Lignans from the roots of Saururus chinensis

Article abstract of DOI:10.1021/np8002723

Four new lignans, saucerneol F (1), saucerneol G (2), saucerneol H (3), and saucerneol I (4), were isolated from the EtOAc extract of the roots of Saururus chinensis, together with one known compound, saucerneol D (5). The structures of compounds 1-4 were

Full text of DOI:10.1021/np8002723

J. Nat. Prod. 2008, 71, 1771–1774
1771
Lignans from the Roots of Saururus chinensis
Chang-Seob Seo,†, Ming-Shan Zheng,†, Mi-Hee Woo,‡ Chong-Soon Lee,§ Sung-Ho Lee,† Byeong-Seon Jeong,†
Hyeun-Wook Chang,† Yurngdong Jahng,† Eung-Seok Lee,† and Jong-Keun Son*,†
College of Pharmacy, Yeungnam UniVersity, 214-1 Dae-dong, Gyeongsan, Korea, 712-749, College of Pharmacy, Catholic UniVersity of
Daegu, 330 Geumnak 1-ri, Gyeongsan, Korea, 712-702, and Department of Biochemistry, College of Science, Yeungnam UniVersity,
214-1 Dae-dong, Gyeongsan, Korea, 712-749
ReceiVed May 2, 2008
Four new lignans, saucerneol F (1), saucerneol G (2), saucerneol H (3), and saucerneol I (4), were isolated from the
EtOAc extract of the roots of Saururus chinensis, together with one known compound, saucerneol D (5). The structures
of compounds 1-4 were elucidated by spectroscopic analysis. These compounds showed cytotoxic activities against
HT-29, MCF-7, and HepG-2 cell lines.
Saururus chinensis (Saururaceae) is a perennial herbaceous plant
that has been used in the treatment of various diseases such as
edema, jaundice, gonorrhea, fever, and inflammation in Korean folk
medicine.1 Studies of the genus Saururus have shown the presence
of lignans,2-5 aristolactams, flavonoids, anthraquinones, and
fruanoditerpenes,10-13 some of which exhibited neuroleptic,6
hepatoprotective,7 antifeedant,8 and antioxidant activities.9 Previ-
ously, we reported the isolation of protective agents against sepsis
in the animal model from this plant.14 In this paper, we report the
isolation and structural determination of five lignans, as well as
their cytotoxic activity against human colon adenocarcinoma (HT-
29), human breast adenocarcinoma (MCF-7), and human liver
hepatoblastoma (HepG-2) cell lines.
The MeOH extract of the roots of S. chinensis was partitioned
by n-hexane, EtOAc, BuOH, and H2O successively. The EtOAc
extract was chromatographed on silica gel, Sephadex LH-20, and
reversed-phase columns to afford five lignans (1-5). Compound 5
was identified as the known compound saucerneol D by comparison
15
1
of the H and 13C NMR data and the specific rotation value.
Compound 1 was obtained as an amorphous, brown powder, with
a molecular formula of C30H32O8 determined by HRFABMS (m/z
found 543.2000 [M + Na]+; calcd 543.1995). The UV and IR
spectra of 1 revealed the presence of hydroxy (3468 cm-1) and
Figure 1. Key HMBC correlations of compounds 1-4.
UV spectrum showed maxima at 229, 276, and 306 nm, indicating
an aromatic phenolic ketone moiety in 2. The IR spectrum of 2
revealed the presence of hydroxy (3424 cm-1) and conjugated
ketone groups (1658 cm-1). The 1H NMR spectrum exhibited two
distinct sec-methyls (H-9′ and H-9), two methines (H-8′ and H-8),
benzylic methylene signals (H-7b′ and H-7a′), two methylenedioxy
groups, and five aromatic protons (H-2, H-5, H-6, H-3′, and H-6′).
The 1H and 13C NMR spectra showed two separate sets of aromatic
carbon atoms, one due to a 3,4-methylenedioxy moiety, the other
due to a 2′-hydroxy-4′,5′-methylenedioxyphenyl unit. In the HMBC
spectrum of 2, long-range correlations of C-7 with H-2, H-6, H-8,
and H-9 were observed (Figure 1). In the NOESY spectrum of 2,
H-9′ showed a correlation with 6′-H but not with H-3′. On the basis
of these data, 2 was determined as 1-(benzo[d][1,3]dioxol-5-yl)-
4-(6-hydroxybenzo[d][1,3]dioxol-5-yl)-2,3-dimethylbutan-1-one and
named saucerneol G.
The molecular formula of 3 was found to be C20H22O6 by
HREIMS (m/z found 340.1316 [M - H2O]+; calcd 340.1311). The
IR and UV spectra of 3 revealed the presence of hydroxy (3424
cm-1) and phenolic groups (1504 cm-1, 231 and 290 nm). The 1H
NMR spectrum showed the presence of two methyl doublets (H-9
and H-9′), two methine groups (H-8′ and H-8), one benzylic
methylene (H-7b′ and H-7a′), one benzylic methine group substi-
tuted by oxygen (H-7), two methylenedioxy groups, and five
aromatic protons (H-2, H-5, H-6, H-3′, and H-6′). The 2D 1H-1H
COSY spectrum indicated coupling among H-7, H-8, H-9, H-7′,
H-8′, and H-9′. The 1H and 13C NMR spectra showed two separate
1
oxygenated phenyl groups (234 and 284 nm, 1505 cm-1). The H
and 13C NMR spectra of 1 were similar to those of 5, but lacked
the signals of two methoxy groups of 5 and, instead, showed the
signal of one additional methylenedioxy group (δH 5.964, 2H, δC
101.2). Slight differences of chemical shifts at C-1′′, C-2′′, C-3′′,
C-4′′, C-5′′, and C-6′′ were found in the 0.05-3 ppm range,
respectively, in the 1H and 13C NMR spectra of 1 from those of 5.
DEPT, HMQC, HMBC, and NOESY spectra of 1 established the
one-dimensional structure (Figure 1). The specific rotation of 1
{[R]25 -60.6 (c 0.2, CHCl3)} exhibited the same sign as that of
D
5 {[R]25 -88.1 (c 1.2, CHCl3)}. The relative configuration of 1
D
could be deduced by comparison with literature data for related
lignans (Supporting Information).15-29 From the above evidence,
1 was determineded as threo-1-(benzo[d][1,3]dioxol-5-yl)-2-[4-
{(2R,3R,4ꢀ,5ꢀ)-5-(benzo[d][1,3]dioxol-5-yl)-3,4-dimethyltetrahy-
drofuran-2-yl}-2-methoxyphenoxy]propan-1-ol and named saucer-
neol F.
The molecular formula of 2 was found to be C20H20O6 by
HRFABMS (m/z found 357.1335 [M + H]+; calcd 357.1338). The
* To whom correspondence should be addressed. Tel: 82-53-810-2817.
Fax: 82-53-810-4654. E-mail: jkson@yu.ac.kr.
† College of Pharmacy, Yeungnam University.
‡ Catholic University of Daegu.
§ Department of Biochemistry, Yeungnam University.
These authors contributed equally to this work.
10.1021/np8002723 CCC: $40.75
2008 American Chemical Society and American Society of Pharmacognosy
Published on Web 10/08/2008

1772 Journal of Natural Products, 2008, Vol. 71, No. 10
Notes
1
Table 1. Characteristic H NMR Data of Mosher Esters of 3 for
Determination of Absolute Configuration
position
7
8
9
8′
9′
3S (δS)
5.49
5.46
S
1.82
1.91
-0.09
0.30
0.42
-0.12
1.68
2.02
-0.34
0.55
0.63
-0.08
3R (δR)
∆δ (δS - δR)
1
Table 2. Characteristic H NMR Data of Mosher Esters of 4 for
Determination of Absolute Configuration
position
7
9
7′
8′
9′
4S (δS)
5.57
5.60
S
0.68
0.63
-0.05
4.26
4.15
-0.11
2.14
1.76
-0.38
0.57
0.46
-0.11
4R (δR)
∆δ (δS - δR)
galbacin, which possesses a 7S,8S,8′S,7′S configuration, and the
specific rotation value of 4a showed the same sign as (-)-galbacin,
[R]22D -41.5 (c 0.026, CHCl3) {[R]D -11.7}.4,28,34 On the bais of
this evidence, 4 was suggested to be (1S,2S,3S,4S)-1,4-di(benzo-
[d][1,3]dioxol-5-yl)-2,3-dimethylbutane-1,4-diol and named sau-
cerneol I.
Compounds 1-5 and the positive control, camptothecin, exhib-
ited cytotoxic activities against the HT-29 cell line (IC50 values of
10, 55, 53, 21, 13, and 2 µM, respectively), the hepG-2 cell line
(IC50 values of 11, 62, 61, >100, 16, and 0.3 µM, respectively),
and the MCF-7 cell line (IC50 values of >100, 64, 72, >100, >100,
and 10 µM, respectively).
sets of aromatic carbon atoms, one due to a 3,4-methylenedioxy
moiety, the other due to a 2′-hydroxy-4′,5′-methylenedioxyphenyl
unit. In the NOESY spectrum of 3, H-9′ showed a correlation with
6′-H but not with H-3′. From the HMBC spectrum of 3, the one-
dimensional structure of 3 was determined to be the 2′-hydroxy
derivative of the reported compound 6 (Figure 1).30 The absolute
configuration at C-7 of 3 was established by Mosher ester
methodology.31-33 The differences of chemical shift values obtained
by subtracting (R)-MTPA ester from (S)-MTPA ester [∆δH (δS -
δR)] are shown in Table 1, and the negative values of ∆δH (δS -
δR) at H-8, 9, 8′, and 9′ suggested a 7S configuration in compound
3. To determine the configurations at C-8 and C-8′, 3 was converted
to an aryltetralin type compound (3a) with acetyl chloride by the
reported reaction, in which inversion of the configuration at C-7
of 6 to that of 6a was shown.30 The pattern of cyclization of 3a
was confirmed by a 1D-NOE experiment, which demonstrated
correlations of acetyl protons to both 3′-H and 7′-H. The observed
coupling constants, J7,8 ) 9.2 Hz and J7′,8′ ) 10.9 Hz, for 3a
indicated all-axial orientations of H-7, H-8, H-7′, and H-8′ and
confirmed the all-trans arrangement of the two methyl groups and
the pendant phenyl group with all pseudo-equatorial positions. On
the basis of this evidence, the structure of 3 was proposed to be
6-{(2S,3R,4S)-4-(benzo[d][1,3]dioxol-5-yl)-4-hydroxy-2,3-
dimethylbutyl}benzo[d][1,3]dioxol-5-ol, and 3 was named saucer-
neol H.
Experimental Section
General Experimental Procedures. Melting points were measured
using the capillary melting point apparatus, Electrothermal 9100 (Essex,
UK), and are uncorrected. Optical rotations were measured using a
JASCO DIP-1000 (Tokyo, Japan) automatic digital polarimeter. FT-
IR spectra were recorded on a JASCO FT-IR 300E (Tokyo, Japan)
spectrophotometer and UV spectra on a JASCO V-550 (Tokyo, Japan)
1
spectrophotometer. H NMR (250, 600, and 900 MHz) and 13C NMR
(62.9 and 150 MHz) were recorded on a Bruker AMX250, DMX600,
and Bruker Biospin Avancell 900 spectrometer (Karlsruhe, Germany).
Samples were dissolved in CDCl3 and reported in ppm downfield from
TMS. HIFABMS and HIEIMS were obtained on a JEOL JMS700
spectrometer (JEOL, Japan). The stationary phases used for column
chromatography (silica gel 60, 70-230 and 230-400 mesh, and
Lichroprep RP-18 gel, 40-63 µm, Merck) and TLC plates (silica gel
60 F254 and RP-18 F254s, 0.25 mm, Merck) were purchased from Merck
KGaA (Darmstadt, Germany). Spots were detected under UV radiation
and by spraying with 10% H2SO4, followed by heating. (R)-(-)-R-
Methoxy-R-(trifluoromethyl)phenylacetyl chloride [(R)-MTPA-Cl] and
(S)-(+)-R-methoxy-R-(trifluoromethyl)phenylacetyl chloride [(S)-MTPA-
Cl] were purchased from Aldrich (St. Louis, MO; purity 99.0%).
Plant Material. The roots of S. chinensis were purchased in February
2003 from a folk medicine market, “Yak-ryong-si”, in Daegu, Republic
of Korea. These materials were confirmed taxonomically by Professor
Gi-Hwan Bae, Chungnam National University, Daejeon, Korea. A
voucher specimen (YNSC2004) has been deposited at the College of
Pharmacy, Yeungnam University.
1
The H and 13C NMR spectra of 4 showed signals of only 10
protons and 10 carbons, and the high-resolution mass spectrum
confirmed its molecular formula as C20H20O6, which indicated the
symmetric feature of this compound. The 1H and 13C NMR spectra
of 4 suggested the presence of two 3,4-methylenedioxy phenyl units
and an 8,8′-dimethyl-7,7′-diol-type skeleton. To determine the
absolute configuration of C-7, Mosher ester derivatives (4R and 4S)
Extraction and Isolation. The dried roots of S. chinensis (9.7 kg)
were extracted with 70% MeOH (×3) by refluxing for 24 h, and the
MeOH solution was then evaporated to dryness (1.0 kg). The MeOH
extract was suspended in H2O (1.4 L), and the resulting H2O layer
was successively partitioned with n-hexane, EtOAc, and BuOH (each
1.4 L × 3). The EtOAc extracts (130 g) were loaded onto a silica gel
column (12 × 100 cm, 70-230 mesh) and eluted by a stepwise gradient
of n-hexane-EtOAc (100:0 f 0:100) and then EtOAc-MeOH (100:0
f 0:100). The eluates (500 mL in each flask) were combined into 39
fractions (SCE1-SCE39) on the basis of silica gel TLC. Fractions 25
(1.3 g) and 28 (1.4 g) were chromatographed on a reversed-phase
column (4 × 50 cm, LiChroprep RP-18), using MeOH-H2O (gradient
elution, from 50:50 to 100% MeOH), to give 1 (230 mg) and 4 (140
mg), respectively. Fractions 20 (1.3 g) and 26 (1.0 g) were subjected
1
of 4 were prepared, and H NMR data of 4R and 4S were also
assigned on the basis of the 1H-1H-COSY spectra (Table 2). The
negative values of ∆δH (δS - δR) at H-9, 7′, 8′, and 9′ suggested
a 7S configuration for compound 4. To determine the configurations
at C-8 and C-8′, 4 was converted to a tetrahydrofuran-type
compound (4a) by treatment with acetyl chloride.30 1H and 13C
NMR data of 4a were in excellent accordance with those of (-)-

Notes
Journal of Natural Products, 2008, Vol. 71, No. 10 1773
to reversed-phase column chromatography (4 × 50 cm, LiChroprep
RP-18), using MeOH-H2O (gradient elution, from 40:60 to 100%
MeOH), to give 2 (70 mg) and 3 (40 mg), respectively. Fraction 29
(500 mg) was chromatographed on a Sephadex LH-20 column (4.5 ×
80 cm, Sephadex LH-20) eluted with MeOH (3.0 L) to give 5 (400
mg).
OCH2O-3,4), 50.1 (CH, C-7), 44.8 (CH, C-8), 34.6 (CH, C-8′), 32.9
(CH2, C-7′), 20.9 (CH3, ArCOOCH3), 19.9 (CH3, C-9′), 16.8 (CH3,
C-9).
Saucerneol I (4): white powder (MeOH-H2O); mp 138-142 °C;
[R]25 -70.3 (c 0.20, CHCl3); UV (MeOH) λmax (log ε) 235 (4.07),
D
287 (4.00) nm; IR (KBr) νmax 3333, 2968, 2919, 1503, 1488, 1443,
1248, 1040 cm-1; 1H NMR (CDCl3, 250 MHz) δ 6.86 (2H, s, H-2, 2′),
6.77 (2H, d, J ) 8.8 Hz, H-6, H-6′), 6.73 (2H, d, J ) 8.1 Hz, H-5,
H-5′), 5.92 (4H, s, OCH2O × 2), 4.26 (2H, d, J ) 9.9 Hz, H-7, H-7′),
2.44 (2H, m, H-8, H-8′), 0.56 (6H, d, J ) 6.7 Hz, H-9, H-9′); 13C
NMR (CDCl3, 62.9 MHz) δ 147.8 (C, C-3, C-3′), 147.0 (C, C-4, C-4′),
138.4 (C, C-1, C-1′), 120.5 (CH, C-6, C-6′), 107.9 (CH, C-5, C-5′),
107.0 (CH, C-2, C-2′), 100.9 (CH2, OCH2O × 2), 77.1 (CH, C-7, C-7′),
39.1 (CH, C-8, C-8′), 10.4 (CH3, C-9, C-9′); HREIMS m/z 358.1414
[M]+ (calcd for C20H21O5, 358.1416).
Saucerneol F (1): amorphous, brown powder (EtOAc-MeOH); mp
59-61 °C; [R]25D -60.6 (c 0.2, CHCl3); UV (MeOH) λmax (log ε) 234
(4.36), 284 (4.12) nm; IR (KBr) νmax 3468, 2963, 2891, 1505, 1443,
1249, 1038 cm-1; 1H NMR (CDCl3, 900 MHz) δ 6.98 (1H, d, J ) 8.1
Hz, H-5′), 6.92 (1H, br s, H-2′′), 6.89 (1H, br s, H-2′), 6.86 (1H, d, J
) 7.2 Hz, H-6′′), 6.82 (1H, br s, H-2), 6.82 (1H, br d, J ) 6.7 Hz,
H-6′), 6.80 (1H, d, J ) 7.9 Hz, H-5), 6.78 (1H, d, J ) 8.0 Hz, H-5′′),
6.76 (1H, br d, J ) 7.8 Hz, H-6), 5.964 (2H, s, OCH2O-3,4), 5.955
(2H, s, OCH2O-3′′,4′′), 5.43 (1H, d, J ) 6.8 Hz, H-7′), 5.42 (1H, d, J
) 6.9 Hz, H-7), 4.62 (1H, d, J ) 8.4 Hz, H-7′′), 4.10 (1H, dq, J ) 8.1,
6.3 Hz, H-8′′), 3.93 (3H, s, OCH3), 2.28 (1H, ddq, J ) 13.6, 6.8, 6.8
Hz, H-8′), 2.26 (1H, ddq, J ) 13.6, 6.8, 6.8 Hz, H-8), 1.16 (3H, d, J
) 6.2 Hz, H-9′′), 0.71 (3H, d, J ) 6.8 Hz, H-9), 0.70 (3H, d, J ) 6.8
Hz, H-9′); 13C NMR (CDCl3, 150 MHz) δ 150.8 (C, C-3′), 147.9 (C,
C-3′′), 147.7 (C, C-4′′), 147.6 (C, C-3), 146.6 (C, C-4), 146.5 (C, C-4′),
136.9 (C, C-1′), 135.6 (C, C-1), 134.2 (C, C-1′′), 121.3 (CH, C-6′′),
119.5 (CH, C-6), 119.1 (CH, C-5′), 118.9 (CH, C-6′), 110.3 (CH, C-2′),
108.3 (CH, C-5′′), 108.0 (CH, C-5), 107.8 (CH, C-2′′), 107.1 (CH,
C-2), 101.2 (CH2, OCH2O-3,4), 101.1 (CH2, OCH2O-3′′,4′′), 84.2 (CH,
C-8′′, 83.9 (CH, C-7), 83.7 (CH, C-7′), 78.6 (CH, C-7′′), 56.0 (CH3,
OCH3), 44.1 (CH, C-8), 44.0 (CH, C-8′), 17.1 (CH3, C-9′′), 14.9 (CH3,
C-9, C-9′); HRFABMS m/z 543.2000 [M + Na]+ (calcd for
C30H32O8Na, 543.1995).
(-)-Galbacin (4a): [R]25D -41.5 (c 0.03, CHCl3); 1H NMR (CDCl3,
250 MHz) δ 6.89 (2H, s, H-2, H-2′), 6.82 (2H, d, J ) 7.9 Hz, H-6,
H-6′), 6.76 (2H, d, J ) 7.9 Hz, H-5, H-5′), 5.92 (4H, s, OCH2O × 2),
4.59 (2H, d, J ) 8.9 Hz, H-7, H-7′), 1.72 (2H, m, H-8, H-8′), 1.01
(6H, d, J ) 5.7 Hz, H-9, H-9′); 13C NMR (CDCl3, 62.9 MHz) δ 147.7
(C, C-3, C-3′), 146.9 (C, C-4, C-4′), 136.3 (C, C-1, C-1′), 119.7 (CH,
C-6, C-6′), 107.9 (CH, C-5, C-5′), 106.6 (CH, C-2, C-2′), 100.9 (CH2,
OCH2O × 2), 88.3 (CH, C-7, C-7′), 51.0 (CH, C-8, C-8′), 13.8 (CH3,
C-9, C-9′).
Preparation of (S)- and (R)-MTPA Esters of 3 and 4. Mosher’s
esters were prepared according to the reported method.31-33 To
compound 3 (3 mg) in 0.5 mL of CH2Cl2 were added sequentially 0.2
mL of anhydrous pyridine, 0.5 mg of 4-(dimethylamino)pyridine, and
12.5 mg of (R)-(-)-R-methoxy-R-(trifluoromethyl)phenylacetyl chloride
[(R)-MPTA-Cl]. The mixture was left at room temperature overnight
and checked by TLC to determine if the reaction was completed. After
addition of 1 mL of n-hexane, the reaction mixture was passed through
a column (6 × 0.6 cm, silica gel, 230-400 mesh, 9385) with
n-hexane-CH2Cl2 (1:2). The eluate was dried in Vacuo to give the
(S)-MTPA ester of 3. Using (S)-MTPA-Cl, the (R)-MTPA ester of 3
was prepared. The same procedure was repeated with 4 (5 mg) to give
the (S)- and (R)-MTPA esters of 4.
Conversion of 3 and 4 to 3a and 4a. Compounds 3 (6 mg) and 4
(5 mg) were each dissolved in acetyl chloride (3 drops). The solutions
were kept at room temperature for 2 h and, after the addition of H2O,
neutralized with aqueous NaHCO3 and extracted with CH2Cl2. The
organic layer was dried (Na2SO4), filtered, and evaporated. The residue
that dissolved in CH2Cl2 (1-2 mL) was passed through a column (6
× 0.6 cm, silica gel, 230-400 mesh, 9385) with a CH2Cl2 mobile phase.
The eluates were dried in Vacuo to give compounds 3a (3 mg) and 4a
(2 mg).
Cytotoxicity Bioassays. A tetrazolium-based colorimetric assay
(MTT assay) was used to determine the cytotoxicities toward human
colon adenocarcinoma (HT-29), human breast adenocarcinoma (MCF-
7), and human liver hepatoblastoma (HepG-2) cell lines.35
Saucerneol G (2): amorphous, brown powder (MeOH-H2O); mp
41-43 °C; [R]22D +13 (c 0.59, CHCl3); UV (MeOH) λmax (log ε) 229
(4.14), 276 (3.69), 306 (3.88) nm; IR (KBr) νmax 3424, 2954, 2903,
1658, 1504, 1442, 1251, 1173, 1038 cm-1; 1H NMR (CDCl3, 250 MHz)
δ 7.59 (1H, dd, J ) 8.2 1.5 Hz, H-6), 7.45 (1H, d, J ) 1.5 Hz, H-2),
6.86 (1H, d, J ) 8.2 Hz, H-5), 6.49 (1H, s, H-3′), 6.48 (1H, s, H-6′),
6.04 (2H, s, OCH2O), 5.84 (2H, s, OCH2O), 3.17 (1H, m, H-8), 2.60
(1H, d, J ) 13.5 Hz, H-7a′), 2.15 (1H, m, H-8′), 2.00 (1H, dd, J )
13.5, 10.1 Hz, H-7b′), 1.21 (3H, d, J ) 7.2 Hz, H-9), 0.97 (3H, d, J )
6.4 Hz, H-9′); 13C NMR (CDCl3, 62.9 MHz) δ 204.7 (C, C-7), 152.2
(C, C-3), 149.9 (CH, C-5′), 148.3 (C, C-4), 146.7 (C, C-4′), 140.3 (C,
C-1′), 130.6 (C, C-1), 125.1 (CH, C-6), 117.4 (C, C-2′), 110.1 (CH,
C-6′), 108.5 (CH, C-2), 108.0 (CH, C-5), 102.0 (CH2, OCH2O), 100.8
(CH2, OCH2O), 98.6 (CH, C-3′), 46.3 (CH, C-8), 37.7 (CH2, C-7′),
35.6 (CH, C-8′), 16.5 (CH3, C-9), 16.2 (CH3, C-9′); HRFABMS m/z
357.1335 [M + H]+ (calcd for C20H21O6, 357.1338).
Saucerneol H (3): sticky solid (MeOH-H2O); [R]22D -51.9 (c 0.35,
CHCl3); UV (MeOH) λmax (log ε) 231 (4.10), 290 (3.93) nm; IR (KBr)
ν
max 3424, 2954, 2903, 1658, 1504, 1442, 1251, 1173, 1038 cm-1; 1H
NMR (CDCl3, 250 MHz) δ 6.80 (1H, s, H-2), 6.72 (2H, s, H-5, H-6),
6.52 (1H, s, H-6′), 6.33 (1H, s, H-3′), 5.93 (2H, s, OCH2O), 5.84 (2H,
s, OCH2O), 4.27 (1H, d, J ) 9.7 Hz, H-7), 2.81 (1H, dd, J ) 13.3, 3.8,
H-7a′), 2.25 (1H, m, H-7b′), 2.18 (1H, m, H-8′), 1.74 (1H, m, H-8),
0.85 (3H, d, J ) 6.5 Hz, H-9′), 0.56 (3H, d, J ) 7.0 Hz, H-9); 13C
NMR (CDCl3, 62.9 MHz) δ 148.7 (C, C-5′), 147.8 (C, C-3), 147.1 (C,
C-4), 146.2 (C, C-4′), 140.7 (C, C-1′), 138.0 (C, C-1), 120.6 (CH, C-6),
119.0 (C, C-2′), 110.3 (CH, C-6′), 108.0 (CH, C-5), 107.0 (CH, C-2),
101.0 (CH2, OCH2O), 100.8 (CH2, OCH2O), 98.4 (CH, C-3′), 79.5 (CH,
C-7), 43.1 (CH, C-8), 38.0 (CH2, C-7′), 34.0 (CH, C-8′), 14.6 (CH3,
C-9′), 12.0 (CH3, C-9); HREIMS m/z 340.1316 [M - H2O]+ (calcd
for C20H21O5, 340.1311).
Acknowledgment. This work was supported by a Korean Research
Foundation Grant (KRF-2006-005-J01101).
Supporting Information Available: NMR data of 1, 2, 3, 4, 3a,
and 4a. This material is available free of charge via the Internet at
http://pubs.acs.org.
References and Notes
(1) Chung, B. S.; Shin, M. G. Dictionary of Korean Folk Medicine; Young
Lim Sa: Seoul, 1990; p 813.
(7S,8R,9R)-9-(Benzo[d][1,3]dioxol-5-yl)-7,8-dimethyl-6,7,8,9-tet-
(2) Rao, K. V.; Alvarez, F. M. J. Nat. Prod. 1982, 45, 393–397.
(3) Rao, K. V.; Alvarez, F. M. J. Nat. Prod. 1983, 48, 592–597.
(4) Rao, K. V.; Rao, N. S. P. J. Nat. Prod. 1990, 53, 212–215.
(5) Chattopadhyay, S. K.; Rao, K. V. Tetrahedron 1987, 43, 669–678.
(6) Rao, K. V.; Puri, V. N.; Diwan, P. K.; Alvarez, F. M. Pharmacol.
Res. Commun. 1987, 19, 629–638.
(7) Sung, S. H.; Kim, Y. C. J. Nat. Prod. 2000, 63, 1019–1021.
(8) Kubanek, J.; Fenical, W.; Hay, M. E.; Brown, P. J.; Lindquist, N.
Phytochemistry 2000, 54, 281–287.
rahydronaphtho[2,1-d][1,3]dioxol-5-yl acetate (3a): [R]28 +5.8 (c
D
0.03, CHCl3); 1H NMR (CDCl3, 250 MHz) δ 6.70 (1H, d, J ) 7.9 Hz,
H-5), 6.61 (1H, dd, J ) 8.0, 1.5 Hz, H-6), 6.55 (1H, d, J ) 1.4 Hz,
H-2), 6.42 (1H, s, H-3′), 5.89 (2H, s, OCH2O-3,4), 5.68 and 5.58 (each
1H, d, J ) 1.4 Hz, OCH2O-4′,5′), 3.44 (1H, d, J ) 9.2 Hz, H-7), 2.63
(1H, dd, J ) 15.9, 3.3 Hz, H-7a′), 2.30 (3H, s, ArCOOCH3), 2.17 (1H,
dd, J ) 15.9, 10.9 Hz, H-7b′), 1.43 (2H, m, H-8, H-8′), 1.03 (3H, d,
J ) 6.0 Hz, H-9′), 0.93 (3H, d, J ) 6.0 Hz, H-9); 13C NMR (CDCl3,
62.9 MHz) δ 169.7 (C, CH3-CO2Ar), 147.2 (C, C-4′), 145.5 (C, C-5′),
145.3 (C, C-3), 143.4 (C, C-4), 141.3 (C, C-1), 139.5 (C, C-6′), 123.2
(C, C-1′), 122.8 (C, C-2′), 122.0 (CH, C-6), 108.9 (CH, C-2), 107.5
(CH, C-5), 101.6 (CH, C-3′), 101.1 (CH2, OCH2O-4′,5′), 100.7 (CH2,
(9) Rajbhandari, I.; Takamatsu, S.; Nagle, D. G. J. Nat. Prod. 2001, 64,
693–695.
(10) Rao, K. V.; Reddy, G. C. S. J. Nat. Prod. 1990, 53, 309–312.
(11) Wang, E. C.; Shih, M. H.; Liu, M. C.; Chen, M. T.; Lee, G. H.
Heterocycles 1996, 43, 969–975.

1774 Journal of Natural Products, 2008, Vol. 71, No. 10
Notes
(12) Sung, S. H.; Kwon, S. H.; Cho, N. J.; Kim, Y. C. Phytother. Res.
1997, 11, 500–503.
(13) Hwang, B. Y.; Lee, J. H.; Nam, J. B.; Kim, H. S.; Hong, Y. S.; Lee,
J. J. J. Nat. Prod. 2002, 65, 616–617.
(14) Seo, C. S.; Lee, Y. K.; Kim, Y. J.; Jung, J. S.; Jahng, Y. D.; Chang,
H. W.; Song, D. K.; Son, J. K. Biol. Pharm. Bull. 2008, 31, 523–526.
(15) Hwang, B. Y.; Lee, J. H.; Nam, J. B.; Hong, Y. S.; Lee, J. J.
Phytochemstry 2003, 64, 765–771.
(16) Fonseca, S. F.; Barata, L. E. S.; Ruveda, E. A. Can. J. Chem. 1979,
441–443.
(17) Rimando, A. M.; Pezzuto, J. M.; Farnsworth, N. R.; Santisuk, T.;
Reutrakul, V.; Kawanishi, K. J. Nat. Prod. 1994, 57, 896–904.
(18) Rao, K. V.; Oruganty, R. S. J. Liq. Chromatogr. Relat. Technol. 1997,
20, 3121–3134.
(19) Tofern, B.; Jenett-Siems, K.; Siems, K.; Jakupovic, J.; Eich, E.
Phytochemistry 2000, 53, 119–128.
(24) Baraga, A. C. H.; Zacchino, S.; Badano, H.; Sierra, M. G.; Ruveda,
E. A. Phytochemistry 1984, 23, 2025–2028.
(25) Zacchino, S. A.; Badano, H. J. Nat. Prod. 1985, 48, 830–833.
(26) Zacchino, S. A.; Badano, H. J. Nat. Prod. 1988, 51, 1261–1264.
(27) Zacchino, S. A. J. Nat. Prod. 1994, 57, 446–448.
(28) Barata, L. E.; Baker, P. M.; Gottlieb, O. R.; Ruveda, E. A.
Phytochemistry 1978, 17, 783–786.
(29) Hattori, M.; Hada, S.; Kawata, Y.; Tezuka, Y.; Kikuchi, T.; Namba,
T. Chem. Pharm. Bull. 1987, 35, 3315–3322.
(30) Fernandes, A. M. A. P.; Barata, L. E. S.; Ferri, P. H. Phytochemistry
1994, 36, 533–534.
(31) Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 95, 512–519.
(32) Rieser, M. J.; Hui, Y. H.; Rupprecht, J. K.; Kozlowski, J. F.; Wood,
K. V.; Mclaughlin, J. L.; Hanson, P. R.; Zhuang, A.; Hoye, T. R.
J. Am. Chem. Soc. 1992, 144, 10203–10213.
(20) Kraft, C.; Jenett-Siems, K.; Ko¨hler, J.; Tofen-Reblin, B.; Siems, K.;
Bienzle, U.; Eich, E. Phytochemistry 2002, 60, 167–173.
(21) Yue, J. M.; Chen, Y. Z.; Hua, S. M.; Cheng, J. L.; Cui, Y. X.
Phytochemistry 1989, 28, 1774–1776.
(33) Rieser, M. J.; Fang, X. P.; erson, E.; Miesbauer, L. R.; Smith, D. L.;
Mclaughlin, J. L. HelV. Chim. Acta 1994, 76, 2433–2444.
(34) Urzua, A.; Freyer, A. J.; Shamma, M. Phytochemistry 1987, 26, 1509–
1511.
(22) Prasad, A. K.; Tyagi, O. D.; Wengel, J.; Boll, P. M.; Olsen, C. E.;
Bisht, K. S.; Singh, A.; Sarangi, A.; Kumar, R.; Jain, S. C.; Parmar,
V. S. Phytochemistry 1995, 39, 655–658.
(23) Sarkanen, K. V.; Wallis, A. F. A. J. Heterocycl. Chem. 1973, 10, 1025–
1027.
(35) Rubinstein, L. V.; Shoemaker, R. H.; Paul, K. D.; Simon, R. M.; Tosini,
S.; Skehan, P.; Scudiero, D. A.; Monks, A.; Boyd, M. R. J. Nat. Cancer
Inst. 1990, 82, 1113–1118.
NP8002723