全 文 ：【Received date】　2004-11-09
【＊ Corresponding author】　Kong Ling-Yi:Professor , Tel:025-
85391289 , E-mai l:lykong@jlonline.com
Structural Determination of Chromone from Angelica morri
Hayata
SUN Shi1 , 2 ,KONG Ling-Yi 2 ＊ ,ZHANG Han-Qing 1 , HE Shan-An1
1Institute of Botany , Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden Mem.Sun Yat-sen), Nanjing
210014 , China ;
2Department of Natural Medicinal Chemistry , China Pharmaceutical University , Nanjing 210038 , China
【ABSTRACT】　AIM:To study the bioactive constituents of Angelica morri Hayata.METHODS:The constituent was iso-
lated and purified by column chromatography and recrystallization;the structure was identified by spectral analy sis , absolute
configuration was determined based on chemical correlation.RESULT:One chromone was obtained and identified as divari-
catol(1).CONCLUSION:Compound 1 was isolated from Angelica L.for the first time.So far , chromones from Angelica
morri Hayata are similar to bioactive constituents from original plants of Radix Saposhinkoviae , Saposhnikovia diavaricata
Schischkin (Ledebouriella seseloides Wolff).
【KEY WORDS】　Angelica morri Hayata;Divaricatol;Umbelliferae
【CLC Number】　R284.1　　【Document code】　A　　【Ariticle ID】　1672-3651(2005)02-0097-04
　　Angelica morri Hayata is one plant of Umbellifer-
ae , the root is locally used as Fushen in Fujian
Province , the leaf is folkly used as Shanduhuo in Tai-
wan province.In Fuzhou , the root is ever used as a
substitute in prescriptions for Radix Codonpsis pilosu-
lae[ 1 , 2] .Study on Property of Chinese Drugs (Yaox-
ingkao , A.D.627 ～ 629)recorded that Radix Angelica
morri is fit for diseases for weak-ness and cold.It is
used for diarrhea caused by deficiency of spleen , and
for cough caused by weak-ness and chill.Hata et al.
separated 6 constituents from the root [ 3] .On the basis
of previous studies
[ 4-6] , 3′R-(+)-hamoudol , 3′S-(-)-
O-acetylhamaudol , 3′S -(-)-hamaudol , (±)-hamau-
dol , and prim-O-glucosylcimifugin was isolated , anoth-
er chromone-divaricatol(1)was obtained from the root
of Angelica morri Hayata again.
1　Instruments and Experimental
Materials
　　X4 micromelting point apparatus (uncorrected);
PE-241 MC polarimeter;UV-2051 spectrophotometer
(in MeOH);Impact-410 (Nicolet) spectrograph;
Bruker ACF 500MHz and ACF 300MHz spectrometers
(using TMS as an internal standard).Agilent 1100 Se-
ries LC/MSD Trap mass spectrometer;Agilent 110MSD
mass spectrometer.
Roots of Angelica morri Hayata were bought from
Fuzhou Company of Medicinal Materials in October
1999 , and authorized by Pharmaceutist Li Liang-guan ,
Fujian Institute of Materia Medica , China.The voucher
specimen (No.9910003)was deposited in the Institute
of Botany , Jiangsu Province and Chinese Academy of
Sciences.
2　Extraction and Isolation
Powdered roots (19 Kg)were refluxed with 95%
MeOH.The concentrated extract was partitioned succes-
sively between water and petroleum ether (60-90 ℃),
EtOAc , and n-butanol.The EtOAc solution was con-
centrated in vacuo to yield residue (540 g).200 g of
the residue was subjected to column chromatography on
silica gel H , and eluted with a mixture of CHCl3:MeOH
gradually increasing polarity .The fraction (4.5 g)of
CHCl3:MeOH (25∶1)was subjected to column chro-
matography on silica gel H again eluted with petroleum
中国天然药物　2005年 3月　第 3卷　第 2期 Chin J Nat Med　Mar.2005　Vol.3　No.2　97　
ether:acetone(5∶1), and was finally recrystallized with
EtOH to give compound(1)(25 mg , 3.55×10-4%).
3　RESULTS AND DISCUSSION
Compound 1was isolated as colorless needles.The
molecular formula was assigned as C17H18O7 on the basis
of the quasi-molecular ion peak [ M+H] + in the HR-
ESIMS at m/z 335.1141(calcd.335.1125 for C17H19
O7).The UV spectrum showed absorptions at 296 ,
256 , 250 , 228 nm.The IR absorption bands at 3255 ,
1738 , 1658 , 1627 , 1581 , 1442 , and 1147 cm-1 were
attributed to hydroxy , carbon-hydrogen bond , α, β-un-
saturated carbonyl , olefinic band , benzene ring and
carbon-oxygen bond , respectively.
The
1
H NMR spectrum of 1 contained two gem-
methyl signals atδ1.34(3H , s)and 1.36(3H , s),
one methyl signal at δ2.07 which was assigned to the
acetyl group , one methylene signal atδ2.77(1H , dd ,
J =17.8 , 5.1 Hz)and 2.99 (1H , dd , J =17.8 ,
4.7Hz), one hydroxymethyl signal at δ4.55 (2H , d ,
J =5.0 Hz), one methine signal atδ5.11(1H , d , J
=5.0 Hz), two olefinic signals atδ6.21(1H , s)and
6.35 (1H , s), one phenolic hydroxyl signal at δ
12.90.The 13C NMR spectrum and DEPT experiment of
1 confirmed the existence of 17 carbons including 3
methyls , 2 methylenes , 3 methines , and 9 quaternary
carbons.α, β-Unsaturated carbonyl atδ182.5 , acetyl
carbon signals at δ170.3 and δ21.1 , hydroxymethyl
carbon signal at δ61.5 , 8 olefinic carbon signals atδ
95.0 , 102.7 , 104.9 , 106.4 , 155.9 , 159.1 , 159.6
and 167.8 , as well as 2 gem-methyl carbon signals atδ
23.0 and 24.7 were observed.The above spectral evi-
dences indicated that 1 should be a dihydrofurochromone
or a dihydropyrano-chromone contained a pair of gem-
methyl moieties.
In the 1H NMR spectrum one olefinic signal atδ
6.35(s)was assigned to olefinic proton at C-8 , and in
the
13
C NMR spectrum one olefinic carbon signal at δ
95.0 was assigned to olefinic carbon at C-8 combined
with the HMQC spectrum , which indicated the protons
at C-6 and C-7 were substituted.In the HMBC spec-
trum (Figure 2), the signals atδ102.7(C-6), 104.9
(C-4a), and 159.6(C-5)correlated with the phenolic
hydroxyl signal atδ12.90;δ155.9(C-7)and 159.1
(C-8a)correlated withδ6.35(8-H);δ102.7(C-6)
correlated withδ6.35(8-H);δ104.9 (C-4a)corre-
lated withδ6.35(8-H)and 6.21(3-H);δ167.8(C-
2)correlated withδ6.21(3-H).In addition , correla-
tions between H-4′a and H-4′b to C-6;H-4′a and
gem-CH3 to C-3′were observed.The above spectral ev-
idences indicated 1 to be a 2-substituted-5-hydroxy-
chromone contained a dimethyldihydropyran ring.
The HMBC spectrum of 1 showed obvious correlat-
ed peaks:H-3 and 2-CH2 to C-2;H-3 to C-2-CH2 ,
which indicated the proton at C-2 was substituted by hy-
droxymethyl.Acetyl carbon was correlated with H-3′,
which indicated one of H-3 was substituted by one
acetyl.Therefore , the plane structure of 1 was estab-
lished.
Fig 1　Structure and major correlations in HMBC spectrum
of 1
Compound (1)was authenticated to exist in the
methanol extract compared by TLC with two solvent sys-
tems , petroleum ether:acetone (3∶1) and CHCl3:
MeOH(8∶1), which proved that its acetyl did not come
from the solvents used in extract or eluent.So 1 was
confirmed to be a natural product from Angelica morri
Hayata , not an artifact.
Stereochemistry of 1
There is a chiral carbon atom in the molecular
structure.1 was a levo-compound ([ α] 20D-34.6°)and
its absolute configuration was studied further by chemi-
cal correlation with known compound (Figure 2).On
alkaline hydrolysis , one product(2)obtained was iden-
tified by spectral analysis and optical rotation.The ab-
solute configuration at asymmetric carbon of 2 was con-
firmed to be S by comparison of the optical rotatory dis-
persion(ORD)curve with that of hamaudol[ 7] .There-
98　　Chin J Nat Med　Mar.2005　Vol.3　No.2 中国天然药物　2005年 3月　第 3卷　第 2期
fore , the absolute configuration of 1 was decided as S
type.The structure of 1was finally established as divar-
icatol[ 8](Figure 1).The extensive analysis including 1
HNMR, 13CNMR , DEPT , HMQC and HMBC allowed
proton and carbon signals of 1 to be definably assigned
as in Table 1.
Table 1　1H(500MHz , CDCl3)and 13C NMR(125MHz , CDCl3)spectral data of 1
Position δC(DEPT) δH(HMQC) HMBC(C※H)
2 167.8(s) H-3 , 2-CH2
3 106.4(d) 6.21(1H , s)
4 182.5(s) H-3
4a 104.9(s) 5-OH , H-3 , H-8
5 159.6(s) 5-OH
6 102.7(s) 5-OH , H-4′a , H-4′b , H-8
7 155.9(s) H-8
8 95.0(d) 6.35(1H , s)
8a 159.1(s) H-8
2-CH2OH 61.5(t) 4.55(2H , d , J =5.0Hz) H-3
2′ 76.9(s) 2′-gem-CH3
3′ 69.7(d) 5.11(1H , t , J=5.0Hz) 2′-gem-CH3 , H-4′a
4′ 22.6(t) 2.77(1H , dd , J=4.7 , 17.8Hz)
2.99(1H , dd , J=5.1 , 17.8Hz)
2′-CH3 23.0(q) 1.36(3H , s) 2′-CH3
24.7(q) 1.34(3H , s) 2′-CH3
COCH3 170.3(s) CH3 , H-3′
21.1(q) 2.07(3H , s)
OH 12.90(s)
Fig 2　Alkaline hydrolysis of 1
　　Characterization
divaricatol (1):colorless needles , mp 174.5-
177.0 ℃(EtOH), [ α] 20D-34.6°(c 0.01 , CH3OH).
UV(MeOH)λmax 296(log ε3.94), 256(4.27), 250
(4.27), 228(4.21)nm;IR(KBr)ν3255 , 1738 ,
1658 , 1627 , 1581 , 1442 , 1416 , 1323 , 1147 , 1111 ,
848 cm-1;1H NMR(500MHz , CDCl3)and 13C NMR
(125 MHz , CDCl3)see Table 1.HR-ESIMS [ M +
H] + m/z:335.1141 (calcd.335.1125 for C17H19
O7).
Reaction
Alkaline Hydrolysis of 1.Compound (1)(10
mg)was dissolved in 3 ml of EtOH , then added 3%
KOH(3.5 mL)to the solution to react at 70 ℃ for 30
min under stirring.The necessary amount of 1.0 mol/L
H2SO4 was added to adjust to a slightly acidic pH , E-
tOAc(20 mL)was added and the mixture was washed
with water 2 times , and with brine to neutral.The E-
tOAc layer was dried with anhydrous Na2SO4 , then the
solvent was removed in vacuo.The residue was recrys-
tallized with EtOH to afford the product(2)(5.5mg):
lightly yellow needles , mp 175.0-177.0 ℃(EtOH).
[α] 20D-16.2°(c 5.5 ×10-3 , CH3OH).IR (KBr)ν
3390 , 1650 , 1620 , 1570 , 1486 , 1445 , 1380 , 1327 ,
1169 , 1125 cm-1.1HNMR (300 MHz , DMSO-d6)
δ1.34 , 1.37 (each 3H , s , gem-CH3), 2.46 (1H ,
dd , J =17.4 , 7.0Hz , H-4′a), 2.95 (1H , dd J =
17.4 , 5.4 Hz , H-4′b), 3.72(1H , dd , J =7.0 , 5.4
Hz , H-3′), 4.38 (2H , d , J =5.1 Hz , 2-CH2-),
6.21(1H , s , 3-H), 6.27(1H , s , 8-H), 4.46(1H ,
中国天然药物　2005年 3月　第 3卷　第 2期 Chin J Nat Med　Mar.2005　Vol.3　No.2　99　
s , 3′-OH), 5.25(1H , t , J =5.1Hz , 2-CH2-OH),
13.00(1H , s , 5-OH).
Refernces
[ 1] 　Institute of Botany , Jiangsu Province , et al.Compendium of New
China(Xinhua)Herbal , Vol.1.Shanghai:Shanghai Sciences and
Technology Press , 1988 , 344.
[ 2] 　Kan WS.Manual of Medicinal Plants in Taiwan [ M] , Vol.3.
Taipei:National Research Institute of Chinese Medicines , 1985 ,
646.
[ 3] 　Hata K , Kozawa M , Baba K , et al.Coumarins from the roots of
Angelica morri Hayata[ J] .Chem Pharm Bull , 1974 , 22(4):957-
961.
[ 4] 　Sun S , Shi YR, Kong LY , et al.Glycosides f rom Angelica morri
Hayata , Chin Tradit HerbDrugs , 2003 , 34(8):682-684.
[ 5] 　Sun S , Xu LL , Kong LY , et al.Chromones from Angelica.morri
Hayata., J China Pharm Univ , 2003 , 35(2):125-127.
[ 6] 　Sun S , Liu B , Kong LY , et al.Chemical study on Angelica.morri
Hayata.J China Pharm Univ , 2002 , 33(3):181-183.
[ 7] 　Baba K , Hata K , Kimura Y , et al.Chemical studies of Angelica
japonica A.Gray.I.on the constituents of ethyl acetate extract of
the root.Chem Pharm Bul l , 1981 , 1981(9):2565-2570.
[ 8] 　Okuyama E, Hasegawa T , Matsushita T , et al.Analgesic compo-
nents of saposhnikovia root (Saposhnikovia diavaricata).Chem
Pharm Bull , 2001 , 49(2):154-160.
福参(Angelica morri Hayata)色原酮化合物的结构确定
孙　视1 , 2 ,孔令义2＊ ,张涵庆1 ,贺善安1
1江苏省中国科学院植物研究所(南京中山植物园), 南京 210014;
2中国药科大学天然药物化学教研室 ,南京 210038
【摘　要】　目的:研究福参的活性成分。方法:采用柱色谱及重结晶法进行分离纯化 , 通过光谱法进行结构鉴定 , 化
学沟通法确定绝对构型。结果:分得一个色原酮 divaricatol(1)。结论:化合物 1 首次从当归属植物中分得。到目前为止 ,
福参中分离到的色原酮类化合物与中药防风的基源植物防风(Saposhnikovia diavaricata Schischk.Syn.Ledebouriella seseloides
Wolff)中的色原酮活性成分很相近。
【关键词】　福参;divaricatol;伞形科
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100　　Chin J Nat Med　Mar.2005　Vol.3　No.2 中国天然药物　2005年 3月　第 3卷　第 2期