全 文 ：Isolation，Structure Modification and Cytotoxicity of
Benzopyranylisoflavones from Cudrania cochinchinensis Fruits
Liu Zhiping1，Wei Wanxing2，Zhou Min2，Liu Sheng2，Gan Chunfang1
(1College of Chemistry and Life science，Guangxi Tearchers University，Nanning 530001;
2College of Chemsitry and Chemical Engineering，Guangxi University，Nanning 530004)
Abstract Four benzopyranylisoflavones including alpinumisoflavone (1)，4’-O-methylalpinmumisoflavone
(2) ，4’-O-methylderrone (3) ，and isoderrone (4)along with two triterpenoid compounds (13α，14β，17α，20Ｒ)-
lanosta-7，24-diene-3β-ol (5)and (13α，14β，17α，20Ｒ)-lanosta-7，24-diene-3β-O-actate (6)were isolated from the
fruits of Cudrania cochinchinensis． In addition，five new isoflavone derivatives (7 ～ 11)were also obtained by the
methods of selective methylation，ethylation and O-prenylation using natural isoderrone 4 as a starting material． All
isoflavones were tested for the cytotoxicity against SGC-7901 cell lines by MTT method． The result showed that
compounds 4 and 10 have moderate cytotoxicity against SGC-7901 cell lines．
Keywords Cudrania cochinchinensis，Benzopyranylisoflavones，Isoderrone，Cytotoxicity
刘志平 男，34 岁，副教授，主要从事天然产物的分离、改性及活性研究。E-mail:liuzhiping828@ 126． com
国家自然科学基金项目(81060261)、广西自然科学基金项目(2014GXNSFBA118033)和广西高等学校科学技术研究项目
(YB2014226)资助
2014-01-13 收稿，2014-03-28 接受
构棘果中苯并吡喃异黄酮的分离、结构修饰及细胞毒性研究
刘志平1 韦万兴2 周 敏2 刘 盛2 甘春芳1
(1 广西师范学院化学与生命科学学院 南宁 530001;2 广西大学化学化工学院 南宁 530004)
摘 要 采用硅胶、聚酰胺层析方法从构棘果中分离得到了 4 个苯并吡喃异黄酮 alpinumisoflavone (1)、
4’-O-methylalpinmumisoflavone (2)、4’-O-methylderrone (3)、isoderrone (4)和 2 个三萜化合物 (13α，14β，17α，
20Ｒ)-lanosta-7，24-diene-3β-ol (5)、(13α，14β，17α，20Ｒ)-lanosta-7，24-diene-3β-O-actate (6)。以异黄酮
isoderrone为原料进行了结构修饰得到 5 个新异黄酮衍生物。所有异黄酮均采用噻唑蓝蛋白染色(MTT)法对
胃癌细胞 SGC-7901 的毒性进行了活性筛选，其中化合物 4 和 10 对人胃癌 SGC-7901 肿瘤细胞有中等程度的
抑制作用。
关键词 构棘 苯并吡喃异黄酮 异黄酮 Isoderrone 细胞活性
Cudrania cochinchinensis (C． cochinchinensis)
is distributed throughout the southern part of China，
Korea and Japan． The root of C． cochinchinensis has
been used for the treatment of humid jaundice，
gastric carcinoma， scabies， bruising and
dysmenorrhea，etc［1］． Isoprenylated xanthones［2，3］，
benzophenone［3］ and flavonoids［4］ isolated from the
roots of this plant were found to have antifungal［4］，
anti-microbial［5］， and cytotoxic［6］ activities．
However， the phytochemical constituents of C．
cochinchinensis fruits have not yet been investigated．
In order to separate some new bioactive constituents
from C． cochinchinensis， column chromatography
separation and purification of the 95% ethanol
(EtOH) extract were carried out to give four
benzopyranyl isoflavones (1 ～ 4)(Scheme 1)and
two triterpenoid compounds (5 ～ 6)． We also tried
to modify the chemical structure of the major
constituent and evaluate the biological activities of
the derivatives hoping to discover active compounds
with novel structures． As isoderrone 4 was the major
component isolated from the fruits of C．
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cochinchinensis，five new isoflavone derivatives 7-O-
methylisoderrone (7)，7-O-ethylisoderrone (8) ，5，
7-O-diethylisoderrone (9) ，7-O-prenylisoderrone
(10) and 5，7-O-diprenylisoderrone (11) were
synthesized using isoderrone 4 as a starting material．
1 Experimental
1. 1 Instruments and materials
The melting points were determined on an X4
micro apparatus． The 1H and 13C NMＲ spectra were
recorded on a Bruker avance-Ⅲ (300MHz)
spectrometer with TMS as the internal standard． HＲ-
ESI-MS was recorded on a Waters Xevo G2 QT of
MS Instrument． Silica gel (300 ～ 400 meshes)and
polyamide (60 ～ 100 meshes)were used for column
chromatography (CC)．
1. 2 Extraction and isolation
The fruits of C． cochinchinensis (2kg)were
soaked with 5L of EtOH three times for 3d． 12. 4g
precipitate extract were obtained after removal of
EtOH under reduced pressure． The precipitate
residue was subjected to silica gel column and eluted
with a petroleum ether (pet)-acetone gradient to
yield ten fractions (Fr． 1 ～ 10)． Further column
chromatography on silica gel of Fr． 2 eluted with pet-
acetone (20 ∶ 1，V ∶ V)affords 5 (110mg)and 6
(88mg)． Fr． 4 was passed over a silica gel column
by eluting with pet-acetone (8∶ 1，V ∶ V)to yield 2
(260mg)and 3 (75mg)． Whereas Fr． 7 was eluted
with pet-acetone (4 ∶ 1，V ∶ V)，and the crude
product was recrystallized in acetone-EtOH to give 4
(518mg)． Another mixture containing 4 from Fr． 7
(1. 67g)was further separated by polyamide column
chromatography eluted with CDCl3-MeOH (15 ∶ 1，
V∶ V)to afford 1 (23mg)．
1. 3 Preparation of isoderrone derivatives
Isoderrone (100mg， 0. 3mmol )， K2CO3
(50mg，0. 36mmol)and 15mL acetone were stirred
at 60℃ for 10min． To this solution was added
(CH3O)2SO2 (0. 35mL， 0. 36mmol) in 5 mL
acetone in one portion． The resulted mixture was
stirred at reflux for 2h，then K2CO3 was filtered off
and the filtrate was evaporated to dryness． The crude
solid was chromatographed on silica gel using pet /
ethyl acetone (7∶ 1，V∶ V)as the eluent to afford 7
as a white solid． Compounds 8 and 10 were prepared
by the similar method with 1. 2 equiv． of
(C2H5O)2SO2 and prenyl bromide respectively．
Compound 9 and 11 were prepared with the excess of
(C2H5O)2SO2 and prenyl bromide in the same way．
1. 4 Method for cytotoxicity study
The cytotoxic activities of compounds 1 ～ 4 and
7 ～ 11 were determined in vitro against SGC-7901
(human gastric carcinoma) tumor cell lines． The
MTT (3-(4， 5-Dimethylthiazol-2-yl )-2， 5-
diphenyltetrazolium bromide)［7］ method was used to
assay the anti-proliferative activity．
2 Ｒesults and Discussion
2. 1 Chemical constituents
Four benzopyranylisoflavones including
alpinumisoflavone［8］ (1)， 4’-O-methylalpinmum
isoflavone［8］(2)，4’-O-methylderrone (3)［9］，and
isoderrone (4)［10］ along with two triterpenoid
compounds (13α，14β，17α，20Ｒ)-lanosta-7，24-
diene-3β-ol (5)［11］，(13α，14β，17α，20Ｒ)-lanosta-
7，24-diene-3β-O-actate (6)［12］ were isolated from
the fruits of C． cochinchinensis． Compounds 3 and 4
were obtained from this genus for the first time．
Benzopyranylisoflavones were the main components
in the fruits of C． cochinchinensis．
Scheme 1 Structures of benzopyranylisoflavones 1 ～ 4
图式 1 苯并吡喃异黄酮化合物 1 ～ 4 的结构
2. 2 Isoderrone derivatives
Due to the fact that methyoxy，ethyoxy and
prenyoxy groups are substitutuents commonly found
in the structures of natural flavones，we designed
and synthesized five new isoderrone derivatives 7 ～
11 by the methods of alkylation or prenylation of 4．
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Ｒeagents and conditions，7:(CH3 )2 SO4，K2CO3 /Acetone，
reflux;8 and 9:(C2H5)2 SO4，K2CO3 /Acetone，reflux;10 and
11:Isoamylene bromide，K2CO3 /Acetone，reflux．
Scheme 2 Modificated routes to isoderron derivatives 7 ～ 11
图式 2 化合物 7 ～ 11 的结构及合成路线
7-O-methylisoderrone (7):white solid，yield
72. 1%，m． p． 165 ～ 167℃ ． 1H NMＲ (300MHz，
CDCl3)δ:12. 87 (s，1H，OH-5)，7. 86 (s，1H，
H-2) ，7. 24 (dd，J = 8. 1Hz，2. 1Hz，1H，H-6’) ，
7. 18 (d，J = 2. 1Hz，1H，H-2’) ，6. 85 (d，J =
8. 4Hz，1H，H-5’) ，6. 40 (d，J = 2. 4Hz，1H，H-
8) ，6. 39 (d，J = 2. 4Hz，1H，H-6) ，6. 36 (d，
J = 9. 9Hz，1H，H-4″) ，5. 66 (d，J = 9. 9Hz，1H，
H-3″) ，3. 87 (s，3H，OCH3)，1. 47 (s，6H，5″，
6″-CH3)．
13C NMＲ (75MHz，CDCl3)δ:180. 8，
165. 5，162. 7，157. 9，153. 3，152. 7，131. 1，
129. 5，126. 9，123. 6，122. 9，122. 1，121. 3，
116. 5，106. 2，98. 2，92. 4，76. 6，55. 8，64. 2，
28. 1． HＲ-ESI-MS ［M + H］+:351. 1227 (calcd
for C21H19O5:351. 1233)．
7-O-ethylisoderrone (8) :White solid，yield
77. 5%，m． p． 157 ～ 159 ℃ ． 1 H NMＲ (300MHz，
CDCl3)δ:12. 86 (s，1H，OH-5)，7. 82 (s，1H，
H-2) ，7. 23 (dd，J = 8. 1Hz，2. 1Hz，1H，H-6’) ，
7. 17 (d，J = 2. 1Hz，1H，H-2’) ，6. 84 (d，J =
8. 4Hz，1H，H-5’) ，6. 35 (d，J = 2. 4Hz，1H，H-
8) ，6. 35 (d，J = 2. 4Hz，1H，H-6) ，6. 35 (s，
1H，H-4″) ，5. 65 (d，J = 9. 9Hz，1H，H-3″) ，
4. 07 (q，J = 6. 6Hz，2H，OCH2)，1. 46 (s，6H，
5″，6″-CH3)，1. 44 (t，J = 6. 6Hz，3H，OCH3)．
13C NMＲ (75MHz，CDCl3) δ:180. 7，164. 9，
162. 6，157. 9，153. 3，152. 7，131. 1，129. 5，
126. 9，123. 5，123. 0，122. 1，121. 3，116. 5，
106. 1，98. 6，92. 8，76. 6，64. 2，28. 1，14. 6．
HＲ-ESI-MS［M + H］+:365. 1418 (calcd for C22
H21O5:365. 1389)．
7-O-diethylisoderrone (9):White solid，yield
81. 3%，m． p． 143 ～ 145 ℃ ． 1 H NMＲ (300MHz，
CDCl3)δ:12. 87 (s，1H，OH-5)，7. 86 (s，1H，
H-2) ，7. 25 (dd，J = 8. 4Hz，2. 7Hz，1H，H-6’) ，
7. 19 (d，J = 2. 1Hz，1H，H-2’) ，6. 85 (d，J =
8. 1Hz，1H，H-5’) ，6. 41 (d，J = 2. 4Hz，1H，H-
6) ，6. 39 (d，J = 2. 4Hz，1H，H-8) ，6. 37 (d，
J = 9. 9Hz，1H，H-4″) ，5. 66 (d，J = 9. 9Hz，1H，
H-3″) ，5. 47 ～ 5. 20 (m，1H，= CH) ，4. 58 (d，
J = 6. 6Hz，2H，OCH2)，1. 83 (s，3H，CH3)，
1. 78 (s，3H，CH3)，1. 47 (s，6H，5″，6″-CH3)．
13C NMＲ (75MHz，CDCl3) δ:180. 8，164. 8，
162. 6，157. 9，153. 3，152. 6，139. 3，131. 1，
129. 5，126. 9，123. 6 ，123. 0，122. 1，121. 3，
118. 6，116. 5，106. 1，98. 6，93. 1，76. 6，65. 4，
28. 1，25. 9， 18. 3． HＲ-ESI-MS ［M + H］+:
405. 1734 (calcd for C25H25O5:405. 1702)．
7-O-prenylisoderrone (10):White solid，yield
73. 7%，m． p． 118 ～ 120℃ ． 1 H NMＲ (300MHz，
CDCl3)δ:7. 73 (s，1H，H-2)，7. 22 (dd，J =
8. 1，2. 1Hz，1H，H-6’) ，7. 20 (d，J = 2. 1Hz，
1H，H-2’) ，6. 80 (d，J = 8. 1Hz，1H，H-5’) ，
6. 41 (d，J = 1. 8Hz，1H，H-8) ，6. 40 (d，=
1. 8Hz，1H，H-6) ，6. 34 (d，J = 9. 6Hz，1H，H-
4″) ，5. 61 (d，J = 9. 6Hz，1H，H-3″) ，4. 06 ～
4. 13 (m，4H，2CH2O)，1. 44 ～ 1. 56 (m，6H，
2CH3)，1. 44 (s，6H，H-5”，6”)．
13C NMＲ
(75MHz，CDCl3)δ:175. 4，163. 1 160. 8，159. 9，
152. 9，150. 0，130. 7，129. 8，127. 5，126. 0，
124. 5， 122. 4， 121. 0， 116. 1， 109. 9， 97. 3，
92. 9，76. 4，65. 0，64. 1，64. 2，28. 1，14. 6，
14. 6 (OCH3)． HＲ-ESI-MS［M + H］
+:393. 1718
(calcd for C24H25O5:393. 1702)．
5，7-O-diprenylisoderrone (11):White solid，
yield 84. 8%， m． p． 105 ～ 107℃ ． 1H NMＲ
(300MHz，CDCl3)δ:7. 74 (s，1H，H-2)，7. 20
～ 7. 28 (m，2H，H- 2’，6’) ，6. 80 (d，J =
8. 1Hz，1H，H-5’) ，6. 44 (d，J = 2. 1Hz，1H，H-
6) ，6. 40 (d，J = 2. 1Hz，1H，H-8) ，6. 35 (d，
J = 9. 9Hz，1H，H-4”) ，5. 62 (d，J = 9. 9Hz，1H，
H-3”) ，5. 50 ～ 5. 60 (m，2H，= CH) ，4. 64 (d，
J = 6. 9Hz，2H，OCH2)，4. 59 (d，J = 6. 9Hz，
2H，OCH2)，1. 73 ～ 1. 84 (m，12H，4CH3)，
1. 45 (s，6H，5″，6″-CH3)．
13C NMＲ (75MHz，
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CDCl3)δ:175. 3，162. 9，160. 7，157. 9，152. 9，
149. 9 139. 4， 137. 3， 130. 6， 129. 7， 127. 5，
126. 0，124. 5，122. 4，121. 0，119. 5，118. 6，
116. 1，110. 1，97. 8，93. 2，76. 4，66. 4，65. 3，
28. 1，25. 9，25. 8，18. 4，18. 3． HＲ-ESI-MS ［M
+ H］+: 473. 2349 (calcd for C30 H33 O5:
473. 2328)．
2. 3 Cytotoxicity
All isoflavones were determined in vitro against
SGC-7901 (human gastric carcinoma cell line)
tumor cell lines by MTT method (Tab． 1)．
Tab． 1 In vitro antitumor activities of isoflavones
表 1 异黄酮化合物的体外抗肿瘤活性
SGC-7901
IC50 /(μmol /L)
SGC-7901
IC50 /(μmol /L)
1 ＞ 120 7 ＞ 120
2 ＞ 120 8 ＞ 120
3 ＞ 120 9 ＞ 120
4 50. 3 10 62. 3
11 110. 6
Among them， isoderrone 4 was the most
effective compound against SGC-7901，with the IC50
value of 50. 3μmol /L． The cytotoxicity of 2，3，5，
7 ～ 9 and 11 were generally lower compared to 4，
suggesting -OH moiety at C-7 might be essential for
achieving high activity． Moreover，compounds 7 and
8 showed weaker activities compared with 10，
indicating that -OH moiety at C-7 substituted by
prenyl has better activities than substituted by
methyl or ethyl．
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