In continuous research on the chemical constituents of the twigs and leaves of Fokienia hodginsii (Dunn) A. Henry et Thomas growing in Highland, Lam Dong province 4 diterpenoids, including 3-oxo-totarol (totarolone, 1), 3β-hydroxytotarol (2), 15-nor-labda-8(17),12E-diene-14-carboxaldehyde-19-oic acid (3) and 13-oxo-15,16-dinorlabda-8(17),11E-diene-19-oic acid (4) were isolated. Their structures were elucidated by the spectroscopic methods and comparison with reported data. This is the first report on the isolation of compounds 1, 2 and 3 from this plant. Keywords. Fokienia hodginsii; totarane; nor-labdane diterpenoid

Hau, Dang Viet

Hong Nhung, Le Thi

Loc, Tran Van

Quan, Tran Duc

Sung, Tran Van

Tam, Nguyen Thanh

Thien, Dao Duc

Thuy, Trinh Thi

Tinh, Bui Xuan

Vietnam Academy of Science and Technology: Journals Online

  
Vietnam Journal of Chemistry, International Edition, 55(5): 557-560, 2017 
DOI: 10.15625/2525-2321.2017-00507 
557 
 
 
 
Diterpenoids from Fokienia hodginsii 
Dang Viet Hau
1,2
, Nguyen Thanh Tam
1,2
, Tran Duc Quan
1
, Dao Duc Thien
1
, Bui Xuan Tinh
3
,  
Le Thi Hong Nhung
4
, Tran Van Loc
1
, Tran Van Sung
1
, Trinh Thi Thuy
1,2* 
1
Institute of Chemistry, Vietnam Academy of Science and Technology 
2
Graduate University of Science and Technology, Vietnam Academy of Science and Technology 
3
Quang Trung University 
4
Hanoi University of Industry    
Received 27 July 2017; Accepted for publication 28 August 2017 
 
Abstract 
In continuous research on the chemical constituents of the twigs and leaves of Fokienia hodginsii (Dunn) A. Henry 
et Thomas growing in Highland, Lam Dong province 4 diterpenoids, including 3-oxo-totarol (totarolone, 1), 3β-
hydroxytotarol (2), 15-nor-labda-8(17),12E-diene-14-carboxaldehyde-19-oic acid (3) and 13-oxo-15,16-dinorlabda-
8(17),11E-diene-19-oic acid (4) were isolated. Their structures were elucidated by the spectroscopic methods and 
comparison with reported data. This is the first report on the isolation of compounds 1, 2 and 3 from this plant.  
Keywords. Fokienia hodginsii; totarane; nor-labdane diterpenoid.  
 
1. INTRODUCTION 
 
Fokienia hodginsii (Dunn) A. Henry et Thomas 
(synonym Cupressus hodginsii Dunn)-“local name 
Pơ mu”- belongs to family Cupressaceae. It is a big 
tree, 20-30 m tall, mainly distributed in China and 
Vietnam [1]. Po mu tree is known for its beauty, 
fragrance and high-value wood. Previous 
investigations of this plant have been mainly focused 
on the chemical composition of the essential oil [2]. 
Hitherto, there is only one report on the chemical 
constituents of this species growing in China. Its 
main components included diterpenoids: 
isopimarane, labdane, and icetexane [2]. In our 
previous chemical investigation, from the ethyl 
acetate extract of twigs and leaves of this 
plant growing in Highland, Lam Dong province there 
yielded two megastigmanes, namely drummondol 
and vomivoliol [3]. In our continued work on the 
hexane extract of this plant, 4 diterpenoids as 3-oxo-
totarol (totarolone, 1), 3β-hydroxytotarol (2), 15-nor-
labda-8(17),11E-diene-14-carboxaldehyde-19-oic 
acid (3) and 13-oxo-15,16-dinor-labda-8(17),11E-
diene-19-oic acid (4) were isolated and structurally 
determined.  
2. EXPERIMENTAL 
 
2.1. General 
1
H-NMR (500 MHz) and 
13
C-NMR (125 MHz) were 
taken on a Bruker Avance AM500 spectrometer 
using TMS as internal standard for 
1
H and solvent 
signal for 
13
C. ESI-MS was taken on an Agilent 1100 
LC-MSD Trap spectrometer. TLC aluminum sheets 
of silica gel Merck 60 F254 (layer thickness 0.2 mm) 
were used. Column chromatography (CC) was 
carried out on silica gel Merck 60 (0.040-0.063 mm) 
and Sephadex LH-20. 
 
2.2. Plant Material 
 
F. hodginsii was collected in Highland, Lam Dong 
province, Vietnam in August, 2012 and identified by 
Dr. Nguyen Tien Hiep. A voucher specimen (No. 
VNMN. B000005002) is deposited in the Vietnam 
National Museum of Nature, Vietnam Academy of 
Science and Technology (VAST), Hanoi, Vietnam. 
 
2.3. Extraction and Isolation  
  
The dried and powdered mixture of twigs and leaves 
of F. hodginsii (900 g) was extracted ultrasonically 
with methanol - water (90:10, v/v) at 40 
o
C, three 
times, each 4 h. After concentration under reduced 
pressure, the crude extract was suspended in water 
and sequentially partitioned in n-hexane, ethyl 
acetate and n-butanol. The organic solvents were 
evaporated to yield the corresponding extracts (14.0, 
  
VJC, 55(5), 2017  Trinh Thi Thuy et al.  
558 
18.3 and 13.2 g, respectively). The hexane extract 
(14.0 g) was subjected to silica gel column 
chromatography with gradient elution of n-hexane - 
EtOAc mixtures (from 100:1 to 70:30) to give 
twenty fractions (F1-F20). Fraction F10 was 
separated by a Sephadex LH-20 column with MeOH 
as eluent to give totarolone (1, 20 mg). Fraction F16 
was further purified on a silica gel column eluted 
with hexane-EtOAc (95:5) to yield 3β-hydroxy-
totarol (2, 10 mg). Fractions F16 and F12 were 
repurified on a Sephadex LH-20 column using 
methanol as eluent to give 13-oxo-15,16-dinorlabda-
8(17),11E-diene-19-oic acid (3, 10 mg) and 15-nor-
labda-8(17),12E-diene-14-carboxaldehyde-19-oic 
acid (4, 10 mg), respectively.  
Totarolone (3-oxototarol, 1): 
1
H-NMR (500 
MHz, CD3OD) δH: 6.95 (1H, d, J = 8.5 Hz, H-11), 
6.58 (1H, d, J = 8.5 Hz, H-12), 3.27 (1H, br s, H-15), 
3.02 (1H, dd, J = 17.0, 5.5  Hz, H-7a), 2.72 (1H, m, 
H-7b), 2.68 (1H, m, H-2a), 2.58 (1H, m, H-2b), 1.34, 
1.33 (each 3H, d, J = 6.5 Hz, H-15&H-16), 1.29 (3H, 
s, H-20), 1.17 (3H, s, H-19), 1.14 (3H, s, H-18); 
13
C-
NMR (500 MHz, CD3OD) δC: 220.56 (C-3), 155.12 
(C-13), 140.11 (C-9), 134.93 (C-8), 132.05 (C-14), 
124.81 (C-11), 115.58 (C-12), 51.52 (C-5), 48.32 (C-
4), 39.62 (C-1), 38.39 (C-10), 35.79 (C-2), 30.14 (C-
7), 28.85 (C-15), 27.30 (C-18), 25.07 (C-20), 21.68 
(C-6), 21.47 (C-19), 20.58, 20.51 (C-16 & C-17). 
3β-Hydroxytotarol (2): ESI-MS m/z: 285.1 [M-
H2O+H]
+
. 
1
H-NMR (500 MHz, CD3OD) δH: 6.92 
(1H, d, J = 8.5 Hz, H-11), 6.53 (1H, d, J = 8.5 Hz, H-
12), 3.24 (1H, dd, J = 11.5, 5.0  Hz, H-3),  2.96 (1H, 
dd, J = 16.5, 6.0  Hz, H-7a), 2.71 (1H, m, H-7b), 
1.33, 1.32 (each 3H, d, J = 6.5 Hz, H-15 & H-16), 
1.17 (3H, s, H-20), 1.07 (3H, s, H-19), 0.89 (3H, s, 
H-18); 
13
C-NMR (125 MHz, CD3OD) δC: 155.32 (C-
13), 142.29 (C-9), 134.89 (C-8), 132.07 (C-14), 
123.78 (C-11), 115.26 (C-12), 79.58 (C-3), 50.93 (C-
5), 39.87 (C-4), 39.27 (C-1), 38.56 (C-10), 30.29 (C-
7), 28.96 (C-2), 28.76 (C-19), 25.61 (C-20), 20.56 
(C-16&C-17), 20.43 (C-6), 16.08 (C-18). 
13-Oxo-15,16-dinor-labda-8(17),11E-diene-19-
oic acid (3): 
1
H-NMR (500 MHz, CD3OD) δH: 6.98 
(1H, dd, J = 16.0, 10.5, H-11), 6.12 (1H, d, J = 16.0, 
H-12), 4.83 (1H, d, J = 1.5, H-17a), 4.45 (1H, d, J = 
1.5, H-17b), 2.30 (3H, s, H-14), 1.24 (3H, s, H-18), 
0.87 (3H, s, H-20); 
13
C-NMR (125 MHz, CD3OD) 
δC: 200.88 (C-13), 180.12 (C-19), 149.89 (C-8), 
148.67 (C-11), 134.58 (C-12), 108.87 (C-17), 61.35 
(C-9), 56.38 (C-5), 45.08 (C-4), 42.13 (C-1), 40.95 
(C-10), 39.31 (C-3), 38.24 (C-7), 29.42 (C-18), 27.11 
(C-14), 26.33 (C-6), 20.86 (C-2), 14.14 (C-20). 
15-Nor-labda-8(17),12E-diene-14-
carboxaldehyde-19-oic acid (4): ESI-MS m/z: 303.1 
[M-H]
-
; 
1
H-NMR (500 MHz, CD3OD) δH: 9.31 (1H, 
s, H-14), 6.57 (1H, td, J = 6.0, 1.5 Hz, H-12), 4.87 
(1H, s, H-17a), 4.44 (1H, s, H-17b), 1.77 (3H, br s, 
H-16), 1.24 (3H, s, H-18), 0.74 (3H, s, H-20). 
13
C-
NMR (500 MHz, CD3OD) δC: 197.07 (C-14), 181.13 
(C-19), 158.69 (C-12), 149.57 (C-8), 140.01 (C-13), 
108.03 (C-17), 57.25, 57.15 (C-5 & C-9), 45.15 (C-
4), 41.38 (C-10), 40.55 (C-1), 39.42, 39.26 (C-3 & 
C-7), 29.54 (C-18), 27.24 (C-6), 25.73 (C-11), 21.14 
(C-2), 13.37 (C-20), 9.29 (C-16). 
 
3. RESULTS AND DISCUSSION 
 
The 
1
H NMR spectrum of 1 revealed two aromatic 
ortho-coupled protons at δH 6.95 (1H, d, J = 8.5 Hz, 
H-11), 6.58 (1H, d, J = 8.5 Hz, H-12), three singlet 
methyl groups at δH 1.29 (3H, s, H-20), 1.17 (3H, s, 
H-19), 1.14 (3H, s, H-18), an isopropyl group 
attached to a benzene ring by two doublet methyl 
signals at δH 1.34, 1.33 (each 3H, J = 6.5 Hz) and 
one methine proton at δH 3.27 (1H, br s, H-15), and 
aliphatic protons in the range from δH 1.73 to 3.03 
ppm. Its 
13
C-NMR and DEPT spectra showed signals 
of 20 carbon atoms including a ketone group, 5xCH3, 
4xCH2, 4xCH, and 6xCq. The presence of an 
aromatic ring was confirmed by two methine signals 
at δC 124.81 (C-11), 115.58 (C-12); one quaternary 
carbon bonded to an oxygen atom at δC 155.12 (C-
13) and three other quaternary carbons at δC 140.11 
(C-9), 134.93 (C-8), 132.05 (C-14). The HMBC 
correlations observed between H-16, H-17 and C-14; 
H-11 and the C-13 indicated that the isopropyl group 
was at C-14, and the phenolic hydroxyl group at C-
13. Thus, the structure of 1 was concluded to be 13-
hydroxy-8,11,13-totaratrien-3-one (3-oxototarol, 3-
ketototarol). This compound showed the strong 
activity against some gram-positive and gram-
negative bacteria as well as against some human 
pathogenic fungi [4]. 
The positive ESI-MS of 2 gave a molecular ion 
peak at m/z 285.1 [M+H-H2O]
+
. The spectral data 
and the molecular formula suggested that 2 had the 
same carbon skeleton as 1. The NMR spectra of 
compounds 2 were similar with those of 1 except 
some changes at C-3. The replacement of ketone 
group by a hydroxyl in the structure of 2 is indicated 
by the absence of the ketone group and the presence 
of a hydroxyl signal [δH 3.24 (dd, J = 11.5, 5.0 Hz, 
H-3)/δC79.58 (C-3)], in its NMR spectra. Thus, 
compound 2 was elucidated as 3β-hydroxytotarol 
(totaradiol) by comparison with data in the literature 
[5]. 
The molecular formula of 3 was determined to be 
C18H26O3 based on ion molecular peak at m/z 289.1 
[M-H]
-
 in the negative ESI-MS spectrum. In the 
1
H- 
and 
13
C-NMR spectra, characteristic signals for one  
  
VJC, 55(5), 2017                                                               Diterpenoids from Fokienia hodginsii.  
559 
 
Figure 1: The structure of compounds 1-4
ketone group (δC 200.88), one carboxylic acid (δC 
180.12), a trans-disubstituted double bond [δH 6.98 
(1H, dd, J = 16.0, 10.5 Hz, H-11)/δC 148.67; δH 6.12 
(1H, d, J = 16.0 Hz, H-12)/δC 134.58], an exocyclic 
methylene group [δH 4.83 (s), 4.45 (s), δC 108.87 (t), 
149.89 (s)], three tertiary methyl groups, six 
methylene groups, two methine groups were found. 
These data suggested that compound 3 is a nor-
labdane diterpenoid. The long-range correlations in 
the HMBC spectrum between H-18 and C-4, C-19; 
H-17 and C-7, C-9; H-11, H-12, H-14 and C-13 
were suggestive of that a carboxylic acid, an 
exocyclic methylene and a keton group must be 
located at C-4, C-8 and C-13, respectively. The 
NOEs correlations between H-9 and the methyl 
protons H-18 and H-5 implied that these protons 
were α-oriented. Combined its 1H-, 13C-NMR and 
2DNMR spectral data, compound 3 was determined 
as 13-oxo-15,16-dinorlabda-8(17),11E-diene-19-oic 
acid  [6]. 
The molecular formula of 4 was determined to 
be C19H28O3 based on a molecular ion peak at m/z 
303.1 [M-H]
- 
in the negative ESI-MS and 
combination with NMR data. The spectral data and 
the molecular formula suggested that 4 had the same 
carbon skeleton as 3 with a difference of a moiety 
side-chain at C-9. The 
1
H- and 
13
C-NMR spectra of 
4 showed the characteristic signals for the presence 
of a 3-methyl-4-oxo-2E-butenyl side chain, which 
were observed at δH 9.31 (1H, s, H-14), 6.57 (1H, td, 
J = 6.0, 1.5 Hz, H-12), 1.77 (3H, br s, H-16); δC 
197.07 (d, C-14), 158.69 (d, C-12), 140.01 (s, C-13), 
9.29 (q, C-16). By comparison of its 
1
H- and 
13
C-
NMR spectral data with those of 15-nor-labda-
8(17),12E-diene-14-carboxaldehyde-19-oic acid 
methyl ester [7], compound 4 was determined as 15-
norlabda-8(17),12E-dien-14-carboxaldehyde-19-oic 
acid. Recently, this compound was also isolated  
from  the twigs and leaves of Fokienia hodginsii 
growing in China [2]. 
Except 4, the remaining compounds 1-3 were 
isolated from this plant for the first time.  
 
Acknowledgment. We would like to thank the 
National Foundation for Science & Technology 
Development (NAFOSTED) of Vietnam for financial 
support for this research (code: 104.01-2013.62). 
 
REFERENCES 
 
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(2012). 
2. Xing-De Wu, Juan He, Xing-Yao Li,Liao-Bin Dong, 
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6. T. Katoh, R. Tanaka, M. Takeo, K. Nishide, M. 
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Corresponding author: Trinh Thi Thuy 
Institute of Chemistry 
Vietnam Academy of Science and Technology 
No. 18, Hoang Quoc Viet, Cau Giay District, Hanoi 
E-mail: thuy@ich.vast.vn.  
 
 
 
  
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Diterpenoids from Fokienia hodginsii.

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Diterpenoids from Fokienia hodginsii.

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