全 文 ：中　国　药　科　大　学　学　报
Journal of China Pharmaceutical University　2003 ,34(2):125 ～ 127
Chromones from Angelica morri Hayata
SUN Shi1 , 2 ,XU Ling-Ling1 ,KONG Ling-Yi1 ,ZHANG Han-Qing2 ,HE Shan-An2
1
Department of Natural Medicinal Chemistry , China Pharmaceutical University , Nanjing 210038 , China;
2Key Lab for Plant Ex-Situ Conversition , Institute of Botany , Jiangsu Province &Chinese Academy of Sciences , Nanjing
210014 , China
【ABSTRACT】　AIM:Bioactive constituents were expected to be obtained from the roots of Angelica morri Hayata.
METHOD:They were extracted with 95% alcohol and isolated by using column chromatography and recrystallization methods.
The structures were elucidated by means of physico-chemical data and UV , IR, 1HNMR, 13CNMR, and EIMS.The inhibitory ef-
fect on the constriction of rat aortic rings was induced by K+or Ca2+.RESULT:3′S-(-)-hamaudol , 3′S-(-)-Ο-acetylhamau-
dol , 3′R-(+)-hamaudol , and (±)-hamaudol were isolated from the pieces of Radix Angelica Morri.The inhibitory rate of 3′
S-(-)-Ο-acetylhamaudol and(±)-hamaudol on the above pharmacologic model appears the relation of quantity response.
CONCLUSION:All the above compounds were found in this species for the first time , and(±)-hamaudol is a new.One of ef-
fect mechanisms of 3′S-(-)-Ο-acetylhamaudol and(±)-hamaudol diluted aorta could contribute to be inhibiting Ca2+ influx of
vascular smooth muscle.
【KEY WORDS】　Angelica morri Hayata;Chromone;Rat aorta;Umbelliferae
【CLC Number】　R284.1　　【Document code】　A　　【Article ID】　1000-5048(2003)02-0125-03
　　Radix AngelicaMorri is the root of A.morri Haya-
ta of genes Angelica(Umbelliferae).It is a Chinese
material medica for local use in Fujian Province , the
leaves of this plant called ”Shanduhuo” for folk use in
Taiwan Province.Study on Property of Chinese Drugs
(Yaoxingkao ,A.D.627 ～ 629)recorded that Radix An-
gelica Morri is rather similar to Radix Gensing with pun-
gent and sweet in taste , and warm in nature , and fit for
diseases of weak was and cold.It is effective in supple-
ment middle-jiao energy , used for diarrhea caused by
deficiency of spleen , and for cough caused by weakness
and chilling.In China , it is ever used as a substitute in
prescriptions for Radix Codonpsis pilosulae[ 1 ,2] .
The pyranocoumarins dilate coronary artery and
lower hypertension as inducer of potassium channel or
antagonist of calcium channel.In 1980s , inducers of
potassium channel were developed into drugs lowering
hypertension as well as protecting cardiac muscle , and
reducing the incidence of coronary artery diseases.Most
of them are compounds with structure of benzopyranes.
In addition , two coumarins with seselin skeleton were al-
so reported to show the same activities〔3〕.No relation-
ships between bioactivities and chemical structures in A.
morri , to our knowledge , have been performed.
1　Experimental
1.1　Materials
MS spectra were run on a:HP5989A instrument.
NMR spectra were recorded on a Bruker ACF-300 in-
strument , TMS was used as an internal standard.IR
spectra were recorded on a Nicolet Impact-410 spec-
trophotometer.UV spectra were carried out on a Shi-
madzu UV-2501PC spectrophotometer.Melting points
were determined on a X4 micromelting point apparatus
and were uncorrected.The specific rotations were
recorded on a PE-241MC polarimeter.Prep.TLC:Sigel
60GF254 ,Chemical Factory of Yantai;LC:Sigel 100-200
mesh and 200-300 mesh , Ocean Chemical Factory of
125
【Received date】　2002-08-02　【＊Corresponding author】　Tel:025-5391239　　Fax:025-5301528　　E-mail:lykong@jlonline.com
Qingdao.Reagents:All reagents were of analytical pure
grade.
The herbal pieces were bought from Fuzhou Co.of
Medicinal Materials in Oct.of 1999 , and authorized by
pharmaceutist Li Liang-guan , Institute of Materia Medi-
ca ,Fujian Province ,P.R.of China.
1.2　Extraction and Isolation
The herbal pieces(19 kg)of Angelica morri were
extracted with 95% EtOH.The concentrated solution
was partitioned with petroleum ether to afford a residue
(98 g).The residue was repeatedly separated on Sigel
columns using petroleum ether-EtOAc as eluent and pu-
rified by recrystallization to yield compounds 1(7 mg),2
(34 mg),3(23 mg), and 4(5 mg).
1.3　Structural Elucidation of Compounds
Compound 1:light yellow needles(petroleum ether-
EtOAc);mp188 ～ 190℃;[ α] 20D +10.5°(c 0.23;
CHCl3), UVλmax 1(MeOH):230(log ε4.23), 252
(4.28), 259(4.28), 296(3.98)nm;IR (KBr):ν
3511 , 1652 , 1622 , 1579 cm-1;EIMS m/z(%):276
(M+ ,74.9),259(6.76), 243(12.20), 205(100.00),
189(9.78), 176(13.20), 43(8.85);1 H-NMR(300
MHz ,CDCl3)δ:1.35 ,1.39(each 3H , s , gem-(CH3)2),
2.33(3H , s , 2- CH3), 2.74 , 2.97(each 1H , dd , J =
17.7 ,5.3Hz , H-4′), 5.41(1H , t , J =5.3Hz , H-3′),
6.00(1H , s ,H-3), 6.33(1H , s ,H-8).13C-NMR spec-
tral data were given in Tab 1.The spectral and physico-
chemical data were the same as those of literature val-
ues[ 4] .Compound 1was identified as 3′R-(+)-hamau-
dol.
Compound 2:yellowish green prism(petroleum
ether-EtOAc);mp 130-130.5℃;[ α] 20D-26.85°(c 0.5;
CHCl3);UVλmax (MeOH):230(log ε4.27), 251
(4.30),258(4.29),296(3.98)nm;IR(KBr):ν2989 ,
1738 ,1648 ,1633 ,1587 ,1579 cm-1;EI-MS m/z(%):
318(M+ , 1.84), 258(21.40), 243(100.00), 205
(10.43), 43(5.71);1H-NMR(300 MHz , CDCl3)δ:
1.34 ,1.36(each 3H , s , gem-(CH3)2), 2.07(3H , s ,
OAc),2.34(3H , s , 2- CH3), 2.78 , 2.98(each 1H , dd ,
J =17.7 , 4.6Hz ,H-4′), 5.11(1H , t , J =4.6 Hz , H-
3′),6.10(1H , s , H-3), 6.34(1H , s , H-8).13C-NMR
spectral data were given in Tab 1.The spectral and
physico-chemical data are the same as those of literature
values[ 5] .Hence , compound 2 is 3′S-(-)-Ο-acetyl-
hamaudol.
Tab 1.13C-NMR data of compounds 1 and 2(CDCl3 ,δ, 75MHz)
Carbon 3′S(-)-Ο-acetylhamaudol(2) 3′R-(+)-hamaudol(1)
C-2 166.8 166.7
C-3 108.4 108.3
C-4 182.5 182.5
C-4a 104.5 104.4
C-5 159.5 159.8
C-6 102.4 102.9
C-7 158.7 158.9
C-8 94.8 94.8
C-8a 156.2 156.3
2- CH3 20.5 20.6
C-2′ 76.8 78.4
C-3′ 69.8 68.8
C-4′ 22.6 25.4
Gem-(CH3) 23.0 , 24.7 22.0 ,24.8
Acetyl- CH3 21.0
C=O 170.3
Compound 3:light yellow needles(petroleum ether-
EtOAc);mp 205.5 ～ 206℃;[ α] 20D 0.00°(c 0.27;
CHCl3).The data of UV , IR , and 1H-NMR are the same
as those of compound 1 ,but no optical value was shown.
Hence compound 3 is a raceme(±)-hamaudol[ 6] , a new
natural product.
Compound 4:colorless needle(EtOH),mp198.5 ～
201℃;[ α] 20D -10.5°(c 0.23;CHCl3).The data of
UV , IR , 1H-NMR are the same as those of compound 1 ,
and it reverses to compound 1 in optical direction.The
spectral and physico-chemical data are the same as those
of 3′S-(-)-hamaudol[ 4 ,5] .
1 .4　Test of inhibitory effect on rat aortic rings
Sprague-Dawley male rats(250 ～ 300 g), supplied
by Animal Center of China Pharmaceutical University.
Thoracic aortas were quickly removed and put into Kreb′s-
Henseleit solution(37.2℃,with 95%O2 and 5%CO2)
(NaCl 118.4 ,KCl 4.7 ,CaCl2 2.5 ,KH2PO4 1.2 ,MgSO4
1.2 ,NaHCO3 25.0 ,Glucose 11.1 mmol/L ,pH=7.4±
0.2;2.5 mmol/L CaCl2 replaced with 1 μl/L EGTA in
no Ca2+ solution)and dissected free of fat and connec-
tive tissue and cut into rings of 4 ～ 6 mm length.One
end of rings was connected to force transducers , rings
126 中 国 药 科 大 学 学 报 　(J Chin Pharm Univ) Vol.34
were equilibrated for 60min under 1g of resting tension.
A maximal response to 80 nmol/L KCl or 2.5 mmol/L
CaCl2 was obtained , and the inhibitory rates were record-
ed at the presence of potent compounds(concentration of
last solution in camber).The tests were repeated for 3
times.Verapamil as contrast was bought from Sigma.
Fig 1.Inhibitory effects of on const riction of rat aortic rings induced by K +
Cardioc active tests showed (-)-3′S-O-acetyl-
hamoudol and(±)-hamaudol possessed inhibitory effects
on constriction of rat aortic rings induced by K+ and
gave the relation of concentration-response(Fig 1), low-
ered that of contrast verapamil.But the contraction in-
duced by Ca2+ was not markedly inhibited when they
were 1.0×10-5 mol/L , the inhibitory rate was 15.9±
1.7 and 7.8±2.0 , respectively.Inhibiting Ca2+ influx
of vascular smooth muscle is one of mechanisms of 3′S-
(-)-O-acetylhamaudol and(±)-hamaudol inhibiting the
contraction of rat aorta.
3′S-(-)-hamaudol was thought to have antihyper-
tensive effect
[ 6] , Komazawa prepared(±)-hamaudol ,
however ,did not give the bioactivity difference between
stereoisomer and racemic mixture , so didn′t here for in-
sufficiency of stereoisomers isolated.Apparently , the
reason of difference from their inhibitory rate which
acetylation or stereoisomer resulted in waits for further
studies.
Acknowledgements
The authors would like to thank the Xin-Zhong New Drug Re-
search and Development Center of China Pharmaceutical University
for the assistance in providing pharmacological facilities.
References
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[ 2] 　Jiangsu New Medicine College.Encyclopedia of Chinese Medica Ma-
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Press ,1977.
[ 3] 　Hata K ,Kozawa M , Baba K , et al.Coumarins from the roots of An-
gelica morri Hayata[ J] .Chem Pharm Bull ,1974 , 22(4):957-961.
[ 4] 　Huang P , Jiang WH , Lai MX , et al.Studies on the chemical con-
stituents of Mashanqianhu(Peucedanum mashanense)[ J] .Chin Tra-
dit Herb Drugs ,1997 , 28(10):579-581.
[ 5] 　Sasaki H ,Taguchi H , Endo T , et al.The constituents of Ledebouriel-
la sseseloides Wolff.I.Structures of three new chromones[ J] .Chem
Pharm Bull , 1982, 30(10):3555-3562.
[ 6] 　Komazawa Y ,Chin M , Hosaka K.Preparation of hamaudol[ P] .JP
62-19589[ 87 19 , 589]
福参活性成分色原酮的研究
孙　视1 , 2 , 许玲玲1 ,孔令义1＊ , 张涵庆2 ,贺善安2
(1中国药科大学天然药物化学教研室 , 南京 210038;2江苏省中国科学院植物研究所 , 南京 210014)
【摘　要】　目的:研究中药福参(Angelica morri Hayata)的活性成分。方法:95%乙醇提取 、石油醚萃取 、硅胶柱层析 、重
结晶等手段提取分离 ,波谱学方法及理化常数对照进行结构鉴定;采用 K+、Ca2+诱导的大鼠主动脉环收缩模型对 3′S-(-)-
Ο-乙酰基亥茅酚和(±)-亥茅酚进行了活性测试。结果:从石油醚部分依次分离到 4 个色原酮类化合物 , 分别为 3′R-(+)-
亥茅酚[ 3′R-(+)-hamaudol] , 3′S-(-)-Ο-乙酰基亥茅酚[ 3′S-(-)-Ο-acetylhamaudol] ,(±)-亥茅酚[(±)-hamaudol] 和 3′S-(-)-亥
茅酚[ 3′S-(-)-hamaudol] 。 3′S-(-)-Ο-乙酰基亥茅酚和(±)-亥茅酚对 K+诱导的高钾模型呈剂量依赖型抑制效应。结论:上
述化合物均为首次从该植物中分离得到 ,(±)-亥茅酚[ (±)-hamaudol] 为一新天然产物;3′S-(-)-Ο-乙酰基亥茅酚和(±)-亥
茅酚通过抑制血管平滑肌细胞外钙内流而起到扩张血管的作用。
【关键词】　福参;色原酮;心血管活性;主动脉环;分离;鉴定
127　No.2 SUN Shi , et al:Chromones dilated rat aorta from Angelica morri Hayata