Studies of coumarins from the Chinese drug qianhu, XXVII: Structure of a new simple coumarin glycoside from Bai-Hua Qianhu, Peucedanum praeruptorum

Article abstract of DOI:10.1248/cpb.56.1349

A new simple coumarin glycoside, named praeroside VI (1), along with six known coumarins, were isolated from an aqueous extract of Bai-Hua Qianhu, the root of Peucedanum praeruptorum DUNN. (Umbelliferae). Spectroscopic analysis and chemical studies were carried out to investigate the structure of the new coumarin, which was concluded to be 1. Additionally, two simple glycosidic coumarins and four simple nonglycosidic coumarins were identified as apiosylskimmin (2), hymexelsin (3), umbelliferone (4), scopoletin (5), isofraxidin (6) and 8-carboxy-7-hydroxy coumarin (7), respectively. This is the first reported identification of compound 7 as a constituent of plant materials.

Full text of DOI:10.1248/cpb.56.1349

September 2008
Notes
Chem. Pharm. Bull. 56(9) 1349—1351 (2008)
1349
1)
Studies of Coumarins from the Chinese Drug Qianhu, XXVII :
Structure of a New Simple Coumarin Glycoside from Bai-Hua Qianhu,
Peucedanum praeruptorum
2)
Hirotaka ISHII, Yoshihito OKADA, Masaki BABA, and Toru OKUYAMA*
Department of Natural Medicine and Phytochemistry, Meiji Pharmaceutical University; 2–522–1 Noshio, Kiyose, Tokyo
2
04–8588, Japan. Received May 9, 2008; accepted June 23, 2008; published online June 25, 2008
A new simple coumarin glycoside, named praeroside VI (1), along with six known coumarins, were isolated
from an aqueous extract of Bai-Hua Qianhu, the root of Peucedanum praeruptorum DUNN. (Umbelliferae). Spec-
troscopic analysis and chemical studies were carried out to investigate the structure of the new coumarin, which
was concluded to be 1. Additionally, two simple glycosidic coumarins and four simple nonglycosidic coumarins
were identified as apiosylskimmin (2), hymexelsin (3), umbelliferone (4), scopoletin (5), isofraxidin (6) and 8-car-
boxy-7-hydroxy coumarin (7), respectively. This is the first reported identification of compound 7 as a constituent
of plant materials.
Key words simple coumarin; Bai-Hua Qianhu; praeroside VI; Peucedanum praeruptorum
The traditional Chinese medicine, Qianhu, which consists owing to the methine proton at H-2ꢂ with an O-functional
of the roots of Peucedanum praeruptorum DUNN. and P. group, which is linked to the methylene groups with signals
decursivum MAXIM. (Umbelliferae), is used for treatment at d 3.18 ppm (1H, dd, Jꢁ14.5, 7.3 Hz) and d 3.14 ppm (1H,
of respiratory disease and pulmonary hypertension. In the dd, Jꢁ14.2, 5.2 Hz). In the sugar proton regions, a doublet
course of our search for the active ingredients of Qianhu, we signal at d 4.15 ppm (1H, d, Jꢁ7.3 Hz) was assigned as an
have reported the structures and biological activities of anomeric proton of D-glucopyranoside linked to the hydroxyl
coumarins isolated from both plants. We isolated the angular group at C-2ꢂ. In addition, the large coupling constant
non-glycosidic pyranocoumarins Pd-Ia, Pd-Ib, Pd-II and Pd- (Jꢁ7.3 Hz) of the anomeric proton revealed a b-linkage in 1.
1
3
III, and the angular glycosidic pyranocoumarins praeroside
These functional groups were also identified by C-NMR
II, praeroside III, praeroside IV and praeroside V, along with spectroscopy. In distortionless enhancement by polarization
linear glycosidic furocoumarin praeroside I, from Bai-Hua transfer (DEPT) experiments, 1 showed eleven oxygenated
Qianhu (Peucedanum praeruptorum DUNN.), and the linear carbons, including six oxymethines at d 103.46 (d, G-1),
non-glycosidic pyranocoumarins Pd-C-I, Pd-C-II, Pd-C-III, 85.94 (d, C-2ꢂ), 77.84 (d, G-5), 77.67 (d, G-3), 74.87 (d, G-
Pd-C-IV, Pd-C-V and AD-I, as well as various saponins, 2), 71.37 (d, G-4) and one oxymethylene at d 62.49 (t, G-6),
3—22)
from Zi-Hua Qianhu, the root of P. decursivum MAXIM.
respectively (see Table 1). Enzymatic hydrolysis of 1 by cel-
In addition, we recently isolated two novel angular pyrano- lulase afforded an aglycone (1a), [a]D ꢀ46.0° (MeOH),
coumarin glycosides, peucedanosides A and B, along with which was identified as (2ꢂR)-7-hydroxy-8-(2ꢂ,3ꢂ-dihydroxy-
23)
24)
25—27)
apterin and praerosides e and f, from Peucedanum 3ꢂ-methylbutyl)-coumarin
praeruptorum DUNN.
with D-glucose.
In this paper, we report the isolation and structure elucida-
tion of a new simple coumarin glycoside and six known sim-
ple coumarins from Bai-Hua Qianhu collected in China.
Results and Discussion
Praeroside VI (1) was isolated as a colorless powder, mp
1
30.5—132.5 °C (decomp.), [a] ꢀ1.0° (MeOH). The mo-
D
lecular formula C H O was determined by high-resolution
2
0
26 10
ꢀ
(HR) EI-MS, m/z 426.1525 ([M] , Calcd 426.1526). A UV
absorption at 326 nm indicated the presence of a coumarin
nucleus. The mass fragmentation pattern (m/z 408, 368, 301,
2
93, 264, 246, 229, 205, 188, 176, 147, 131) was in agree-
ment with the proposed structure 1.
1
The H-NMR spectrum of 1 (Table 1) showed two pairs of
doublets at d 6.17 and 7.81 ppm (each 1H, d, Jꢁ9.5 Hz) and
at d 7.34 (1H, d, Jꢁ8.5 Hz) and 6.81 ppm (1H, d, Jꢁ8.3 Hz)
which were assigned to H-3, H-4, H-5 and H-6 in the
1
coumarin skeleton. The H-NMR spectrum also showed the
presence of one hydroxyl group on a C-7 and C-8-substituted
isopentenyl simple coumarin glycoside fragment, represent-
ing a C-8-(2ꢂ,3ꢂ-dihydroxy-3ꢂ-methylbutyl)-coumarin. The
characteristic signal was at d 4.06 (1H, dd, Jꢁ6.7, 5.5 Hz)
∗
To whom correspondence should be addressed. e-mail: okuyama@my-pharm.ac.jp
© 2008 Pharmaceutical Society of Japan

1
350
Vol. 56, No. 9
1
13
Table 1. H- and C-NMR Spectral Data of Compounds 1 and 1a in CD OD
3
1
13
H
C
1
1a
1
1a
2
3
4
5
6
7
8
9
0
1
1
2
3
163.28 (s)
112.10 (d)
146.08 (d)
128.20 (d)
113.55 (d)
160.37 (s)
114.32 (s)
155.11 (s)
113.38 (s)
26.11 (t)
163.58 (s)
111.67 (d)
146.31 (d)
127.97 (d)
113.92 (d)
161.12 (s)
115.30 (s)
154.88 (s)
113.24 (s)
26.33 (t)
6.17 (1H, d, Jꢁ9.5)
7.81 (1H, d, Jꢁ9.5)
7.34 (1H, d, Jꢁ8.5)
6.81 (1H, d, Jꢁ8.3)
6.18 (1H, d, Jꢁ9.5)
7.84 (1H, d, Jꢁ9.5)
7.34 (1H, d, Jꢁ8.5)
6.84 (1H, d, Jꢁ8.5)
1
ꢂa
ꢂb
ꢂ
3.14 (1H, dd, Jꢁ14.2, 5.2)
3.18 (1H, dd, Jꢁ14.5, 7.3)
4.06 (1H, dd, Jꢁ6.7, 5.5)
3.18 (1H, dd, Jꢁ13.9, 2.4)
2.92 (1H, dd, Jꢁ13.9, 10.3)
3.67 (1H, dd, Jꢁ10.3, 2.4)
85.94 (d)
73.81 (s)
24.70 (q)
26.27 (q)
103.46 (d)
74.87 (d)
77.67 (d)
71.37 (d)
77.84 (d)
62.49 (t)
79.39 (d)
73.86 (s)
25.42 (q)
25.49 (q)
ꢂ
gem-(CH3)2
1.22 (3H, s)
1.29 (3H, s)
1.30 (3H, s)
1.31 (3H, s)
G-1
G-2
G-3
G-4
G-5
G-6a
G-6b
4.15 (1H, d, Jꢁ7.3)
3.15 (1H, dd, Jꢁ9.2, 7.4)
3.18 (1H, dd, Jꢁ9.2, 8.6)
3.26 (1H, dd, Jꢁ9.2, 9.0)
3.10—3.15 (1H, m)
3.61 (1H, dd, Jꢁ12.1, 5.7)
3.76 (1H, dd, Jꢁ11.9, 2.4)
d in ppm from TMS, J value in Hz, r.t.
2
5
The structure of 1 was further established by 2D-NMR
Praeroside VI (1) White powder; mp 130.5—132.5 °C (decomp.), [a]
(log e): 326.0 nm (3.70),
D
1
1
ꢀ1.0° (cꢁ1.0, MeOH). UV (MeOH): l
studies, particularly H– H correlated spectroscopy (COSY),
heteronuclear multiple quantum coherence (HMQC) and nu-
clear Overhauser enhancement and exchange spectroscopy
NOESY). Correlations in HMBC and NOESY revealed pro-
ton–carbon sequences from H-2ꢂ to C-8 and G-C-1, H-1ꢂ to
C-7, C-8 and C-9, respectively.
max
ꢀ
(
MeOHꢀCH CO Na) 376.5 nm. EI-MS (70 eV): m/z (rel. int., %): 426 (M ,
3 2
1
), 408 (2), 264 (26), 247 (38), 246 (34), 229 (29), 205 (64), 176 (100), 175
86). HR-EI-MS: m/z: 426.1525 (Calcd for C H O , 426.1526). H- and
C-NMR: see Table 1.
Enzymatic Hydrolysis of 1 Enzymatic hydrolysis of 1 (20 mg) with
cellulase (20 mg) in H O (5 ml) at 40 °C under stirring for 2 d afforded an
1
(
20 26 10
1
3
(
2
aglycone (1a) and sugar moiety. 1a (4.5 mg) was isolated from n-BuOH sol-
Compounds 2 and 3 are also simple coumarin glycosides.
uble part of reaction mixture.
28)
2
and 3 were identified as apiosylskimmin and hymex-
(
2ꢀR)-7-Hydroxy-8-(2ꢀ,3ꢀ-dihydroxy-3ꢀ-methylbutyl)-coumarin (1a)
elsin by comparison of their structural data with those of White powder; mp 135.0—137.0 °C (decomp.); [a]D ꢀ46.0° (cꢁ0.50,
29)
25
MeOH).
authentic samples.
Apiosylskimmin (2) White powder; mp 197.0—198.0 °C (decomp.);
Nonglycosidic simple coumarins 4, 5, 6, and 7 were identi-
2
5
[
a] ꢃ69.5° (cꢁ1.0, pyridine). UV (MeOH): l (log e): 319.0 nm (4.04);
D max
ꢀ ꢀ ꢀ
3
0)
31)
fied as umbelliferone, scopoletin, isofraxidin, and 8-car-
FAB-MS: m/z: 457 [MꢀH] , 325 [MꢃapiꢀH] , 163 [Mꢃ(apiꢀglc)ꢀH] .
32)
2
5
boxy-7-hydroxy coumarin based on analysis of their physi-
Hymexelsin (3) White powder; [a]D ꢃ104.4° (cꢁ0.50, EtOH); UV
cal and spectral data (MS, H- and C-NMR spectra, H– H (MeOH): lmax (log e): 337.5 nm (3.75), 291.0 nm (3.68); FAB-MS: m/z: 485
1
13
1
1
ꢃ
[
MꢃH] .
COSY, HMQC, HMBC experiments) and by comparison
with literature values.
This is the first reported identification of simple coumarin
Umbelliferone (4) Colorless needles; mp 226.0—227.5 °C (decomp.);
UV (MeOH): l
(log e): 325.5 nm (3.88). EI-MS (70 eV): m/z (rel. int.,
max
ꢀ
%
): 162 (M , 100), 134 (89), 105 (15), 78 (16), 77 (8).
Scopoletin (5) Colorless needles; mp 202.0—203.0 °C (decomp.); UV
MeOH): lmax (log e): 344.0 nm (4.14), 297.5 nm (3.86), 253.5 nm (3.86).
(
7) as a constituent of plant materials.
(
ꢀ
Experimental
General Experimental Procedures Melting points were recorded using (35), 135 (1), 121 (11).
a Yanagimoto melting point apparatus without correction. UV spectra were
Isofraxidin (6) Colorless needles; mp 149.0—150.0 °C (decomp.); UV
EI-MS (70 eV): m/z (rel. int., %): 192 (M , 100), 177 (54), 164 (21), 149
1
13
recorded using Shimadzu 1600. H- and C-NMR spectra were recorded on (MeOH): lmax (log e): 342.0 nm (3.74). EI-MS (70 eV): m/z (rel. int., %):
a JNM-LA 500 spectrometer and a JEOL AL 400. FAB-MS spectra were 222 (M , 100), 207 (25), 194 (15), 179 (18), 161 (5), 151 (10), 149 (4), 133
ꢀ
obtained using a JMS-DX 302 mass spectrometer. Optical rotations were de- (5), 123 (13), 108 (7), 113 (100).
termined for solutions in MeOH using a JASCO DIP-140 polarimeter.
Plant Material Peucedanum praeruptorum DUNN. (Umbelliferae) was
collected from Ringan Town, Zhejiang Province, P. R. China, in August
8-Carboxy-7-hydroxy Coumarin (7) White powder; mp 210 °C (de-
comp.); UV (MeOH): lmax (log e): 333.0 nm (4.03), 258.0 nm (3.50). IR:
KBr
n
max 3600—2600, 1730, 1715, 1610, 1505, 1410, 1360, 1250, 1230,
ꢃ1
ꢀ
2
000 during the flowering season. A voucher specimen was identified by 840 cm . EI-MS (70 eV): m/z (rel. int., %): 206 (M , 7), 188 (23), 162 (97),
Prof. Xiao Luwei at Zhejiang College of Traditional Chinese Medicine and 160 (19), 134 (100), 132 (6), 105 (18), 78 (20), 77 (11).
deposited at the herbarium of Meiji Pharmaceutical University.
Extraction and Isolation Pulverized roots of Peucedanum praerupto-
Acknowledgement The authors are grateful to medical doctor Qian
rum (2.75 kg) were extracted with water under reflux to give 638.6 g of ex- Xiao Hua at Ringan Town Hospital, Zhejiang Province, P. R. China, for sup-
tract. The water extract (638 g) was fractionated with Diaion HP-20 and then port in the collection of Bai-Hua Qianhu, Peucedanum praeruptorum.
HW-40F to give seven fractions, followed by HPLC with ODS (C18) and/or
Develosil (C30) using a MeOH–H O solvent system to yield 1 (98.6 mg), 2 References and Notes
2
(87.7 mg), 3 (6.3 mg), 4 (15.5 mg), 5 (9.7 mg), 6 (3.9 mg) and 7 (23.4 mg).
1) Part XXVI: Okada Y., Ishii H., Zhang Y., Baba M., Okuyama T., Phar-

September 2008
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