Journal of Asian Natural Products Research

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Two new diterpenoids from Croton crassifolius

Ying Hu , Lei Zhang , Xiao-Qiong Wen , Xiao-Jun Zeng , Wen Rui & Ying-Zhou
Cen

To cite this article: Ying Hu , Lei Zhang , Xiao-Qiong Wen , Xiao-Jun Zeng , Wen Rui & Ying-
Zhou Cen (2012) Two new diterpenoids from Croton�crassifolius , Journal of Asian Natural Products
Research, 14:8, 785-788, DOI: 10.1080/10286020.2012.694872

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Published online: 14 Jun 2012.

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Journal of Asian Natural Products Research
Vol. 14, No. 8, August 2012, 785–788

Two new diterpenoids from Croton crassifolius

Ying Hua, Lei Zhanga*, Xiao-Qiong Wena, Xiao-Jun Zenga, Wen Ruib and
Ying-Zhou Cena*
a
Department of Chemistry, Jinan University, Guangzhou 510632, China; bDepartment of Chemistry,
Guangdong Pharmaceutical University, Guangzhou 510006, China
(Received 14 January 2012; final version received 15 May 2012)

Two new clerodane-type diterpenoids were isolated from the roots of Croton crassifolius
Geisel. The structures of these compounds were elucidated as 9-[2-(2(5H)-furanone-4-
yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acid (1) and
methyl 9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydro-
naphthalene-4-carboxylic ester (2) by spectroscopic methods.
Keywords: Euphorbiaceae; Croton crassifolius; clerodane-type diterpenoid

1. Introduction structural elucidation of the two

Croton crassifolius (Euphorbiaceae) is compounds.
mainly distributed in the south region of
China. Its roots can be used for medicinal 2. Results and discussion
purposes, such as pain inhibition, dispelling Compound 1 was isolated as colorless
the swelling and inflammation [1]. People of needle crystal with mp 181– 1828C and
Yao minority usually use the rhizome as ½a
20
D þ 5.7 (c ¼ 0.10, CHCl3). The mol-
traditional herbal medicine to cure rheuma- ecular formula was established as
tism and injuries from falls and to alleviate C20H28O4 on the basis of its HR-ESI-MS
pain. Moreover, Boonyarathanakornit et al. at m/z 332.1984 [M]þ. The IR spectrum
[2] reported that C. crassifolius exhibited indicated the presence of hydroxyl (3340 –
anticancer activity. From the view of 3023 cm21), carbonyl (1733 cm21), and
phytochemistry, the genus Croton is a rich double bonds (1625 cm21). The 1H NMR
source of diterpenoids, mainly with a spectrum (Table 1) showed signals of three
clerodane skeleton. Studies have shown methyls at dH 0.89 (3H, d, J ¼ 6.8 Hz),
that clerodane-type diterpenoids demon- 0.93 (3H, s), 1.29 (3H, br s), one
strated various biological activities [3–5]. oxygenated methylene at dH 4.73 (2H, d,
Therefore, the search for new clerodane- J ¼ 1.7 Hz), and one olefinic methine at dH
type diterpenoids has kindled great interest 5.84 (1H, t, J ¼ 1.7 Hz). The 13C NMR
in chemist. C. crassifolius is frequently used spectrum showed 20 carbon signals,
as a herbal medicine, but the roots of including 3 methyl, 8 methylene, 2
C. crassifolius have not been investigated so methine, and 7 quaternary carbons. In its
13
widely. Our phytochemical investigation of C NMR spectrum, two carbonyls at dC
the roots of C. crassifolius has resulted in the 182.7 and 174.1, four olefinic carbons
isolation of two new clerodane-type diter- (dC 115.1, 132.6, 135.2, and 171.0), and
penoids. Here, we report the isolation and the carbons belonging to a,b-unsaturated

*Corresponding authors. Email: [email protected]; [email protected]

ISSN 1028-6020 print/ISSN 1477-2213 online

q 2012 Taylor & Francis
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786 Y. Hu et al.

Table 1. 1H and 13C NMR spectral data of compounds 1 and 2 (400 MHz for 1H and 100 MHz for
13
C, in CDCl3).
1 2
Position dH (J in Hz) dC dH (J in Hz) dC
1a 1.69, m 25.2 1.69, m 25.2
1b 2.13, m 2.12, m
2 1.66, m 20.0 1.63, m 20.1
3a 1.47, m 36.5 1.43,m 36.4
3b 2.08, m 2.02, m
4 – 47.5 – 47.7
5 – 132.6 – 133.0
6a 1.86, br d (16.9) 27.7 1.73, br d (16.9) 27.6
6b 2.07, m 2.04, m
7 1.49, m 26.8 1.47, m 26.8
8 1.59, m 33.8 1.55, m 33.8
9 – 41.1 – 41.1
10 – 135.2 – 134.6
11 1.66, m 33.4 1.67, m 33.5
12a 2.00, m 23.7 2.00, m 23.7
12b 2.31, dt (17.0, 7.9) 2.32, dt (16.7, 7.8)
13 – 171.0 – 171.1
14 5.84, t (1.7) 115.1 5.85, t (1.7) 115.1
15 – 174.1 – 174.1
16 4.73, d (1.7) 73.1 4.75, d (1.7) 73.1
17 0.89, d (6.8) 16.1 0.90, d (6.8) 16.1
18 – 182.7 – 177.9
19 1.29, br s 24.3 1.27, br s 24.5
20 0.93, s 20.7 0.94, s 20.7
21 3.65, br s 51.9
ZOCH3

g-lactone moiety (dC 171.0, 115.1, 174.1, pounds shared the same stereochemistry.
and 73.1) were observed. From the above Thus, the structure of compound 1 was
observations and by comparing with established as 9-[2-(2(5H)-furanone-4-
previously reported compounds from the yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-
title plant, compound 1 was suggested to octahydronaphthalene-4-carboxylic acid.
be clerodane-type diterpenoid [6 – 8]. Compound 2 was isolated as colorless
Comparison of 1H and 13C NMR spectral needle crystal with mp 100– 1018C and
data of 1 with those of 5-[2-(furan-4- ½a
20
D þ 8.0 (c ¼ 0.12, CHCl3). The mol-
yl)ethyl]-1,5,6-trimethyl-1,2,3,4,5,6,7,8- ecular formula was established as
octahydronaphthalene-carboxylic acid (3) C21H30O4 on the basis of its HR-ESI-MS
indicated their structural similarity [9]. at m/z 346.2135 [M]þ. The IR spectrum
The obvious difference was that the furan indicated the presence of carbonyls (1777
ring in compound 3 was substituted by the and 1751 cm 21) and double bonds
a,b-unsaturated g-lactone ring in com- (1638 cm21). The 13C NMR spectrum
pound 1. Meanwhile, the NOESY corre- showed 21 carbon signals, including 4
lations between H-19 and H-17 and methyl, 8 methylene, 2 methine, and 7
between H-17 and H-20 were observed in quaternary carbons. The 1H NMR spec-
compound 1, suggesting that both com- trum (Table 1) showed characteristic
 Journal of Asian Natural Products Research 787

O O
photometer with Centaurus FT-IR Micro-
15 16 scope (Welltech Enterprises, Capitol
13 Heights, Maryland, USA). 1H and 13C
14
NMR spectra (CDCl3) were recorded on a
12
20
Varian Inova-400 MHz spectrometer with
11 HMBC
trimethylsilyl as an internal standard
17
2 1 9 8 (Varian, Palo Alto, CA, USA). The EI-
10
MS and HR-ESI-MS were measured on
3 6
NOESY ABI 4000 Q-Trap and Acquity UPLC-Q
4 5 7
21 18 Micro mass spectrometers, respectively
ROOC (Advanced Bionics, Kanasa, MO, USA).
19
All the solvents used were of analytical
R=H 1
grade. Sephadex LH-20 (Pharmacia Bio-
R=CH3 2
tech, Svensk, Sweden) and silica gel
(200 –300 mesh, Qingdao Marine Chemi-
Figure 1. The key HMBC and NOESY
correlations of 1 and 2. cal Company, Qingdao, China) were used
for column chromatography (CC), and
precoated silica gel GF254 plates were used
for thin layer chromatography (Qingdao
signals of four methyls at dH 0.90 (3H, d, Marine Chemical Company).
J ¼ 6.8 Hz), 0.94 (3H, s), 1.27 (3H, br s),
3.65 (3H, s), one oxygenated methylene at 3.2 Plant materials
dH 4.75 (2H, d, J ¼ 1.7 Hz), and one
olefinic methine at dH 5.85 (1H, t, The dry roots of C. crassifolius were
J ¼ 1.7 Hz). The 1H and 13C NMR spectral collected from Chinese medicine market
data of 2 were similar to those of 1, except of Qingping, Guangzhou, China, in April
for the appearance of a methoxyl 2010 and authenticated by Prof. Yuewen
group. The HMBC correlation of OMe- Cai, Guangdong Food and Drug Voca-
18 (dH 3.65, s) with C-18 (dC 177.9) tional College, China. A voucher specimen
established the location of the methoxyl at (YH09600) is deposited in our laboratory,
C-18. The NOESY correlation between H- Department of Chemistry, Jinan Univer-
19 and H-17 and between H-17 and H-20 sity, China.
was observed. Therefore, the structure of 2
was established as methyl 9-[2-(2(5H)- 3.3 Extraction and isolation
furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2, The dry roots of C. crassifolius (7 kg)
3,4,5,6,7,8-octahydronaphthalene-4-car- were treated with 95% ethanol at room
boxylic ester (Figure 1). temperature for three times. After evap-
oration of ethanol in vacuum, the residue
(573 g) was suspended in water (1.5 liters)
3. Experimental
and then extracted successively with
3.1 General experimental procedures petroleum ether (3 £ 1.5 liters), EtOAc
Melting points were determined using an (3 £ 1.5 liters), and n-BuOH (3 £
X-6 micro melting point apparatus and are 1.5 liters). Removal of the solvent from
uncorrected (Taike Enterprises, Beijing, the extract under reduced pressure gave
China). Optical rotations were measured 164 g (petroleum ether), 289 g (EtOAc),
using a PerkinElmer model 341 polari- and 63 g (n-BuOH) of dark brown oily
meter (Welltech Enterprises, Capitol residues. The EtOAc extract (289 g) was
Heights, Maryland, USA). The IR spectra subjected to CC over silica gel (200 – 300
were recorded on a Nicolet 6700 spectro- mesh) and was eluted with petroleum
788 Y. Hu et al.

ether – EtOAc gradient system to yield HR-ESI-MS: m/z 346.2135 [M]þ (calcd
fractions 1 – 16. Fraction 5 (3 g) was for C21H30O4, 346.2139).
further purified by repeated silica gel CC
(300 – 400 mesh) with petroleum ether –
EtOAc (8:2, 7:3, and 3:7) to get fractions
A, B, and C. Recrystallization of Fr. A Acknowledgments
yielded compound 1 (20 mg). Fraction 6 This study was financially supported by the
National Natural Science Foundation of China
(5 g) was eluted with petroleum ether – (Nos 20772047 and 21310104) and Natural
EtOAc (7:3) over silica gel column and Science Foundation of Guangdong Province
crystallized in EtOAc to give compound 2 (No. 32210018).
(81 mg).

3.3.1 9-[2-(2(5H)-furanone-4-yl)ethyl]- References

4,8,9-trimethyl-1,2,3,4,5,6,7,8- [1] S.D. Deng, The List of Commonly Used
Herbs in Hainan (China Science and
octahydronaphthalene-4-carboxylic acid Technology Publishing, Beijing, 2006),
(1) p. 19.
Colorless needle crystal; mp 181 –1828C; [2] L. Boonyarathanakornit, C.T. Che, H.H.S.
Fong, and N.R. Farnsworth, Planta Med.
½a
20
D þ 5.7 (c ¼ 0.10, CHCl3); IR (KBr) 54, 61 (1988).
nmax (cm21): 3195, 2927, 1733, 1625, [3] M.L. Peres, M.G. Pizzolatti, R.A. Yunes,
1460, 1224, 1174, 1016, 897, 857; for 1H and F.D. Monache, Phytochemistry 49, 171
and 13C NMR spectral data (CDCl3), see (1998).
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I.A. Khan, M.D. Harries, and D.E. Wedge,
(calcd for C20H28O4, 332.1982).
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[5] C. Demetzos, K. Dimas, and S. Hatzianto-
3.3.2 Methyl 9-[2-(2(5H)-furanone-4- niou, Planta Med. 67, 614 (2001).
yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8- [6] F.M. Harraz, M.J. Pcolinski, and
octahydronaphthalene-4-carboxylic ester R.W. Doskotch, J. Nat. Prod. 59, 5 (1996).
[7] N. Hara, H. Asaki, Y. Fujimoto,
(2)
Y.K. Gupta, and A.K. Singh, Phytochem-
Colorless needle crystal; mp 100 –1018C; istry 38, 189 (1995).
½a
20
D þ 8.0 (c ¼ 0.12, CHCl3); IR (KBr)
[8] J. Jiang, Z.X. Zhi, and M. Ji, Chem. Ind.
nmax (cm21): 2941, 1777, 1751, 1724, Times 21, 49 (2007).
[9] M. Kanlayavattanakul, N. Ruangrungsi,
1638, 1466, 1430, 1237, 1161, 1102, 1026, T. Watanabe, M. Kawahata, B. Therrien,
975, 885, 859; for 1H and 13C NMR K. Yamaguchi, and T. Ishikawa, J. Nat.
spectral data (CDCl3), see Table 1. Prod. 68, 7 (2005).