Diarylheptanoids from the rhizomes of Zingiber officinale

Article abstract of DOI:10.1016/j.phytochem.2004.03.007

Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3- methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)- 7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3- methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4- hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7- (3,4-dihydroxy-5-methoxy-phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4- hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids, 14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.

Full text of DOI:10.1016/j.phytochem.2004.03.007

Phytochemistry 65 (2004) 1137–1143
www.elsevier.com/locate/phytochem
Diarylheptanoids from the rhizomes of Zingiber officinale
Jianping Ma, Xiaoling Jin, Li Yang, Zhong-Li Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
Received 11 December 2003; received in revised form 12 February 2004
Abstract
Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-
hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-
methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxy-
phenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one,
5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxy-
phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were
isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids,
14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.
# 2004 Elsevier Ltd. All rights reserved.
Keywords: Ginger; Zingiber officinale; Zingiberaceae; Diarylheptanoid
1. Introduction
hydroxy-3-methoxyphenyl)heptan-3-one
(2b),
5-
hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihy-
droxy-5-methoxyphenyl)heptan-3-one (2c) and 1,5-
epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-
(4-hydroxy-3-methoxyphenyl)heptane (3). Also iso-
lated and identified were 25 known compounds, i.e.,
four acyclic diarylheptanes (1d–g), two diarylhepta-
nones (2d and 2e), a cyclic diarylheptane (4), a di-
arylheptenone (5), a paradol (6), three gingerdiols (7a–
c), six gingerols (8a–f), a dehydrogingerdione (9), two
shogaols (10a and 10b), a phenylpropanoid (11), a
diterpene (12) and two steroids (13 and 14) (Fig. 1).
Compound 7a was reported previously as a synthetic
product from reduction of [6]-gingerol (Kikuzaki et al.,
1992), and this is the first time it has been isolated from
ginger and reported as a natural product. Compounds
2d and 11 have been identified by GC-MS, but no spec-
troscopic data were reported previously (Harvey, 1981;
Kraus et al., 1990).
Ginger, the rhizome of Zingiber officinale Roscoe
(Zingiberaceae), is one of the most popular spices and
has been frequently used in Chinese traditional medi-
cines both in fresh and dried forms (Huang et al., 1997).
Numerous chemical investigations of this plant material
have led to the isolation and identification of a large
number of biologically active compounds, such as gin-
gerols, gingerones and shogaols (Uehara et al., 1987;
Kikuzaki et al., 1991a,b; Endo et al., 1990; Kikuzaki et
al., 1992; Yu et al., 1998). We wish to report herein the
isolation and structural elucidation of seven previously
unknown diarylheptanoids from the ethanol extract of
the rhizomes of Z. officinale. These new compounds
are (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxy-
phenyl)heptane (1a), (3R,5S)-3-acetoxy-5-hydroxy-1,7-
bis(4-hydroxy-3-methoxyphenyl)heptane (1b), (3R,5S)-
3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-
hydroxy-3-methoxyphenyl)heptane (1c), (5S)-5-acetoxy-
1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one (2a), 5-
hydroxy - 1- (3,4 - dihydroxy - 5 - methoxyphenyl) - 7 - (4 -
2. Results and discussion
The petroleum ether and ethyl acetate fractions of the
ethanol extract of the rhizomes of Z. officinale were
separated by repeated column chromatography on silica
* Corresponding author. Tel.: +86-931-891-2500; fax: +86-931-
862-5657.
E-mail address: liuzl@lzu.edu.cn (Z.-L. Liu).
0031-9422/$ - see front matter # 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.phytochem.2004.03.007

1138
J. Ma et al. / Phytochemistry 65 (2004) 1137–1143
overlapped, two signals of the two compounds were
apparently distinguishable. These were the resonances
of C-3/C-5 (ꢁ 69.72 and 70.64 for 1a and 1d respectively)
and C-2/C-6 (ꢁ 36.66 and 35.91for 1a and 1d respec-
tively). Deacetylation of 1a and 1d with KOH/MeOH
gave the corresponding 3,5-dihydroxyl derivatives 1f
and 1g which were identified as (3S,5S)- and (3R,5S)-3,5-
dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptanes,
respectively, by comparing their 1H and 13C NMR
spectral data and optical rotations with those reported
in the literature (Kikuzaki et al., 1991a). Therefore,
compound 1a was assigned as (3S,5S)-3,5-diacetoxy-
1,7-bis(4-hydroxy-3-methoxyphenyl)heptane.
Compound 1b was obtained as a colorless oil, [ꢀ]D24
+6.0ꢀ (c 0.56, CHCl3). Its HR-ESI-MS spectrum
exhibited an [M+NH4]+ ion peak at m/z 436.2324,
corresponding to the molecular formula of C23H30O7
[calc. for [M+NH4]+: 436.2330]. The aromatic regions
1
in the H and 13C NMR spectra of 1b were identical to
that of 1a, suggesting that 1b possessed also two 4-
hydroxy-3-methoxyphenyl groups that was supported
by the characteristic base peak at m/z 137 in its EI-MS
spectrum (Uehara et al., 1987). The presence of one
acetyl group and the distinctive difference between sig-
nals of C-3 and C-5 (ꢁ 66.24 and 71.41 respectively)
suggested that 1b was a monoacetylated derivative of 1f
or 1g. Acetylation of 1b with acetic anhydride in pyri-
dine introduced three additional acetyl groups to the
molecule producing an optically inactive molecule
whose 1H NMR data were identical to those of 1h
reported in the literature (Kikuzaki et al., 1991a).
Therefore, compound 1b was assigned as (3R,5S)-3-
acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-
heptane.
Compound 1c was obtained as colorless oil, [ꢀ]2D4 0 (c
0.55, CHCl3). Its HR-ESI-MS spectrum exhibited an
[M+NH4]+ ion peak at m/z 424.2326 corresponding to
a molecular formula C22H30O7 (calc. for M+NH4:
Fig. 1. Constituents isolated from ginger.
1
424.2330). Its H and 13C NMR and IR spectra were
gel to afford seven new diarylheptanoids (1a, 1b, 1c, 2a,
2b, 2c and 3) along with 25 known compounds, 1d–g,
2d–e, 4–14 as shown in Fig. 1.
similar to those of the known compound (3S,5S)-3,5-
dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-
hydroxy-3-methoxyphenyl)heptane (1i) (Yamahara et
al., 1992). However, appreciable differences in the 13C
NMR chemical shifts were observed between both
molecules. That is, chemical shifts of C-1, C-4 and C-7
of 1c were upfield 0.6, 0.5 and 0.5 ppm, respectively,
while those of C-2/C-6 and C-3/C-5 were downfield 0.7
and 3.4 ppm, respectively, in comparison with those of
1i. These facts suggested that 1c is a stereoisomer of 1i.
Since 1i was optically active ([ꢀ]2D0 ꢁ24.0ꢀ, c 1.0, EtOH)
(Yamahara et al., 1992) while 1c was optically inactive,
and diarylheptanes isolated from rhizomes of Zingiber
officinale all possess S-configuration at the C-5 position
(Uehara et al., 1987; Kikuzaki et al., 1991a,b; Endo et
al., 1990; Kikuzaki et al., 1992; Yu et al., 1998), com-
pound 1c was assigned as (3R,5S)-dihydroxy-1-(4-
Compound 1a was obtained as a colorless oil, [ꢀ]D26
+7.0ꢀ (c 0.68, CHCl3). The HR-ESI-MS spectrum
exhibited an [M+NH4]+ ion peak at m/z 478.2431
corresponding to a molecular formula of C25H32O8
(calc. for M+NH4: 478.2435). The IR, UV and HR-
ESI-MS spectra of 1a were completely identical with
those of the known compound (3R,5S)-3,5-diacetoxy-1,7-
bis(4-hydroxy-3-methoxyphenyl)heptane (1d) (Kikuzaki
et al., 1991b) which was also obtained from the ethanol
extract of the rhizomes of Zingiber officinale. However,
unlike 1d (a meso compound) 1a was found to be opti-
cally active, suggesting that 1a was a stereoisomer of 1d.
Comparison of the 13C NMR spectrum of 1a with that
of 1d indicated that although most signals of both were

J. Ma et al. / Phytochemistry 65 (2004) 1137–1143
1139
hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxy-
phenyl)heptane.
heptan-3-one (5-acetyl-hexahydro-curcumin). Significant
HMBC correlations are shown in Fig. 2.
Compound 2a was obtained as a colorless oil, [ꢀ]D24
+3.0ꢀ (c 0.60, CHCl3). Its HR-ESI-MS spectrum
exhibited an [M+NH4]+ ion peak at m/z 434.2164
corresponding to a molecular formula of C23H28O7
(calc. for M+NH4: 434.2173). Its IR spectrum showed
characteristic absorptions for hydroxyl (3434 cmꢁ1),
carbonyl (1717 cmꢁ1) and aromatic (3015, 1606 and
Compounds 2b and 2c were obtained as a mixture in a
colorless oil and could not be further separated even by
HPLC. The HR-MALDI-MS spectrum exhibited a
unique M+Na ion peak at m/z 413.15708 correspond-
ing to the molecular formula C21H26O7 (calc. for
1
M+Na: 413.15762). The H and 13NMR spectra of the
mixture showed two sets of very similar signals for two
hexahydrocurcumin derivatives with almost the same
intensity. The EI-MS spectrum of the mixture showed a
characteristic base peak at m/z 137 ([CH2C6H3(O-
H)(OMe)]+) for the 4-hydroxy-3-methoxyphenyl moi-
ety in curcumin derivatives (Uehara et al., 1987) and a
strong peak at m/z 153 (61%) corresponding to a frag-
ment of ([CH2C6H2(OH)2(OMe)]+). These suggested
the presence of two phenyl rings with three and four
substituents (MeO, OH, and CH2, and MeO, OH, OH
and CH2, respectively). Careful analysis of their HMBC
and H,H-COSY spectra enabled the two compounds to
be distinguished as 5-hydroxy-1-(3,4-dihydroxy-5-meth-
oxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one
(2b) and 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-
1
1516 cmꢁ1) functionalities. The H NMR signals at ꢁ
6.81(dd, J=2.0, 8.0 Hz, 2H), 6.66 (d, J=2.0 Hz, 2H)
and 6.63 (d, J=8.0 Hz, 2H), as well as those at ꢁ 3.85 (s,
3H) and 3.87 (s, 3H), suggested the presence of two
1,3,4-trisubstituted phenyl groups bearing a methoxyl
group that was supported by the characteristic base
peak at m/z 137 ([CH2C6H3(OH)(OMe)]+) in its EI-MS
spectrum for the 4-hydroxy-3-methoxyphenyl moiety in
curcumin derivatives (Uehara et al., 1987). The 1H
NMR signal at ꢁ 2.00 (3H, s) and the 13C NMR signals
at ꢁ 21.04 and 170.41 revealed the presence of an acetyl
group that was supported by the fragment ion peak at
m/z 356 in the EI-MS spectrum from the deacetoxyla-
tion of the molecule. Comparison of its 1H and 13C
NMR spectral data with those of hexahydrocurcumin
(Uehara et al., 1987; Kikuzaki et al., 1991a,b) suggested
that 2a was an acetylated hexahydrocurcumin with an
acetyl group at C-5. This was confirmed by its HMBC
spectrum which showed a clear correlation between the
acetyl carbonyl carbon (ꢁ 170.41) and H-5 (ꢁ 5.26)
(Fig. 2). In order to determine the stereochemistry of
C-5, 2a was acetylated with acetic anhydride in pyridine
to yield 5,40,400-triacetoxy-hexahydrocurcumin (2f)
which was identical to the acetylation product of
hexahydrocurcumin obtained under the same experi-
mental conditions. Since the configuration of hexahy-
drocurcumin was known to be 5S (Uehara et al., 1987;
Kikuzaki et al., 1991a,b), compound 2a was assigned
as (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-
7-(3,4-dihydroxy-5-methoxyphenyl)heptan-3-one
(2c)
respectively. Their significant HMBC correlations are
shown in Fig. 2.
Compound 3 was obtained as a colorless oil, [ꢀ]D16
ꢁ24.0ꢀ (c 0.19, EtOH). The HR-MALDI-MS spectrum
exhibited an M+H ion peak at m/z 405.19078, corres-
ponding to the molecular formula C22H28O7 (calc. for
M+H: 405.19132). The 1H and 13C NMR spectral data
of 3 were very close to those of 1,5-epoxy-3-hydroxy-1-
(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-meth-
oxyphenyl)heptane (Kikuzaki et al., 1996) except that
the 3-hydroxyl group of the 1-phenyl moiety in the lat-
1
ter was methylated in 3 as evidenced from its H, 13C
and HMBC spectra. The coupling constants of H-3
(ꢁ 4.22, dddd, J=2.8, 3.0, 3.0 and 3.2 Hz) demonstrated
its equatorial orientation; hence the 3-hydroxyl group is
axial oriented. Therefore, 3 was assigned as 1,5-epoxy-3-
hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hy-
droxy-3-methoxyphenyl)heptane. The structure was
confirmed by the HMBC and H,H-COSY correlations
as shown in Fig. 3.
The structures of the known compounds were identi-
1
fied by comparing their H and 13C NMR, MS and IR
spectroscopic data and optical rotations with those
reported in the literature as follows: (3R,5S)-3,5-di-
Fig. 3. Significant HMBC (C!H) and H,H-COSY (–) correlations of 3.
Fig. 2. Significant HMBC (C!H) correlations of 2a, 2b and 2c.

1140
J. Ma et al. / Phytochemistry 65 (2004) 1137–1143
acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane (1d)
(Kikuzaki et al., 1991b), (3R,5S)-3,5-diacetoxy-1-(4-
hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxy-
phenyl)heptane (1e) (Kikuzaki et al., 1991b), (3S,5S)-3,5-
dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane
(1f) (Kikuzaki et al., 1991a), (3R,5S)-3,5-dihydroxy-1,7-
bis(4-hydroxy-3-methoxyphenyl)heptane (1g) (Kikuzaki
et al., 1991a), 5-hydroxy-1-(4-hydroxy-3-methoxyphen-
yl)-7-(3,4-dihydroxyphenyl)heptan-3-one (2d) (Harvey,
1981), hexahydrocurcumin (2e) (Uehara et al., 1987;
Kikuzaki et al., 1991b), 3-acetoxy-1,5-epoxy-1-(3,4-
dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxy-
phenyl)heptane (4) (Kikuzaki et al., 1996), 1,7-bis(4-
hydroxy-3-methoxyphenyl)hept-4-en-3-one (5) (Kiku-
zaki et al., 1991b), paradol (6) (Tackie et al., 1975),
(3S,5S)-[6]-gingerdiol (7a) (Kikuzaki et al., 1992), (3R,5S)-
[6]-gingerdiol (7b) (Kikuzaki et al., 1992), (3R,5S)-3,5-
diacetoxy-[6]-gingerdiol (7c) (Kikuzaki et al., 1992), [4]-
gingerol (8a) (Shoji et al., 1982; Denniff et al., 1980), [6]-
gingerol (8b) (Shoji et al., 1982; Denniff et al., 1980), 5-
acetoxy-[6]-gingerol (8c) (Shoji et al., 1982; Denniff et al.,
1980), 1-(3,4-dimethoxyphenyl)-5-hydroxy-decan-3-one
(8d) (Denniff et al., 1980), [8]-gingerol (8e) (Shoji et al.,
1982; Denniff et al., 1980), [10]-gingerol (8f) (Shoji et al.,
1982; Denniff et al., 1980), dehydrogingerdione (9)
(Kiuchi et al., 1982), [6]-shogaol (10a) (Connel and
Sutherland, 1969), [10]-shogaol (10b) (Connel and
Sutherland, 1969), 1-(3-methoxy-4-hydroxy-phenyl)-
propan-1,2-diol (11) (Kraus et al., 1990), galanolactone
(12) (Morita and Itokawa, 1988), b-sitosterol (13)
(Greca et al., 1990) and 6b-hydroxystigmast-4-en-3-one
(15) (Greca et al., 1990).
Comꢀpound 7a was obtained as colorless needles, mp
71–72 C. This compound had been synthesized from
reduction of [6]-gingerol (8b) (Kikuzaki et al., 1992), but
not previously been obtained from ginger or other
natural products.
Compounds 2d and 11 had been identified by GC–MS
(Harvey, 1981; Kraus et al., 1990), but no spectroscopic
data were reported previously. In this paper, their struc-
tures were assigned completely by spectroscopic methods.
The in vitro cytotoxicity against human promyelocy-
tic leukemia (HL-60) cells of most of the above men-
tioned compounds were tested using the [3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
(MTT) colorimetric assay (Price and McMillan, 1990)
with etoposide (VP-16) as a positive control. None of
them showed significant activity (data not shown).
internal standard. HR-ESI-MS and EI-MS data were
obtained on a Bruker APEX II FT-MS and a HP-5988
MS spectrometers respectively. The IR spectra were
taken on a Nicolet 170 SX IR spectrometer. Optical
rotations were measured on a Perkin-Elmer 341polari-
meter. Melting points were determined on a Yanagi-
moto melting point apparatus and uncorrected.
3.2. Plant material
Ginger, the rhizome of Zingiber officinale Roscoe was
collected in Hui county, Gansu province, China in
October 2001. A voucher specimen (No. G011001) was
preserved at the National Laboratory of Applied
Organic Chemistry, Lanzhou University, Lanzhou,
China and the plant sample was identified by Professor
Yong-Hong Zhang at the Department of Chemistry,
Lanzhou University.
3.3. Extraction and isolation
Slices of ginger were dried in the shade. The ground
ginger (800 g) was extracted repeatedly (5 times, 3 days
each time) with ethanol at room temperature. The eth-
anol extract (150 g) was suspended in water and succes-
sively extracted with petroleum ether, AcOEt and
n-BuOH. The petroleum ether and AcOEt extracts (35 g
and 30 g respectively) were subjected to column chro-
matography on silica gel (200–300 mesh) with a gradient
system of petroleum ether–acetone (20:1, 15:1, 10:1, 5:1,
3:1, 1:1 and 0:1). Repeated chromatography of each
fraction afforded 1a (4 mg), 1b (2 mg), 1c (2 mg), 1d (3
mg), 1e (2 mg), 1f (2 mg), 1g (3 mg), 2a (4 mg), 2b and
2c (2 mg), 2d (3 mg), 2e (3 mg), 3 (1mg), 4 (1mg), 5 (3
mg), 6 (50 mg), 7a (20 mg), 7b (15 mg), 7c (50 mg), 8a
(10 mg), 8b (80 mg), 8c (20 mg), 8d (6 mg), 8e (9 mg), 8f
(20 mg), 9 (8 mg), 10a (10 mg), 10b (6 mg), 11 (2 mg), 12
(10 mg), 13 (400 mg) and 14 (6 mg).
3.4. (3S,5S)-diacetoxy-1,7-bis(4-hydroxy-3-methoxy-
phenyl)heptane (1a)
Colorless oil. [ꢀ]2D6 +7.0ꢀ (c 0.68, CHCl3); [M+NH4]+
KBr
m/z 478.2431for C 25H36NO8 (Calc. 478.2435). IR ꢂ
max
cmꢁ1: 3438 (OH), 1731 (CO), 1607, 1516 (Ar). EI-MS
m/z (rel. int.): 460 (15) [M]+, 400 (4), 340 (3), 204 (5),
1
190 (17), 175 (7), 163 (13), 150 (12), 137 (100). For H
and 13C NMR spectral data, see Table 1.
3.5. 3R-acetoxy-5S-hydroxy-1,7-bis(4-hydroxy-3-
methoxyphenyl)heptane (1b)
3. Experimental
3.1. General
Colorless oil; [ꢀ]2D4 +6.0ꢀ (c 0.56, CHCl3). [M+NH4]+
KBr
m/z 436.2324 for C23H34NO7 (calc. 436.2330). IR ꢂ
max
1H, 13C, and 2D NMR spectra were recorded on a
Bruker AM 400 NMR spectrometer with TMS as
cmꢁ1: 3431 (OH), 1714 (CO), 1606, 1516 (Ar). EI-MS
m/z (rel. int.): 418 (8) [M]+, 358 (7), 190 (9), 163 (9), 150

Table 1
1H and 13C NMR chemical shifts for the new diarylheptanoids 1a, 1b, 1c, 2a, 2b, 2c and 3a
Posit.
1ab
1bb
1cb
2ab
2bc
2cc
3c
ꢁH
ꢁC
ꢁH
ꢁC
ꢁH
ꢁC
ꢁH
ꢁC
ꢁH
ꢁC
ꢁH
ꢁC
ꢁH
ꢁC
1a
1b
2a
2b
3
2.52 dt
2.53 dt
(14.0,6.8)
2.54 dt
(13.2,6.4)
1.80 ddd
(14.4,7.6, 4.0)
1.91 ddd
(14.4,8.8, 3.2)
5.11 m
2.63 dt
2.51 dt
(14.4,7.6)
dt
(15.6,7.8)
2.54 dt
(15.9,7.8)
(13.6,6.8)
2.70 dt
(13.6,6.4)
31.2
31.7
31.9
2.80 t (6.9)
t (6.3)
29.3
2.68 t (6.8)
2.76 m
32.12.60
32.3
4.73 d (9.6)
74.4
(13.2,7.6)
1.67 ddd
(2.8,2.8,2.8)
1.85 ddd
(11.2,2.8,2.4)
4.22 dddd
1.84 quart (7.2)
5.00 quint (6.0)
36.7
69.7
36.9
71.4
1.77 dt
(13.2,6.0)
3.89 m
40.12.69
72.5
45.2
45.8
2.76 m
45.9
41.7
63.6
206.9
210.2
210.2
(3.2,3.0,3.0, 2.8)
1.51 ddd
(13.2,2.8,2.0)
1.68 m
4a
4b
5
1.76 dt
(11.7,5.7)
1.92 dt
(14.1,6.9)
5.00 quint (6.0)
1.60 m
1.62 m
3.44 m
1.62 dt
(13.6,6.4)
dt
(13.2,6.0)
3.89 m
2.56 dd
(16.5,6.9)
2.68 dd
(16.8,6.3,)
5.26 quint (6.6)
38.6
69.7
4.737.11
66.2
43.2
72.4
47.4
70.0
2.57 dd (16.4,7.6)
4.02 quint (6.0)
50.8
67.6
2.57 dd
(16.4,7.6)
4.02
50.8
67.6
39.3
71.8
3.92 m
1.68 m
quint (6.0)
6a
6b
7a
7b
1.65 dt
(10.0,6.8)
1.74 dt
(9.2,5.2)
2.61 dt
(14.0,7.2)
2.73 ddd
(14.4,9.2, 5.6)
1.84 quart (7.2)
36.7
38.9
1.77 dt
(13.2,6.0)
2.63 dt
(13.6,6.8)
2.70 dt
(13.6,6.4)
4.08.611
dt
(12.9,5.4)
36.0
1.67 dt (15.2,7.2)
2.51 dt (14.4,7.6)
2.60 dt (13.2,7.6)
40.2
1.67 dt
(15.2,7.2)
4.07.711
dddd
(13.6,5.6,4.8,3.2)
39.2
2.52 dt
(15.6,7.8)
2.54 dt
(15.9,7.8)
31.2
31.8
31.4
2.56 dt
(16.5,6.9)
31.3
32.3
2.74 m
6.80 s
32.12.67
dt
(16.0,8.0)
31.9
10
20
30
40
50
60
133.2
110.9
146.3
143.7
114.2
120.8
133.1
111.0
146.4
143.9
114.2
120.9
132.9
105.0
147.0
132.9
147.0
105.0
132.8
111.1
146.4
143.9
114.3
120.8
134.0
109.6
148.2
133.1
148.9
104.7
133.6
112.9
146.0
134.5
115.6
121.4
135.4
104.5
148.5
135.8
148.5
104.5
6.67 d (1.8)
6.64 d (1.6)
6.42 s
6.66 s
6.34 s
6.68 s
6.81 d (8.1)
6.62 dd
(7.5,1.8)
6.81 d (8.0)
6.64 dd
(7.2,2.0)
6.82 d (7.8)
6.64 d (7.8)
6.71 d (8.0)
6.62 d (8.0)
6.42 s
6.70 s
6.34 s
6.80 s
6.68 s
6.79 s
100
200
300
400
500
600
133.2
110.9
146.3
143.7
114.2
120.8
134.1
111.1
146.4
143.7
114.4
120.9
133.6
111.0
146.5
143.8
114.3
120.9
133.0
111.0
146.4
144.0
114.3
120.8
133.6
113.0
146.0
134.5
115.6
121.5
134.0
109.7
148.2
133.1
148.9
104.6
134.6
113.0
148.5
145.4
115.6
121.6
6.67 d (1.8)
6.70 d (1.6)
6.66 s
6.34 s
6.34 s
6.81 d (8.1)
6.62 dd
(7.5,1.8)
2.00 s
6.82 d (8.8)
6.66 dd
(8.0,2.0)
2.06 s
6.84 d (7.6)
6.69 dd
(9.2,2.0)
6.82 d (7.8)
6.65 d (7.8)
6.71 d (8.0)
6.62 d (8.0)
6.71 d (8.4)
6.63 d (8.0)
3-OAc
21.1
170.7
21.0,
172.5
5-OAc
2.01 s
3.87 s
3.87 s
21.1
170.7
55.8
2.00 s
3.85 s
3.87 s
21.0
170.4
55.9
300-OMe
500-OMe
3 -OMe
500-OMe
3.87 s
3.87 s
55.9
55.9
3.87 s
3.87 s
3.87 s
56.3
56.3
55.9
3.79 s
3.76 s
56.2
56.4
3.82 s
3.82 s
3.78 s
56.7
56.7
56.2
3.77 s
3.80 s
56.4
56.2
55.8
55.9
a
Coupling constants (Hz) in parentheses.
Determined in CDCl3.
Determined in (CD3)2CO.
b
c

1142
J. Ma et al. / Phytochemistry 65 (2004) 1137–1143
1
(7), 137 (100). For H and 13C NMR spectral data see
Table 1.
(CD3)2CO, TMS): d 1.57 (2H, m, H-4), 1.70 (4H, m, H-2
and H-6), 2.55 (2H, dt, J=13.6 and 7.6 Hz, H-1a and
H-7a), 2.68 (2H, dt, J=13.6 and 8.0 Hz, H-1b and H-
7b), 3.80 (6H, s, 30-OMe and 300-OMe), 3.88 (2H, m, H-3
and H-5), 6.63 (2H, d, J=8.0 Hz, H-60 and H-600), 6.71
(2H, d, J=8.0 Hz, H-50 and H-500), 6.80 (2H, s, H-20 and
H-200). 13C NMR (100 MHz, (CD3)2CO, TMS): ꢁ 32.4
3.6. (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxy-
phenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (1c):
Colorless oil; [ꢀ]D24 0 (c 0.55, CHCl3); [M+NH4]+ m/z
424.2326 for C22H34NO7 (Calc. 424.2330). IR ꢂKmaBxr cmꢁ1
0
:
(C-1and C-7), 40.9 (C-2 and C-6), 44.7 (C-4), 56.2 (3 -
3412 (OH), 1726 (CO), 1612, 1517 (Ar). EI-MS m/z (rel.
int.): 406 (15) [M]+, 388 (3), 181 (12), 168 (86), 137 (83),
43 (100). For 1H and 13C NMR spectral data see Table 1.
OMe and 300-OMe), 68.3 (C-3 and C-5), 112.9 (C-20 and
C-200), 115.6 (C-50 and C-500), 121.5 (C-60 and C-600),
134.8 (C-10 and C-100), 145.3 (C-40 and C-400), 148.1 (C-30
and C-300). EIMS m/z (rel. int.): 376 (10) [M]+, 358 (7),
190 (6), 179 (5), 163 (6), 150 (8), 137 (100).
3.7. (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxy-
phenyl)heptan-3-one (2a)
3.11. Acetylation of 2a
Colorless oil; [ꢀ]2D4 +3.0o (c 0.60, CHCl3); [M+NH4]+
m/z 434.2164 for C23H32NO7 (Calc. 434.2173). IR ꢂ
KBr
max
Compound 2a (2 mg) was acetylated with Ac2O–pyr-
idine at room temperature to give 2f whose spectral data
were identical to those of the acetylation product of
hexahydrocurcumin (2e) under the same experimental
conditions. (5S)-5-acetoxy-1,7-bis(4-acetoxy-3- methoxy-
phenyl)-heptan-3-one (2f): Colorless oil. [ꢀ]2D5 ꢁ2.0ꢀ (c
0.18, CHCl3). [M+NH4]+ m/z 518.2387 for C27H32O9
cmꢁ1: 3434 (OH), 1717 (CO), 1606, 1516 (Ar). EI-MS
m/z (rel. int.): 416 (6) [M]+, 356 (6), 177 (3), 163 (4), 150
(9), 137 (100). For HMBC correlations see Fig. 2. For
1H and 13C NMR spectral data see Table 1.
3.8. 5-Hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-
(4-hydroxy-3-methoxyphenyl)heptan-3- one (2b) and
5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-
1
(calc. 518.2385). H NMR (400 MHz, CDCl3, TMS): ꢁ
1.90 (2H, dt, J=14.1 and 7.5 Hz, H-6), 1.99 (3H, s, 5-
OAc), 2.30 (6H, s, 40-OAc and 400-OAc), 2.59 (2H, dt,
J=11.7 and 5.7 Hz, H-7), 2.63 (1H, dd, J=13.5 and 7.5
Hz, H-4a), 2.73 (2H, t, J=6.9 Hz, H-2), 2.74 (1H, dd,
J=11.7 and 4.8 Hz, H-4b), 2.86 (2H, t, J=6.6 Hz, H-1),
3.80 (3H, s, 30-OMe), 3.82 (3H, s, 300-OMe), 5.28 (1H,
quint, J=6.3 Hz, H-5), 6.73 (2H, d, J=7.5 Hz, H-50 and
H-500), 6.78 (2H, s, H-20 and H-200), 6.92 (2H, d, J=6.6
Hz, H-60 and H-600). EI-MS m/z (rel. int.): 500 (2) M+,
458 (18), 398 (16), 356 (22), 137 (100).
(3,4-dihydroxy-5-methoxyphenyl)heptan-3-one (2c)
Colorless oil. [M+Na]+ m/z 413.15708 for C21H26O7Na
KBr
max
(calc. 413.15762). IR ꢂ
cmꢁ1: 3411 (OH), 1701 (CO),
1607, 1518 (Ar). EI-MS m/z (rel. int.): 390 (11) [M]+,
372 (3), 179 (8), 167 (11), 153 (61), 137 (100); For
HMBC correlations, see Fig. 2. For H and 13C NMR
spectral data see Table 1.
1
3.9. Acetylation of 1b
3.12. 5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-
(3,4-dihydroxyphenyl)heptan-3-one (2d)
Compound 1b (1mg) was acetylated with Ac O–pyr-
2
idine at room temperature to give 1h whose spectral
ꢀ
data were identical to those reported in the literature
Colorless needles; m.p. 163–164 C; [ꢀ]1D6 0 (c 0.74,
ꢀ
1
(Kikuzaki et al., 1991a). [ꢀ]2D5 0 (c 0.25, CHCl3). H
NMR (400 MHz, CDCl3, TMS): ꢁ 1.90–1.81 (6H, m, H-
2, H-4 and H-6), 2.02 (6H, s, 3-OAc, 5-OAc), 2.30 (6H,
s, 40-OAc and 400-OAc), 2.60 (4H, t, J=7.8 Hz, H-1and
H-7), 3.82 (6H, s, 30-OMe and 300-OMe), 5.03 (2H, m,
H-3 and H-5), 6.74 (2H, d, J=7.5 Hz, H-50 and H-500),
6.78 (2H, s, H-20 and H-200), 6.93 (2H, dd, J=8.1and 1.8
Hz, H-60 and H-600). EIMS m/z (rel. int.): 544 (0.3)
[M]+, 502 (6), 442 (6), 400 (7), 340 (7), 190 (15), 163 (13),
150 (9), 137 (87), 43 (100).
EtOH). [M+NH4]+ m/z 378.1923 for C20H24O6NH4
KBr
max
(calc. 378.1911). IR ꢂ
cmꢁ1: 3392 (OH), 1703 (CO),
1606, 1518 (Ar). 1H NMR (400 MHz, (CD3)2CO,TMS):
ꢁ 1.66 (2H, dt, J=14.4 and 7.2 Hz, H-6), 2.48 (1H, dt,
J=13.6 and 8.1 Hz, H-7a), 2.56 (2H, d, J=6.0 Hz, H-
4), 2.61(1H, dt, J=14.4 and 8.0 Hz, H-7b), 2.74 (2H, t,
J=6.8 Hz, H-1), 2.76 (2H, t, J=6.8 Hz, H-2), 3.79 (3H,
s, 30-OMe), 4.01(1H, quint, J=6.0 Hz, H-5), 6.50 (1H,
d, J=8.8 Hz, H-600), 6.62 (1H, d, J=8.4 Hz, H-60), 6.67
(1H, s, H-200), 6.70 (2H, d, J=7.6 Hz, H-50 and H-500),
6.80 (1H, s, H-20). 13C NMR (100 MHz, (CD3)2CO,
TMS): d 29.4 (C-1), 31.8 (C-7), 40.2 (C-6), 45.9 (C-2),
50.8 (C-4), 56.2 (30-OMe), 67.6 (C-5), 112.9 (C-20), 115.6
(C-500), 115.8 (C-50), 116.2 (C-200), 120.3 (C-600), 121.4
(C-60), 133.6 (C-10), 134.7 (C-100), 143.7 (C-300), 145.5
(C-40), 145.6 (C-400), 148.2 (C-30), 210.3 (C-3). EI-MS m/
z (rel. int.): 360 (6) [M]+, 248 (8), 150 (16), 137 (100).
3.10. Hydrolysis of 1a
Compound 1a (2 mg) was hydrolyzed with KOH/
MeOH to give 1f whose spectral data were identical to
those reported in the literature (Kikuzaki et al., 1991a).
[ꢀ]2D7 ꢁ7.0ꢀ (c 0.18, CHCl3). 1H NMR (400 MHz,

J. Ma et al. / Phytochemistry 65 (2004) 1137–1143
1143
3.13. 1,5-Epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimeth-
oxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (3)
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Acknowledgements
We thank the National Natural Science Foundation
of China (Grant Nos. 20172025 and 20332020) for
financial support.
Yu, Z., Wu, H., Ding, J., 1998. The volatile chemical components of
fresh Zingiber officinale. Acta Botanica Yunnanica 20, 113–118.