全 文 ： 90 Chin J Nat Med Mar. 2011 Vol. 9 No. 2
Chinese Journal of Natural Medicines 2011, 9(2): 0090−0093
doi: 10.3724/SP.J.1009.2011.00090
Chinese
Journal of
Natural
Medicines







A New Diphenylmethane Derivative from Uvaria kurizz
with Cardiovascular Activity
LU Zi-Ming, ZHANG Qing-Jian, CHEN Ruo-Yun, YU De-Quan*
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education; Institute of Ma-
teria Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050 China
Available online Mar. 2011
[ABSTRACT] AIM: To study the chemical constituents of Uvaria kurzii (King) P. T. (Annonaceae). METHOD: The chemical con-
stituents were isolated with silica gel and Sephadex LH-20 column chromatography and their structures were elucidated by spectro-
scopic and synthetic methods. RESULTS: A diphenylmethane derivative (1) together with 5 known ent-kaurane diterpenoids (2-6)
were isolated and identified as bis (4-octanoylphenyl) methane (1), ent-kaur-16-en-19-oic acid (2), grandifloric acid (3),
ent-kaur-15-en-17-ol-19-oic acid (4), ent-16α, 17-dihydroxykauran-19-oic acid (5) and ent-16β, 17-dihydroxykauran-19-oic acid (6).
CONCLUSION: Compound 1 was a new diphenylmethane derivative, and compounds 2-6 were isolated from the genus Uvaria for
the first time. Bioactivity test on isolated rat heart failure model suggested 1 could increase coronary blood flow and myocardial con-
tractive power compared with positive control ouabain.
[KEY WORDS] Annonaceae; Bis (4-octanoylphenyl)-methane; Cardiovascular-activity; Ent-kaurane diterpenoids; Uvaria kurzii
[CLC Number] R284.1 [Document code] A [Article ID] 1672-3651(2011)02-0090-04

1 Introduction
The genus Uvaria (Annonaceae) comprises about 150
species, which are distributed in tropical and semitropical
zones. Uvaria kurzii (King) P. T. is one of the 10 species
belonging to this genus found in China [1]. The motivation of
searching for bio-active compounds from rich Chinese plant
resources and making full use of them prompted us to inves-
tigate the constituents of this plant. Previous investigation on
the branches and leaves has led to the isolation of steroids
and flavonoids [2]. In this paper, one new compound, bis (4-
octanoylphenyl) methane (1), together with 5 known ent-
kaurane diterpenoids were isolated from this plant for the
first time. The biological assays indicated 1 could increase
coronary blood flow (CBF) and myocardial contractive
power.
2 Experimental
2.1 General experimental procedures
Melting points were detected on an XT4 100x micro-
melting point apparatus and are uncorrected. Optical rotations

The branches and leaves of Uvaria kurzii (King) P. T.
were collected from Jinghong county, Yunnan province,
China and identified by Prof. Jiang Kai-Jiao (Yunnan Branch
of Institute of Medicinal Plant Development, Chinese Acad-
emy of Medical Sciences and Peking Union Medical College,
China). A voucher specimen is deposited in Herbarium of
Yunnan Branch of Institute of Medicinal Plant Development,
Chinese Academy of Medical Sciences and Peking Union
Medical College, China (ID 3763).
[Received on] 13-Oct.-2010
[*Corresponding author] YU De-Quan: Prof., Tel: 86-10-63165224,
E-mail: dqyu@imm.ac.cn.
These authors have no any conflict of interest to declare.
were obtained on a PE Model 343 polarimeter. IR spectra
were recorded on a Nicolet Impact 400 spectrophotometer as
KBr disks. UV spectra were measured on Hitachi UV-240
and Shimadzu UV-241 spectrophotometers. Mass spectra
were obtained on VGZAB-2F (EI-MS), LC/MSD Trap-SL
(ESI-MS) instruments. NMR spectra were carried out on a
Varian Inova-500 spectrometer. Column chromatography:
silica gel (200-300 mesh, Qingdao Marine Chemical, Qing-
dao, China), Sephadex LH-20 (Amersham Pharmacia Bio-
tech), TLC: silica gel (GF254, Qingdao Marine Chemical,
Qingdao, China).
2.2 Plant material
2.3 Extraction and isolation
The dried and powdered plant material (10 kg) was ex-
tracted with 95% EtOH for three times under reflux. The
residue (1 670 g) was suspended in water and partitioned with
2011 年 3 月 第 9 卷 第 2 期

LU Zi-Ming, et al. /Chinese Journal of Natural Medicines 2011, 9(2): 90−93
CHCl3. The CHCl3 residue (310 g) was partitioned with pe-
troleum ether-90% CH3OH. The 90% CH3OH extract (220 g)
was subjected on silica gel column chromatography (1 500 g)
and eluted with a mixture of CHCl3-CH3OH with gradually
increasing polarity to afford 7 combined fractions (Frs. 1-7)
on the basis of TLC analysis. The pure compounds were
obtained either by direct crystallization or through further
purifications on column chromatography. Purification of Fr. 2
(7 g) by silica gel [petroleum ether-EtOAc (10 : 1)] and
Sephadex LH-20 [CHCl3-petroleum ether-CH3OH (5 : 5 : 1)]
column chromatography yielded compounds 1 (20 mg) and 7
(17 mg). Fr. 3 (9.5 g) was subjected on silica gel [petroleum
ether-EtOAc (10 : 1-1 : 1)] and Sephadex-LH 20 [CHCl3-
petroleum ether-CH3OH (5 : 5 : 1)] column chromatography
and afforded compounds 2 (21 mg), 3 (15 mg), 4 (16 mg), 5
(64 mg), 6 (35 mg).
3 Structural identification
Compound 1 was obtained as colorless needle from
petro-CHCl3. HREI-MS showed an ion peak at m/z 420.301 3
[M]+, which was consistent with the molecular formula
C29H40O2. The UV spectrum exhibited absorption maximum
at λmax (nm) 256, similar to that of benzene moiety. The IR
spectrum (KBr) displayed absorption bands for methyl and
methylene (2 958, 2 925, 2 875 and 2 848 cm−1), conjugated
carbonyl (1 628 cm−1) group and aromatic moiety (1 603 and
1 570 cm−1). Fifteen carbon and twenty proton signals were
observed in the 13C and 1H NMR spectra of 1, respectively.
Combining with the HREI-MS result, it could be concluded
that 1 possessed a symmetrical structure skeleton The
AA′BB′ system at δ 7.79 (4H, d, J = 8.1 Hz) and 7.26 (4H, d,
J = 8.1 Hz) in 1H NMR spectrum and the carbon signals at δ
145.4 (2C), 135.4 (2C), 129.1 (4C), 128.5 (4C) revealed the
presence of p-substituted benzene system. The presence of
the octanoyl groups was evidenced by the proton signals at δ
2.92 (4H, t, J = 6.9 Hz), 1.71 (4H, pent, J = 6.9 Hz), 1.28-
1.38 (16H, m), and 0.87 (6H, t, J = 7.2 Hz) in the 1H NMR
spectrum and the carbon signals at δ 200.2 (2C), 38.6 (2C),
31.7 (2C), 29.3 (2C), 29.1 (2C), 24.4 (2C), 22.6 (2C), 14.1
(2C) in the 13C NMR spectrum. The protons and carbon cor-
responding to the signals at δ 4.07 (2H, s) and 41.8 (1C) re-
spectively were assigned to the methene group, which was
the symmetrical center of the molecule structure. The assign-
ment was confirmed by the DEPT experiment revealing in-
formation as: δ 200.2 (C=O), 145.4 (=C=), 135.4 (=C=),
129.1 (CH), 128.5 (CH), 41.8 (CH2), 38.6 (CH2), 31.7 (CH2),
29.3 (CH2), 29.1 (CH2), 24.4 (CH2), 22.6 (CH2), 14.1 (CH3).
Combining all the information obtained from EI-MS, HREI-
MS, 1H NMR, 13C NMR and DEPT analyses, the structure of
1 was elucidated as bis(4-octanoyl-phenyl) methane. Com-
pound 1 was synthesized. The melting points of the synthe-
sized and the isolated were same. Their Rf values of TLC and
the data of 1H NMR and IR were identical. To the best of our
knowledge, compound 1 was a new compound (Fig. 1).

Fig. 1 Structures of compounds 1-6
Bis (4-octanoylphenyl) methane (1) Colorless needles
(petroleum ether-CHCl3), mp 81-82 °C. HREI-MS m/z
420.301 3 [M]+, (Calcd. for C29H40O2 420.302 8). UV λmax
(tetrahydrofuran) (nm): 256. IR (KBr, cm−1): 2 958, 2 925,
2 875, 2 848, 1 628, 1 603, 1 570. 1H NMR (500 MHz,
CDCl3) δ: 7.79 (4H, d, J = 8.1 Hz), 7.26 (4H, d, J = 8.1 Hz),
4.07 (2H, s), 2.92 (4H, t, J = 6.9 Hz), 1.71 (4H, pent, J = 6.9
Hz), 1.28-1.38 (16H, m), 0.87 (6H, t, J = 7.2 Hz); 13C NMR
(125 MHz, CDCl3) δ: 200.2 (C=O), 145.4 (=C=), 135.4
(=C=), 129.1 (CH), 128.5 (CH), 41.8 (CH2), 38.6 (CH2), 31.7
(CH2), 29.3 (CH2), 29.1 (CH2), 24.4 (CH2), 22.6 (CH2), 14.1
(CH3). EI-MS m/z [M]+ 420 (3), 336 (30), 321 (100), 252
(73), 237 (20), 218 (25), 203 (21), 194 (14), 119 (4).
Synthesis of 1
(a) Preparation of n-octanoyl chloride N-octanoic
acid (7.2 g, 0.05 mol) was put into a round flask (250 mL).
Stirring magnetically under ice-water bath, SOCl2 (11.9 g, 0.1
mol) was added dropwise in 2 h. After being warmed up to
room temperature naturally while stirring, the reaction was
kept for one hour. The excess SOCl2 was removed under
reduced pressure, resulting light yellow sticky liquid as
n-octanoyl chloride.
(b) Preparation of 1 from n-octanoyl chloride and
diphenylmethane AlCl3 (6.7 g, 0.05 mol) was suspended
in dried CH2Cl2 (40 mL) in a round flask (100 mL). Stirring
magnetically below –20 °C, n-octanoyl chloride was added
dropwise in 2 h. AlCl3 was dissolved step by step and the
solution exhibited red. Then a solution of diphenylmethane
(0.84 g, 0.005 mol) in dried CH2Cl2 (40 mL) was added
dropwise in 6 h. After being warmed up to room tempera-
ture naturally while stirring, the reaction was set aside for 12
h. The solution turned from red to black. After that, the reac-
tion was stopped by slowly pouring the solution into
ice-water. After keeping stirring for one hour, the organic
layer and water layer separated. Then the water phase was
extracted with CH2Cl2 (50 mL × 2). The organic layers were
combined and washed by saturated Na2CO3 solution (twice),
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LU Zi-Ming, et al. /Chinese Journal of Natural Medicines 2011, 9(2): 90−93
92 Chin J Nat Med Mar. 2011 Vol. 9 No. 2
and then by distilled water (twice). After being dried with
anhydrous Na2SO4 overnight, a residue (2.3 g) was obtained
by removing the solvent of the filtrate under reduced pressure.
After recrystallizing from petroleum ether-CHCl3, white nee-
dles (1.5 g) were gained with a yield of 71%.
Ent-kaur-16-en-19-oic acid (2) White crystal (petro-
leum ether-CHCl3), mp 168-169 °C. [α]D25 −133.2° (c 0.3,
CHCl3). ESI-MS m/z 301 [M – H]+. 1H NMR (CDCl3) δ:
12.20 (1H, s, 19-COOH), 4.80 (1H, s, 17-Ha), 4.74 (1H, s,
17-Hb), 0.95 (3H, s, 20-CH3), 1.24 (3H, s, 18-CH3);
The effects of 1 on rat heart failure model were detected.
The experimental models of heart failure were established by
rat coronary artery ligature 13C NMR (C5D5N) δ: 40.7 (C-1), 19.1 (C-2), 37.7 (C-3), 43.7
(C-4), 57.0 (C-5), 21.8 (C-6), 41.2 (C-7), 44.2 (C-8), 55.0
(C-9), 39.7 (C-10), 18.4 (C-11), 33.1 (C-12), 43.8 (C-13),
39.6 (C-14), 48.9 (C-15), 155.8 (C-16), 103.0 (C-17), 28.9
(C-18), 185.1 (C-19), 15.6 (C-20). The above data are identi-
cal with those of ent-kaur-16-en-19-oic acid [3-4].
Grandifloric acid (3) White crystal (CHCl3-CH3OH),
mp 199-202 °C. [α] D 25 −88.5° (c 0.62, C5H5N). ESI-MS m/z
317 [M − H]+. 1H NMR (C5D5N) δ: 14.75 (1H, brs, 19-
COOH), 1.35 (3H, s, 18-CH3), 1.19 (3H, s, 20-CH3), 5.49
(1H, s, H-17a), 5.19 (1H, s, H-17b), 4.16 (1H, s, H-15);
13C NMR (C5D5N) δ: 41.2 (C-1), 19.9 (C-2), 38.8 (C-3), 44.0
(C-4), 57.2 (C-5), 22.1 (C-6), 40.0 (C-7), 48.4 (C-8), 54.0
(C-9), 39.8 (C-10), 18.8 (C-11), 33.1 (C-12), 42.9 (C-13),
36.7 (C-14), 82.7 (C-15), 161.4 (C-16), 107.7 (C-17), 29.4
(C-18), 180.3 (C-19), 16.3 (C-20). The above data are identi-
cal with those of ent-kaur-16-en-19-oic acid [5].
Ent-kaur-15-en-17-ol-19-oic acid (4) White powder
(CHCl3-CH3OH), mp 243-244 °C. [α]D 25−73.3° (c 0.58,
C5H5N). ESI-MS m/z 317 [M − H]+. 1H NMR (C5D5N) δ:
14.75 (1H, brs, 19-COOH), 1.35 (3H, s, 18-CH3), 1.19 (3H, s,
20-CH3), 5.62 (1H, s, 15-H), 4.48 (2H, s, 17-Ha/b); 13C NMR
(C5D5N) δ: 41.2 (C-1), 19.9 (C-2), 38.8 (C-3), 44.0 (C-4),
56.8 (C-5), 21.7 (C-6), 44.3 (C-7), 49.2 (C-8), 48.2 (C-9),
40.2 (C-10), 19.3 (C-11), 25.9 (C-12), 41.5 (C-13), 36.4
(C-14), 134.5 (C-15), 148.1 (C-16), 60.6 (C-17), 29.4 (C-18),
180.3 (C-19), 15.9 (C-20). The above data are identical with
those of ent-kaur-16-en-19-oic acid [6].
Ent-16α, 17-dihydroxykauran-19-oic acid (5) White
powder(CH3OH), mp 298-300 °C, [α]D25 −111.2° (c 0.3,
CHCl3). ESI-MS m/z 335 [M − H]+. 1H NMR (C5D5N) δ:
3.85 (1H, d, J = 15.0 Hz, 17-Ha), 3.77 (1H, d, J = 15.0 Hz,
17-Hb), 1.36 (3H, s, 18-CH3), 1.23 (3H, s, 18-CH3);
13C NMR (C5D5N) δ: 41.2 (C-1), 19.9 (C-2), 38.8 (C-3), 44.0
(C-4), 57.1 (C-5), 22.5 (C-6), 42.5 (C-7), 43.9 (C-8), 56.8
(C-9), 40.1 (C-10), 19.5 (C-11), 27.6 (C-12), 41.7 (C-13),
38.6 (C-14), 53.5 (C-15), 79.8 (C-16), 70.8 (C-17), 29.4
(C-18), 180.2 (C-19), 16.0 (C-20). The above data are identi-
cal with those of ent-kaur-16-en-19-oic acid [6-8].
ent-16β, 17-dihydroxykauran-19-oic acid (6) White
crystal (CHCl3-CH3OH), mp 266-267 °C, [α]D 25 –88.5° (c 0.6,
C5H5N). ESI-MS m/z 335 [M – H]+. 1H NMR(C5D5N) δ:
1.34 (3H, s, 18-CH3), 1.19 (3H, s, 20-CH3), 4.13 (1H, d, J =
11.0 Hz, H-17a), 4.05 (1H, d, J = 11.0 Hz, H-17b); 13C NMR
(C5D5N) δ: 41.0 (C-1), 19.8 (C-2), 38.7 (C-3), 43.9 (C-4),
57.0 (C-5), 23.0 (C-6), 42.8 (C-7), 45.0 (C-8), 56.3 (C-9),
40.0 (C-10), 19.0 (C-11), 26.8 (C-12), 45.9 (C-13), 37.8
(C-14), 53.9 (C-15), 81.6 (C-16), 66.5 (C-17), 29.3 (C-18),
180.1 (C-19), 16.0 (C-20). The above data are identical with
those of ent-kaur-16-en-19-oic acid [6, 8-9].
5 Bioactivity study of 1 on isolated rat heart
[10-11]. The effects of the com-
pounds on rat heart failure model were detected. (a) Ouabain
(6.5 mmol·L−1) was added into the perfusion system, and the
K-H solution was also added into till the concentration of
ouabain was 1 × 10−5 mol·L−1. Then the rat heart was per-
fused. The indexes were recorded for first 10 minutes as
positive controls. (b) Similarly as above, a solution of 1 in
DMSO was added into the perfusion system, and the K-H
solution was also added into till the concentration of 1 was 1
× 10−5 mol·L−1. Then the rat heart was perfused. And the
indexes were recorded for first 10 min. The bioactivities was
showed as CBF and dp·dtmax−1 which expressed myocardial
contractive power.
The results of activity test suggested that 1 increased
CBF and myocardial contractive power compared with posi-
tive control (Table 1). However the increasing of myocardial
contractive power was irregular and the increasing of the
intensity was stronger. The heart came to death after 10-20
minutes. The possible reasons might be as follows: (a) The
toxicity of 1 was higher because of its higher dose. (b) 1 was
water-insoluble. (c) 1 was metabolized quickly. The experi-
ments of dose-effect relationship about 1 on normal hearts
and heart failure models in vitro and vivo were on going.
Table 1 The activity-testing results of 1 and ouabain on rat
heart failure model
Sample c/ mol·L−1 CBF dp·dtmax−1
1 1 × 10−5 60% ↑a 27.38%-136.37% ↑a
Ouabain 1 × 10−5 0-30% ↑a 18.03%-31.70% ↑a
a ‘↑’ indicates the increase.
Acknowledgements
The authors are grateful to the staff of the Department of
Instrumental Analysis of Institute of Materia Medica, Chinese
Academy of Medical Sciences and Peking Union Medical
College for all spectra analysis. The authors also thank Mr.
Zhu Hai-Bo and Ms. Liu Hong-Yan of the Department of
Pharmacology of Institute of Materia Medica, Chinese Aca-
demy of Medical Sciences and Peking Union Medical Col-
lege for bioactivity tests.
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黄花紫玉盘中一个具心血管活性的新二苯甲烷类衍生物
吕子明, 张庆建, 陈若芸, 于德泉*
中国医学科学院 北京协和医学院 中草药物质基础和资源利用教育部重点实验室, 北京 100050
【摘 要】 目的：研究番荔枝科植物黄花紫玉盘(Uvaria kurzii)中的化学成分。 方法：采用硅胶和凝胶柱色谱方法进行分
离纯化, 利用谱学和合成方法鉴定化合物的结构。 结果：分离得到一个新的二苯甲烷类衍生物(1)和 5 个已知贝壳杉烷型化合物
(2-6), 分别鉴定为双(4-辛酰基苯基)甲烷 (1), 对映-16-贝壳杉烯-19-酸 (2), 大花酸 (3), 对映-15-贝壳杉烯-17-醇-19-酸 (4), 对
映-16α, 17-二羟基贝壳杉烷-19-酸 (5), 和对映-16β, 17-二羟基贝壳杉烷-19-酸(6)。 结论：化合物 1 是一个新的二苯甲烷类衍生
物, 化合物 2-6 皆为紫玉盘属植物中首次分到。离体大鼠心衰试验表明, 与对照药哇巴因比较, 化合物 1 能增加冠脉血流量和
增强心肌收缩力。
【关键词】 番荔枝科; 双(4-辛酰基苯基)-甲烷; 心血管活性; 对映-贝壳杉烷型二萜; 黄花紫玉盘


·Information·

10th National Conference on Medicinal
Plants and Phytomedicines
Theme: Sustainable Utilization of Medicinal Plant Resources
Start Date: 2011-8-10
End Date: 2011-8-12
Country: China
Venue name: Kunming
Organized by: Botanical Society of China (BSC) Kunming Institute of Botany, Chinese Academy of Sciences (KIB, CAS)
Contact person: Ms Li Li-Ling
Tel/Fax: 0871-5223262
Email: nhtan2011@mail.kib.ac.cn
Useful link: http://medplant2011.kib.ac.cn.
General Information:
The scientific program will mainly include the progress, survey, identification, active
constituents, conservation, sustainable utilization, R & D, GAP and industrialization of
the resources of medicinal plants and phytomedicines. This conference will be a sig-
nificant platform to gather scientists, specialists, and young researchers in the field of
medicinal plants and phytomedicines, and a good opportunity for communication and
collaboration.

2011 年 3 月 第 9 卷 第 2 期 Chin J Nat Med Mar. 2011 Vol. 9 No. 2 93