex LH-20 column(methanol) chroma-
tography, yielding compound 9 (50 mg) and 10 (20mg).
Acknowledgements
We appreciate the assistance from Li Qiao, Qiu
Wei-mao, Xiong Hui and Xiong Lei; we are also thankful to
Liu Hong-bing, for his help in the NMR measurement.
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