Four new lignan glycosides from osmanthus fragrans lour. var. aurantiacus makino

Article abstract of DOI:10.1002/hlca.201000074

Four new tetrahydrofuranoid lignan glycosides, (7S,8R,7′R,8′S)- 4,9,4′,7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxylignan 9-O-β-D-glucopyranoside (2), (7R,8S,7′S,8′R)-4,9,4′, 7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxylignan 9-O-β-D-glucopyranoside (3), (7R,8S,7′R,8′S)-4,9,4′, 9′-tetrahydroxy-3,3′-dimethoxy-7,7′-epoxylignan 9-O-β-D-glucopyranoside (4), and rel-(7R,8S,7′S,8′R)-4,9, 4′,9′-tetrahydroxy-3,3′-dimethoxy-7,7′-epoxylignan 9-O-β-D-glucopyranoside (5), and ten known lignan glycosides, 1 and 6-14, were isolated from the leaves of Osmanthus fragrans Lour. var. aurantiacus Makino. Their structures were established on the basis of spectral and chemical studies. Copyright 2010 Verlag Helvetica Chimica Acta AG, Zuerich, Switzerland.

Full text of DOI:10.1002/hlca.201000074

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Four New Lignan Glycosides from Osmanthus fragrans Lour. var.
aurantiacus Makino
by Koichi Machida, Megumi Yamauchi, Eriko Kurashina, and Masao Kikuchi*
Department of Molecular Structural Analysis, Tohoku Pharmaceutical University, 4-4-1 Komatsushima,
Aoba-ku, Sendai, Miyagi 981-8558, Japan (phone: þ 81-22-2344181; fax: þ 81-22-2752013;
e-mail: mkikuchi@tohoku-pharm.ac.jp)
Four new tetrahydrofuranoid lignan glycosides, (7S,8R,7’R,8’S)-4,9,4’,7’-tetrahydroxy-3,3’-dimeth-
oxy-7,9’-epoxylignan 9-O-b-d-glucopyranoside (2), (7R,8S,7’S,8’R)-4,9,4’,7’-tetrahydroxy-3,3’-dimeth-
oxy-7,9’-epoxylignan 9-O-b-d-glucopyranoside (3), (7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dimeth-
oxy-7,7’-epoxylignan 9-O-b-d-glucopyranoside (4), and rel-(7R,8S,7’S,8’R)-4,9,4’,9’-tetrahydroxy-3,3’-
dimethoxy-7,7’-epoxylignan 9-O-b-d-glucopyranoside (5), and ten known lignan glycosides, 1 and 6 – 14,
were isolated from the leaves of Osmanthus fragrans Lour. var. aurantiacus Makino. Their structures
were established on the basis of spectral and chemical studies.
Introduction. – Osmanthus fragrans Lour. var. aurantiacus Makino belongs to the
Oleaceae family. This family is a rich source of iridoid, secoiridoid, phenylpropanoid,
and lignan glycosides [1]. As part of our continuing studies on the constituents of
oleaceous plants, we previously reported the isolation and identification of three new
phenylpropanoids, two new secoiridoid glycosides, along with 24 known compounds
from the leaves of this plant [2 – 4]. The flower of this plant has been used in China as a
herbal drug against toothache and as gargle [5]. In the course of further studies on the
constituents of this plant, four new tetrahydrofuranoid lignan glycosides
(7S,8R,7’R,8’S)-4,9,4’,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 9-O-b-d-gluco-
pyranoside1) (2), (7R,8S,7’S,8’R)-4,9,4’,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxyli-
gnan 9-O-b-d-glucopyranoside1) (3), (7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dime-
thoxy-7,7’-epoxylignan 9-O-b-d-glucopyranoside1) (4), and rel-(7R,8S,7’S,8’R)-4,9,4’,9’-
tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan 9-O-b-d-glucopyranoside1) (5), and ten
known lignan glycosides, 1 and 6 – 14, have been isolated. This article deals with the
structural elucidation and identification of these compounds.
Results and Discussion. – The MeOH extract of the fresh leaves of O. fragrans
Lour. var. aurantiacus Makino was partitioned with CHCl3, AcOEt, BuOH, and H2O.
The BuOH-soluble fraction was separated by a combination of chromatographic
procedures to afford four new tetrahydrofuranoid-lignan glycosides, 2 – 5, and ten
known lignan glycosides, 1 and 6 – 142). The known compounds 1 and 6 – 14 were
identified as tanegoside A (1) [6], (þ)-lariciresinol 4-O-b-d-glucopyranoside (6) [7],
1
)
)
Trivial atom numbering; for systematic names, see Exper. Part.
For formulae, see corresponding references.
2
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 93 (2010)
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(þ)-lariciresinol 4’-O-b-d-glucopyranoside (7) [7], (ꢀ)-olivil 4-O-b-d-glucopyranoside
(8) [8], (ꢀ)-olivil 4’-O-b-d-glucopyranoside (9) [8][9], (þ)-8-hydroxypinoresinol 8-O-
b-d-glucopyranoside (10) [10], (7S,8R)-dehydrodiconiferyl alcohol 4-O-b-d-glucopyr-
anoside (11) [11], (7R,8S)-dehydrodiconiferyl alcohol 9-O-b-d-glucopyranoside (12)
[12], (þ)-isolariciresinol 6-O-b-d-glucopyranoside (13) [13][14], and (þ)-isolaricire-
sinol 9’-O-b-d-glucopyranoside (14) [14][15] by comparison of their spectroscopic data
with those described in the literature. This is the first time of the identification of 1 and
6 – 14 in this plant.
Compound 2 was obtained as an optically active hygroscopic amorphous powder.
The molecular formula of 2, C26H34O12, was deduced from HR-FAB-MS (m/z 561.1944
([M þ Na]þ)). In the 1H-NMR spectrum of 2 (Table 1), two sets of 1,3,4-trisubstituted
benzene ring signals at d(H) 7.00 (d, J ¼ 2.0, HꢀC(2’)), 6.83 (dd, J ¼ 8.1, 2.0, HꢀC(6’)),
6.77 (d, J ¼ 8.1, HꢀC(5’)), 6.91 (d, J ¼ 2.0, HꢀC(2)), 6.82 (dd, J ¼ 8.1, 2.0, HꢀC(6)),
and 6.75 (d, J ¼ 8.1, HꢀC(5)), two MeO signals at d(H) 3.84 (s, MeOꢀC(3)) and 3.87
(s, MeOꢀC(3’)), and an anomeric H-atom signal at d(H) 4.26 (d, J ¼ 7.6, HꢀC(1’’))
1
were observed. Furthermore, the H-NMR spectrum exhibited signals attributable to

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Helvetica Chimica Acta – Vol. 93 (2010)
two O-bearing CH groups at d(H) 4.65 (d, J ¼ 8.3, HꢀC(7)) and 4.54 (d, J ¼ 8.5,
HꢀC(7’)), two O-bearing CH2 groups at d(H) 3.98 (dd, J ¼ 10.0, 5.1, HBꢀC(9)), 3.65
(dd, J ¼ 10.0, 5.3, HAꢀC(9)), 3.76 (dd, J ¼ 9.3, 5.6, HBꢀC(9’)), and 3.70 (dd, J ¼ 9.3, 6.3,
HAꢀC(9’)), and two aliphatic CH groups at d(H) 2.82 (br. ddd, J ¼ 8.3, 6.3, 5.6,
HꢀC(8’)) and 2.38 (br. dd, J ¼ 8.3, 5.3, 5.1, HꢀC(8)). Acid hydrolysis of 2 yielded d-
glucose, which was identified on the basis of retention time (HPLC) and optical
rotation. The 1H,1H-COSY experiment of 2 in combination with the HMQC spectrum
1
revealed the partial structures shown by the bold lines in Fig. 1. The H-NMR data
(Table 1) of 2 were similar to those of 1 (tanegoside A ¼ (7S,8R,7’S,8’S)-4,9,4’,7’-
tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 7’-O-b-d-glucopyranoside ¼ (S)-(4-hy-
droxy-3-methoxyphenyl)-[(3S,4R,5S)-tetrahydro-5-(4-hydroxy-3-methoxyphenyl)-4-
(hydroxymethyl)-3-furanyl]methyl O-b-d-glucopyranoside) [6], except for the chem-
ical shifts due to HꢀC(8), CH2(9), HꢀC(7’), and HꢀC(8’). The 13C-NMR spectra
(Table 1) of 2 were also similar to those of 1, except for significant upfield shifts of C(8)
(d(C) 50.5, ꢀ 2.80 ppm) and C(7’) (d(C) 77.5, ꢀ 3.80 ppm), and downfield shifts of
Table 1. 1H- and 13C-NMR Data (400 and 100 MHz, resp.; in CD3OD) of 1 and 21). d in ppm, J in Hz.
1
2
d(H)
d(C)
d(H)
d(C)
C(1)
–
134.3
111.4
149.3
147.3
116.0
120.7
85.4
–
134.2
111.2
149.1
147.2
115.9
120.7
85.5
HꢀC(2)
6.95 (d, J ¼ 2.0)
6.91 (d, J ¼ 2.0)
C(3)
–
–
–
–
C(4)
HꢀC(5)
HꢀC(6)
HꢀC(7)
HꢀC(8)
CH2(9)
6.76 (d, J ¼ 8.1)
6.84 (dd, J ¼ 8.1, 2.0)
4.59 (d, J ¼ 7.8)
1.97 (br. ddd, J ¼ 10.2, 7.8, 5.6)
3.17 (dd, J ¼ 11.2, 5.6),
3.26 (overlapped)
3.86 (s)
6.75 (d, J ¼ 8.1)
6.82 (dd, J ¼ 8.1, 2.0)
4.65 (d, J ¼ 8.3)
2.38 (br. ddd, J ¼ 8.3, 5.3, 5.1)
3.65 (dd, J ¼ 10.0, 5.3),
3.98 (dd, J ¼ 10.0, 5.1)
3.84 (s)
53.3
62.1
50.5
70.5
MeOꢀC(3)
C(1’)
56.6
132.0
112.3
149.0
147.6
115.8
122.2
81.3
56.5
136.4
111.6
149.0
147.3
115.9
120.9
77.5
–
–
HꢀC(2’)
7.02 (d, J ¼ 1.7)
7.00 (d, J ¼ 2.0)
C(3’)
–
–
–
–
C(4’)
HꢀC(5’)
HꢀC(6’)
HꢀC(7’)
HꢀC(8’)
CH2(9’)
6.73 (d, J ¼ 8.1)
6.77 (dd, J ¼ 8.1, 1.7)
4.81 (d, J ¼ 8.5)
2.62 (br. ddd, J ¼ 8.5, 4.6, 4.1)
3.88 (dd, J ¼ 9.0, 4.6),
4.31 (dd, J ¼ 9.0, 4.1)
3.83 (s)
4.06 (d, J ¼ 7.6)
3.26 (overlapped)
3.26 (overlapped)
3.26 (overlapped)
3.10 (ddd, J¼ 8.8, 6.3, 2.2)
3.66 (dd, J ¼ 11.9, 6.3),
3.87 (dd, J ¼ 11.9, 2.2)
6.77 (d, J ¼ 8.1)
6.83 (dd, J ¼ 8.1, 2.0)
4.54 (d, J ¼ 8.5)
2.82 (br. ddd, J ¼ 8.3, 6.3, 5.6)
3.70 (dd, J ¼ 9.3, 6.3),
3.76 (dd, J ¼ 9.3, 5.6)
3.87 (s)
4.26 (d, J ¼ 7.6)
3.30 (overlapped)
3.30 (overlapped)
3.30 (overlapped)
3.30 (overlapped)
3.70 (overlapped),
3.86 (overlapped)
49.8
71.6
53.0
71.0
MeOꢀC(3’)
HꢀC(1’’)
HꢀC(2’’)
HꢀC(3’’)
HꢀC(4’’)
HꢀC(5’’)
CH2(6’’)
56.4
100.4
75.2
78.0
72.0
78.0
63.0
56.4
104.8
75.3
78.3
71.6
78.1
62.8

Helvetica Chimica Acta – Vol. 93 (2010)
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Fig. 1. 1H,1H-COSY Correlations (—) and key HMBCs
(H ! C) of 2 and 3
C(9) (d(C) 70.5, þ 8.4 ppm) and C(8’) (d(C) 53.0, þ 3.2 ppm). These findings
suggested that b-d-glucopyranosyloxy group in 2 is attached to C(9) of 4,9,4’,7’-
tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan, and not to C(7’). Detailed analyses of
1
1
the H- and 13C-NMR (Table 1) signals of 2 were undertaken with the aid of H,1H-
COSY, HMQC, and DEPT experiments, and the constitutional structure of 2 was
identified as 4,4’,9,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 9-O-b-d-glucopyr-
anoside by the HMBC experiment (Fig. 1). In the NOESY spectrum (Fig. 2), HꢀC(8)
showed NOE correlations with 2 HꢀC(2,6) and HꢀC(7’), whereas HꢀC(8’) showed
NOE correlations with HꢀC(7), HAꢀC(9), and 2 HꢀC(2’,6’). These NOE correla-
tions of 2 were very similar to those of 1; however, no NOE correlation between
HꢀC(8) and 2 HꢀC(2’,6’) was observed. The coupling constant of HꢀC(7’) (J ¼
8.5 Hz) in 2 revealed an antiperiplanar orientation of HꢀC(7’) and HꢀC(8’).
Enzymatic hydrolysis of each 1 and 2 afforded the aglycones 1a and 2a, and the
NOE correlations of 1a and 2a were the same as those of 1 and 2, respectively. The
1
comparison of the H-NMR chemical shifts of 1a and 2a reveal shift changes for
HꢀC(8), CH2(9), and CH2(9’). The signals of HꢀC(8) (d(H) 2.29), CH2(9) (d(H)
3.63, 3.74), and CH2(9’) (d(H) 3.58, 3.65) of 2a were shifted downfield (þ0.31 ppm),
downfield (þ0.23, þ 0.34 ppm), and upfield (þ0.54, þ 0.42 ppm) with respect to those
of 1a, respectively. These shifts are attributed to the anisotropic effect of the aromatic
group at C(7’) in (Fig. 3), suggesting that the aglycone parts of 1 and 2 are epimers at
C(7’). On the other hand, the CD spectrum of 2 showed two positive Cotton effects
(De þ 15.2 (206 nm), þ 3.5 (235 nm)) similar to those of 1 (De þ 17.6 (210 nm), þ 4.6
(237 nm)) and of analogous compound (tinosposide B ¼ (7S,8R,7’S,8’S)-4,9,7’-trihy-
droxy-3,3’,4’-trimethoxy-7,9’-epoxylignan 4-O-b-d-glucopyranoside) [16] indicating
that C(7), C(8), and C(8’) in 2 have (S)-, (R)-, and (S)-configurations, respectively.
Therefore, the remaining stereogenic center at C(7’) of 2 is (R)-configurated.
Consequently, the structure of 2 was determined to be (7S,8R,7’R,8’S)-4,9,4’,7’-
tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 9-O-b-d-glucopyranoside.
Compound 3 was obtained as an optically active hygroscopic amorphous powder.
The molecular formula of 3, C26H34O12, was determined by HR-FAB-MS and was the
same as that of 2. Acid hydrolysis of 2 yielded d-glucose, which was identified as
described above. Its 1H- and 13C-NMR spectra (Table 2) were very similar to those of 2.
The 1H,1H-COSY and HMBC (Fig. 1) experiments of 3 led to the same planar

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Helvetica Chimica Acta – Vol. 93 (2010)
Fig. 2. NOESY Correlations (H $ H) of 1, 2, and 3 (R ¼ b-d-glucopyranosyl)
Fig. 3. Magnetic anisotropy effects of the aromatic group at C(7’) of 1a, 2a, and 3a
structure as the one of 2. The NOE correlations of 3 (Fig. 2) were also the same as
those of 2. On the other hand, the CD curves of 2 and 3 were symmetrical opposites (2:
De þ 15.2 (206 nm), þ 3.5 (235 nm); 3: De ꢀ 12.9 (205 nm), ꢀ 2.5 (234 nm)).

Helvetica Chimica Acta – Vol. 93 (2010)
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Enzymatic hydrolysis of 3 afforded an aglycone, 3a, and the spectral data of 3a were in
agreement with those of 2a, except for the signs of the optical rotations (2a: [a]D ¼
þ35.1; 3a: [a]D ¼ ꢀ35.7) and the CD curves (2a: De þ 20.0 (206 nm), þ 5.8
(234 nm); 3a: De ꢀ 20.3 (205 nm), ꢀ 5.2 (235 nm)). Therefore, the aglycone parts of
2 and 3 were deduced to be enantiomers. Consequently, the structure of 3 was
determined to be (7R,8S,7’S,8’R)-4,9,4’,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxyli-
gnan 9-O-b-d-glucopyranoside.
Table 2. 1H- and 13C-NMR Data (400 and 100 MHz, resp.; in CD3OD) of 31). d in ppm, J in Hz.
d(H)
d(C)
HꢀC(1)
HꢀC(2)
C(3)
–
134.3
111.3
149.1
147.3
115.9
120.6
85.7
51.0
70.9
56.5
136.4
111.6
149.0
147.2
115.9
121.0
77.7
53.0
71.1
56.4
104.8
75.2
6.93 (d, J ¼ 2.0)
–
–
C(4)
HꢀC(5)
HꢀC(6)
HꢀC(7)
HꢀC(8)
CH2(9)
6.75 (d, J ¼ 8.1)
6.81 (dd, J ¼ 8.1, 2.0)
4.70 (d, J ¼ 7.8)
2.41 (br. ddd, J ¼ 8.5, 7.8, 5.1)
3.61 (dd, J ¼ 9.8, 5.1), 4.10 (dd, J ¼ 9.8, 5.4)
3.85 (s)
MeOꢀC(3)
C(1’)
–
HꢀC(2’)
C(3’)
C(4’)
6.99 (d, J ¼ 1.8)
–
–
HꢀC(5’)
HꢀC(6’)
HꢀC(7’)
HꢀC(8’)
CH2(9’)
MeOꢀ(3’)
HꢀC(1’’)
HꢀC(2’’)
HꢀC(3’’)
HꢀC(4’’)
HꢀC(5’’)
CH2(6’’)
6.77 (d, J ¼ 8.3)
6.83 (dd, J ¼ 8.3, 1.8)
4.51 (d, J ¼ 8.8)
2.68 – 2.71 (m)
3.66 (overlapped), 3.74 (dd, J ¼ 9.1, 5.1)
3.87 (s)
4.29 (d, J ¼ 7.8)
3.22 (dd, J ¼ 9.0, 7.8)
3.30 (overlapped)
3.30 (overlapped)
3.30 (overlapped)
3.73 (overlapped), 3.86 (overlapped)
78.2
71.7
78.1
62.8
Compound 4 was obtained as an optically active hygroscopic amorphous powder.
The molecular formula of 4, C26H34O12, was deduced from HR-FAB-MS. In the
1H-NMR spectrum of 4 (Table 3), two sets of 1,3,4-trisubstituted benzene ring signals
at d(H) 7.04 (d, J ¼ 2.0, HꢀC(2)), 7.02 (d, J ¼ 2.0, HꢀC(2’)), 6.91 (dd, J ¼ 8.1, 2.0,
HꢀC(6)), 6.89 (dd, J ¼ 8.1, 2.0, HꢀC(6’)), 6.79 (d, J ¼ 8.1, HꢀC(5)), and 6.78 (d, J ¼
8.1, HꢀC(5’)), two O-bearing CH group signals at d(H) 4.99 (d, J ¼ 9.0, HꢀC(7)), 4.98
(d, J ¼ 9.0, HꢀC(7’)), an anomeric H-atom signal at d(H) 4.24 (d, J ¼ 7.8, HꢀC(1’’)),
two O-bearing CH2 group signals at d(H) 4.03 (dd, J ¼ 10.0, 4.1, HBꢀC(9)), 3.78 (dd,
J ¼ 11.5, 4.1, HBꢀC(9’)), 3.71 (dd, J ¼ 10.0, 4.1, HAꢀC(9)), and 3.61 (dd, J ¼ 11.5, 4.3,
HAꢀC(9’)), two MeO signals at d(H) 3.88 (s, MeOꢀC(3), MeOꢀC(3’)), and two CH
group signals at d(H) 2.51 (br. ddd, J ¼ 9.0, 4.3, 4.1, HꢀC(8)) and 2.39 (br. ddd, J ¼ 9.0,

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Table 3. 1H- and 13C-NMR Data (400 and 100 MHz, resp.; in CD3OD) of 4 and 51). d in ppm, J in Hz.
4
5
d(H)
d(C)
d(H)
d(C)
C(1)
–
135.0
111.4
149.1
147.4
116.1
120.6
84.4
–
134.8
111.5
149.1
147.4
116.1
120.6
84.2
HꢀC(2)
7.04 (d, J ¼ 2.0)
7.04 (d, J ¼ 2.0)
C(3)
–
–
–
–
C(4)
HꢀC(5)
HꢀC(6)
HꢀC(7)
HꢀC(8)
CH2(9)
6.79 (d, J ¼ 8.1)
6.91 (dd, J ¼ 8.1, 2.0)
4.99 (d, J ¼ 9.0)
2.51 (br. ddd, J ¼ 9.0, 4.3, 4.1)
3.71 (dd, J ¼ 10.0, 4.3),
4.03 (dd, J ¼ 10.0, 4.1)
3.88 (s)
6.79 (d, J ¼ 8.1)
6.91 (dd, J ¼ 8.1, 2.0)
4.83 (d, J ¼ 6.7)
2.66 – 2.73 (m)
3.68 (overlapped),
4.24 (dd, J ¼ 10.0, 7.6)
3.85 (s)
51.9
70.0
50.2
68.4
MeOꢀC(3)
C(1’)
56.5
134.9
111.3
149.1
147.4
116.0
120.6
84.3
56.5
134.7
111.5
149.1
147.3
116.1
120.4
84.1
–
–
HꢀC(2’)
7.02 (d, J ¼ 2.0)
7.02 (d, J ¼ 1.7)
C(3’)
–
–
–
–
C(4’)
HꢀC(5’)
HꢀC(6’)
HꢀC(7’)
HꢀC(8’)
CH2(9’)
6.78 (d, J ¼ 8.1)
6.89 (dd, J ¼ 8.1, 2.0)
4.98 (d, J ¼ 9.0)
2.39 (br. ddd, J ¼ 9.0, 4.3, 4.1)
3.61 (dd, J ¼ 11.5, 4.3),
3.78 (dd, J ¼ 11.5, 4.1)
3.88 (s)
4.24 (d, J ¼ 7.8)
3.18 (dd, J ¼ 9.5, 7.8)
3.32 (overlapped)
3.32 (overlapped)
3.32 (overlapped)
3.66 (dd, J ¼ 12.0, 5.3),
3.86 (dd, J ¼ 12.0, 1.7)
6.79 (d, J ¼ 8.1)
6.93 (dd, J ¼ 8.1, 1.7)
4.81 (d, J ¼ 7.8)
2.51 – 2.58 (m)
3.68 (overlapped),
3.86 (overlapped)
3.84 (s)
4.29 (d, J ¼ 7.8)
3.19 (dd, J ¼ 9.4, 7.8)
3.32 (overlapped)
3.32 (overlapped)
3.32 (overlapped)
3.66 (overlapped),
3.85 (overlapped)
55.1
61.2
52.8
60.6
MeOꢀC(3’)
HꢀC(1’’)
HꢀC(2’’)
HꢀC(3’’)
HꢀC(4’’)
HꢀC(5’’)
CH2(6’’)
56.5
104.7
75.2
78.2
71.6
56.4
104.4
75.2
78.3
71.7
78.1
62.8
78.2
62.9
4.3, 4.1, HꢀC(8’)) were observed. The 13C-NMR spectrum of 4 (Table 3) was similar to
that of 3, except for the chemical shifts of C(7’) (d(C) 84.3, þ 6.6 ppm) and C(9’) (d(C)
61.2, ꢀ 9.9 ppm). These data indicated a 2,5-diaryl-tetrahydofuranoid type of neo-
lignan glycoside [17]. The complete assignments of the 1H- and 13C-NMR signals of 4
1
were confirmed by the H,1H-COSY, HMQC, HMBC (Fig. 4), and NOESY (Fig. 5)
experiments. On enzymatic hydrolysis, 4 gave an aglycone, 4a, and d-glucose, which was
identified as described above. Compound 4a was identified as (þ)-neoolivil
(¼(7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan) by the com-
1
parison of its optical rotation value ([a]D ¼ þ44.8), H-NMR spectrum, and EI-MS
data [18]. Furthermore, the CD spectrum of 4 (De þ 15.0 (208 nm), þ 7.8 (238 nm))
showed two positive Cotton effects similar to those of an analogous compound
((7R,8S,7’R,8’S)-(þ)-neoolivil-4-O-b-d-glucopyranoside; De þ 11.8 (211 nm), þ 6.7
(236 nm)) [19], indicating (R)-configurations at C(7) and C(7’). From the above data,
the structure of 4 was determined to be (7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-
dimethoxy-7,7’-epoxylignan 9-O-b-d-glucopyranoside.

Helvetica Chimica Acta – Vol. 93 (2010)
2171
Fig. 4. 1H,1H-COSY Correlations (—) and key HMBCs
(H ! C) of 4 and 5
Fig. 5. NOESY Correlations (H $ H) of 4
(R ¼ b-d-glucopyranosyl)
This structure had already been assigned to a compound previously isolated from
the bark of O. asiaticus by one of the authors (M. K.) [20]. However, the NMR
chemical shifts of 4 and those of the compound previously isolated are not identical.
After re-examining the previous spectral data, we found that the structure previously
designated as (7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan 9-
O-b-d-glucopyranoside from O. asiaticus should be revised to 1.
Compound 5 was obtained as an optically active hygroscopic amorphous powder.
The molecular formula of 5, C26H34O12, was deduced from HR-FAB-MS. The 1H- and
13C-NMR (Table 3) spectral data of 5 closely resembled those of 4, except for the
1
chemical shifts due to C(7), C(8), C(9), C(7’), C(8’), and C(9’) positions. The H,1H-
COSYand HMBC experiments (Fig. 4) of 5 led to the same planar structure as the one
of 4. On the other hand, the NOE correlations (2 HꢀC(2,6)/HꢀC(8), 2 HꢀC(2’,6’)/
HꢀC(8’), HꢀC(7)/CH2(9), HꢀC(7’)/CH2(9’), and HꢀC(8)/HꢀC(8’)) of 5 (Fig. 6)
indicated that the relative configurations between C(7) and C(8), and C(7’) and C(8’)
Fig. 6. NOESY Correlations (H $ H) of 5 (R ¼ b-d-
glucopyranosyl)

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Helvetica Chimica Acta – Vol. 93 (2010)
were established as trans, and between HꢀC(8) and HꢀC(8’) as cis. From the above
data, the aglycone of 5 has a symmetrical structure and a meso-configuration.
Enzymatic hydrolysis of 5 afforded an aglycone, 5a. The symmetrical structure and a
meso-configuration of the aglycone of 5 was also confirmed by the optical rotation
([a]D ¼ꢁ 0), CD data (no Cotton effect), and 1H-NMR signals (a set of signals for two
phenylpropanoid units) of 5a [21]. The position of the b-d-glucopyranosyl unit could
not be determined (at C(9) or C(9’)). Consequently, the structure of 5 was determined
to be rel-(7R,8S,7’S,8’R)-4,9,4’,9’-tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan 9-O-b-
d-glucopyranoside.
We thank Mrs. S. Sato and T. Matsuki of Tohoku Pharmaceutical University for NMR and MS
measurements.
Experimental Part
General. Column chromatography (CC): silica gel (SiO2; 230 – 400 mesh; Merck) and Sephadex LH-
20 (Pharmacia Fine Chemicals). HPLC: Tosoh HPLC 8020 apparatus; TSKgel-ODS-120T column
(10 mm, 7.8 mm i.d. ꢂ 30 cm; Tosoh), TSKgel-ODS-80TM column (5 mm, 6.0 mm i.d. ꢂ 15 cm; Tosoh),
and Cosmosil-5SL column (5 mm, 10 mm i.d. ꢂ 25 cm; Nacalai tesque); tR in min. Optical rotation: Jasco-
DIP-360 digital polarimeter. CD Spectra: Jasco J-720 spectropolarimeter; lmax (De) in nm. UV Spectra:
Beckman-DU-64 spectrometer; lmax (log e) in nm. NMR Spectra: Jeol JNM-LA 400 spectrometer; d in
ppm rel. to Me4Si as internal standard, J in Hz. EI-, HR-EI-, FAB-, and HR-FAB-MS: Jeol JMS-DX 303
mass spectrometer; with glycerol as matrix for FAB; in m/z (rel. %).
Plant Material. Leaves of O. fragrans Lour. var. aurantiacus Makino were collected in October 2007,
in Sendai, Miyagi prefecture, Japan, and identified by M. K. A voucher specimen (2007-10-KM2) was
deposited with the laboratory of M. K.
Extraction and Isolation. Fresh leaves of O. fragrans var. aurantiacus (1.3 kg) were extracted with
MeOH (8 l) at r.t. for three weeks. The MeOH extract was concentrated under reduced pressure, and the
residue (195 g) was suspended in H2O. This suspension was successively extracted with CHCl3 (3 ꢂ
600 ml), AcOEt (3 ꢂ 600 ml), BuOH (3 ꢂ 600 ml), and H2O. The BuOH-soluble fraction was
concentrated under reduced pressure to produce a residue. The extract (60 g) was subjected CC
(SiO2; CHCl3/MeOH/H2O 30 :10 :1), and the eluate was separated into Frs. 1 – 4. Fr. 3 was chromato-
graphed on a Sephadex LH-20 column using 50% MeOH, and the eluate was separated into Frs. 3.1 –
3.13. Fr. 3.6 was subjected to prep. HPLC (TSK gel ODS 120T; MeOH/H2O 4 :7; flow rate, 1.5 ml/
min; 408; UV detection at 205 nm) to give ten Peaks 3.6.1 – 3.6.10. Peak 3.6.1 was subjected to prep.
HPLC (TSK gel ODS 80TM; MeOH/H2O 4 :11; flow rate, 1.0 ml/min; 408, UV detection at 205 nm) to
give nine Peaks 3.6.1.1 – 3.6.1.9. Peak 3.6.1.3 was subjected to prep. HPLC (Cosmosil 5SL; CH2Cl2/
MeOH/H2O 70 :10 :1; flow rate, 1.5 ml/min; r.t., detection at 225 nm) to give 9 (28.0 mg; tR 56.4) and 1
(30.5 mg; tR 59.4). Peak 3.6.1.4 was subjected to prep. HPLC (TSK gel ODS 80TM; MeOH/H2O 1:5;
flow rate, 1.0 ml/min; 408; detection at 205 nm) to give two Peaks 3.6.1.4.1 – 3.6.1.4.2. Peak 3.6.1.4.1 was
subjected to prep. HPLC (Cosmosil 5SL; CH2Cl2/MeOH/H2O 70 :10 :1; flow rate, 1.5 ml/min; r.t.;
detection at 225 nm) to give 4 (20.0 mg; tR 60.9) and 8 (18.0 mg; tR 73.2). Peak 3.6.1.4.2 was subjected to
prep. HPLC (Cosmosil 5SL; CH2Cl2/MeOH/H2O 70 :10 :1; flow rate, 1.5 ml/min; r.t.; detection at
225 nm) to give 5 (13.5 mg; tR 58.8) and 13 (22.5 mg; tR 64.8). Peak 3.6.1.5 was subjected to prep. HPLC
(TSK gel ODS 80TM; MeOH/H2O 1:5; flow rate, 1.0 ml/min; 408; detection at 205 nm) to give 2
(18.5 mg; tR 54.5) and 3 (15.0 mg; tR 60.0). Peak 3.6.1.7 was subjected to prep. HPLC (Cosmosil 5SL;
CH2Cl2/MeOH/H2O 70 :10 :1; flow rate, 1.5 ml/min; r.t.; detection at 225 nm) to give 7 (38.0 mg; tR 42.6).
Peak 3.6.1.8 was subjected to prep. HPLC (Cosmosil 5SL; CH2Cl2/MeOH/H2O 70 :10 :1; flow rate,
1.5 ml/min; r.t.; detection at 225 nm) to give 14 (23.0 mg; tR 88.2). Peak 3.6.1.9 was subjected to prep.
HPLC (Cosmosil 5SL; CH2Cl2/MeOH/H2O 70 :10 :1; flow rate, 1.5 ml/min; r.t.; detection at 225 nm) to
give 6 (35.0 mg; tR 38.4) and 11 (26.0 mg; tR 46.8). Peak 3.6.3 was subjected to prep. HPLC (Cosmosil

Helvetica Chimica Acta – Vol. 93 (2010)
2173
5SL; CH2Cl2/MeOH/H2O 60 :10 :1; flow rate, 1.5 ml/min; r.t.; detection at 225 nm) to give 12 (35.0 mg; tR
37.8). Peak 3.6.4 was subjected to prep. HPLC (Cosmosil 5SL; CH2Cl2/MeOH/H2O 60 :10 :1; flow rate,
1.5 ml/min; r.t.; detection at 225 nm) to give 10 (43.0 mg; tR 30.0).
(7S,8R,7’S,8’S)-4,9,4’,7’-Tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 7’-O-b-d-Glucopyranoside
(¼ Tanegoside A ¼ (S)-(4-Hydroxy-3-methoxyphenyl)[(3S,4R,5S)-tetrahydro-5-(4-hydroxy-3-methoxy-
phenyl)-4-(hydroxymethyl)furan-3-yl]methyl O-b-d-Glucopyranoside; 1). Hygroscopic amorphous pow-
der. [a]2D5 ¼ ꢀ28.8 (c ¼ 0.12, MeOH). UV (MeOH): 209 (4.1), 231 (4.1), 280 (3.8). CD (c ¼ 1.5 ꢂ 10ꢀ4 m,
1
MeOH): þ 17.6 (210), þ 4.6 (237), þ 1.8 (285). H- and 13C-NMR (CD3OD): Table 1. FAB-MS: 561
([M þ Na]þ). HR-FAB-MS: 561.1960 ([M þ Na]þ, C26H34NaO1þ2 ; calc. 561.1948).
Enzymatic Hydrolysis of 1. An aq. soln. (5.0 ml) containing 1 (5.0 mg) and cellulase (10 mg) was
incubated at 408 for 4 d. The mixture was extracted with CHCl3 and concentrated to dryness to afford
(7S,8R,7’S,8’S)-4,4’,9,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan (1a; 2.2 mg).
Data of 1a. Hygroscopic amorphous powder. [a]2D5 ¼ þ40.0 (c ¼ 0.15, MeOH). UV (MeOH): 203
(4.5), 228 (4.0), 278 (3.6). CD (c ¼ 3.9 ꢂ 10ꢀ5 m, MeOH): þ 19.9 (205), þ 3.3 (235), þ 1.4 (280).
1H-NMR (CDCl3): 1.94 – 2.01 (m, HꢀC(8)); 2.54 – 2.59 (m, HꢀC(8’)); 3.40 (br. d, J ¼ 5.8, CH2(9)); 4.00
(dd, J ¼ 9.2, 7.7, HAꢀC(9’)); 4.19 (dd, J ¼ 9.2, 4.9, HBꢀC(9’)); 3.84 (s, MeOꢀC(3)); 3.83 (s, MeOꢀC(3’));
4.47 (d, J ¼ 8.2, HꢀC(7)); 4.64 (d, J ¼ 7.2, HꢀC(7’)); 6.77 – 6.89 (m, HꢀC(2,5,6,2’,5’,6’)). EI-MS: 376
(Mþ). HR-EI-MS: 376.1526 (Mþ, C20H24Oþ7 ; calc. 376.1522).
(7S,8R,7’R,8’S)-4,4’,9,7’-Tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 9-O-b-d-Glucopyranoside
(¼{(2S,3R,4S)-Tetrahydro-4-[(R)-hydroxy(4-hydroxy-3-methoxyphenyl)methyl]-2-(4-hydroxy-3-meth-
oxyphenyl)furan-3-yl}methyl b-d-Glucopyranoside; 2). Hygroscopic amorphous powder. [a]2D5 ¼ ꢀ16.7
(c ¼ 0.13, MeOH). UV (MeOH): 205 (4.4), 229 (4.1), 278 (3.7). CD (c ¼ 6.8 ꢂ 10ꢀ5 m, MeOH):, þ 15.2
1
(206), þ 3.5 (235). H- and 13C-NMR (CD3OD): Table 1. FAB-MS: 561 ([M þ Na]þ). HR-FAB-MS:
561.1944 ([M þ Na]þ, C26H34NaO1þ2 ; calc. 561.1948).
Enzymatic Hydrolysis of 2. An aq. soln. (5.0 ml) containing 2 (4.0 mg) and cellulase (10 mg) was
incubated at 408 for 4 d. The mixture was extracted with CHCl3, and concentrated to dryness to afford
(7S,8R,7’R,8’S)-4,4’,9,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan (2a; 2.2 mg).
Data of 2a. Hygroscopic amorphous powder. [a]2D5 ¼ þ35.1 (c ¼ 0.15, MeOH). UV (MeOH): 204
(4.5), 230 (4.0), 279 (3.6). CD (c ¼ 4.5 ꢂ 10ꢀ5 m, MeOH): þ 20.0 (206), þ 5.8 (234). 1H-NMR (CDCl3):
2.25 – 2.32 (m, HꢀC(8)); 2.53 – 2.62 (m, HꢀC(8’)); 3.58 (br. d, J ¼ 9.2, HAꢀC(9’)); 3.63 (dd, J ¼ 10.6, 5.7,
HAꢀC(9)); 3.65 (dd, J ¼ 9.2, 5.8, HBꢀC(9’)); 3.74 (dd, J ¼ 10.6, 3.4, HBꢀC(9)); 3.89 (s, MeOꢀC(3)); 3.90
(s, MeOꢀC(3’)); 4.36 (d, J ¼ 9.2, HꢀC(7)); 4.49 (d, J ¼ 9.6, HꢀC(7’)); 6.80 – 6.93 (m,
HꢀC(2,5,6,2’,5’,6’)). EI-MS: 376 (Mþ). HR-EI-MS: 376.1519 (Mþ, C20H24Oþ7 ; calc. 376.1522).
(7R,8S,7’S,8’R)-4,4’,9,7’-Tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan 9-O-b-d-Glucopyranoside
(¼{(2R,3S,4R)-Tetrahydro-4-[(S)-hydroxy(4-hydroxy-3-methoxyphenyl)methyl]-2-(4-hydroxy-3-meth-
oxyphenyl)furan-3-yl}methyl b-d-Glucopyranoside; 3). Hygroscopic amorphous powder. [a]2D5 ¼ ꢀ12.0
(c ¼ 0.13, MeOH). UV (MeOH): 204 (4.3), 229 (4.0), 278 (3.6). CD (c ¼ 7.9 ꢂ 10ꢀ5 m, MeOH): ꢀ 12.9
1
(205), ꢀ 2.5 (234). H- and 13C-NMR (CD3OD): Table 2. FAB-MS: 561 ([M þ Na]þ). HR-FAB-MS:
561.1945 ([M þ Na]þ, C26H34NaO1þ2 ; calc. 561.1948).
Enzymatic Hydrolysis of 3. An aq. soln. (5.0 ml) containing 3 (4.0 mg) and cellulase (10 mg) was
incubated at 408 for 4 d. The mixture was extracted with CHCl3, and concentrated to dryness to afford
(7R,8S,7’S,8’R)-4,4’,9,7’-tetrahydroxy-3,3’-dimethoxy-7,9’-epoxylignan (3a; 2.0 mg).
Data of 3a. Hygroscopic amorphous powder. [a]2D5 ¼ ꢀ35.7 (c ¼ 0.10, MeOH). UV (MeOH): 204
(4.5), 229 (4.0), 278 (3.6). CD (c ¼ 4.5 ꢂ 10ꢀ5 m, MeOH): ꢀ 20.3 (205), ꢀ 5.2 (235). 1H-NMR (CDCl3):
2.25 – 2.32 (m, HꢀC(8)); 2.53 – 2.62 (m, HꢀC(8’)); 3.58 (br. d, J ¼ 9.2, HAꢀC(9’)); 3.63 (dd, J ¼ 10.6, 5.7,
HAꢀC(9)); 3.65 (dd, J ¼ 9.2, 5.8, HBꢀC(9’)); 3.74 (dd, J ¼ 10.6, 3.4, HBꢀC(9)); 3.89 (s, MeOꢀC(3)); 3.90
(s, MeOꢀC(3’)); 4.36 (d, J ¼ 9.2, HꢀC(7)); 4.49 (d, J ¼ 9.6, HꢀC(7’)); 6.80 – 6.93 (m,
HꢀC(2,5,6,2’,5’,6’)). EI-MS: 376 (Mþ). HR-EI-MS: 376.1519 (Mþ, C20H24Oþ7 ; calc. 376.1522).
(7R,8S,7’R,8’S)-4,9,4’,9’-Tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan 9-O-b-d-Glucopyranoside
(¼ [(2R,3S,4S,5R)-Tetrahydro-2,5-bis(4-hydroxy-3-methoxyphenyl)-4-(hydroxymethyl)furan-3-yl]meth-
yl O-b-d-Glucopyranoside; 4). Hygroscopic amorphous powder. [a]2D5 ¼ ꢀ18.2 (c ¼ 0.12, MeOH). UV
1
(MeOH): 205 (4.5), 231 (4.1), 279 (3.7). CD (c ¼ 5.5 ꢂ 10ꢀ5 m, MeOH): þ 15.0 (208), þ 7.8 (238). H-

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Helvetica Chimica Acta – Vol. 93 (2010)
and 13C-NMR (CD3OD): Table 3. FAB-MS: 561 ([M þ Na]þ). HR-FAB-MS: 561.1960 ([M þ Na]þ,
C26H34NaOþ12 ; calc. 561.1948).
Enzymatic Hydrolysis of 4. An aq. soln. (5.0 ml) containing 4 (5.0 mg) and cellulase (10 mg) was
incubated at 408 for 3 d. The mixture was extracted with CHCl3 and concentrated to dryness to afford
(7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan (4a; 2.0 mg).
Data of 4a. Hygroscopic amorphous powder. [a]2D5 ¼ þ44.8 (c ¼ 0.10, MeOH). UV (MeOH): 204
(4.5), 231 (4.0), 280 (3.6). CD (c ¼ 4.7 ꢂ 10ꢀ5 m, MeOH): þ 10.4 (208), þ 5.2 (238). 1H-NMR (CDCl3):
2.26 – 2.32 (m, HꢀC(8), HꢀC(8’)); 3.66 (dd, J ¼ 10.6, 8.7, HAꢀC(9), HAꢀC(9’)); 3.80 (dd, J ¼ 10.6, 2.9,
HBꢀC(9), HBꢀC(9’)); 3.89 (s, MeOꢀC(3), MeOꢀC(3’)); 4.74 (d, J ¼ 9.2, HꢀC(7), HꢀC(7’)); 6.85 (dd,
J ¼ 8.2, 2.0, HꢀC(6), HꢀC(6’)); 6.90 (d, J ¼ 8.2, HꢀC(5), HꢀC(5’)); 6.94 (d, J ¼ 2.0, HꢀC(2),
HꢀC(2’)). EI-MS: 376 (Mþ). HR-EI-MS: 376.1519 (Mþ, C20H24Oþ7 ; calc. 376.1522).
rel-(7R,8S,7’S,8’R)-4,9,4’,9’-Tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan 9-O-b-d-Glucopyranoside
(¼ rel-[(2R,3S,4R,5S)-Tetrahydro-2,5-bis(4-hydroxy-3-methoxyphenyl)-4-(hydroxymethyl)furan-3-yl]-
methyl O-b-d-glucopyranoside; 5). Hygroscopic amorphous powder. [a]2D5 ¼ ꢀ20.0 (c ¼ 0.15, MeOH).
UV (MeOH): 205 (4.4), 229 (4.0), 278 (3.7). CD (c ¼ 6.6 ꢂ 10ꢀ5 m, MeOH): ꢀ 1.6 (206), ꢀ 0.5 (232),
1
ꢀ 0.4 (272). H- and 13C-NMR (CD3OD): Table 3. FAB-MS: 561 ([M þ Na]þ). HR-FAB-MS: 561.1944
([M þ Na]þ, C26H34NaO1þ2 ; calc. 561.1948).
Enzymatic Hydrolysis of 5. An aq. soln. (5.0 ml) containing 5 (5.0 mg) and cellulase (10 mg) was
incubated at 408 for 3 d. The mixture was extracted with CHCl3, and concentrated to dryness to afford
rel-(7R,8S,7’R,8’S)-4,9,4’,9’-tetrahydroxy-3,3’-dimethoxy-7,7’-epoxylignan (5a; 2.2 mg).
Data of 5a. Hygroscopic amorphous powder. [a]2D5 ¼ꢁ 0.0 (c ¼ 0.10, MeOH). UV (MeOH): 206
(4.6), 231 (4.2), 279 (3.8). CD (c ¼ 4.0 ꢂ 10ꢀ5 m, MeOH): þ 2.5 (204). 1H-NMR (CDCl3): 2.52 – 2.61 (m,
HꢀC(8), HꢀC(8’)); 3.79 (dd, J ¼ 11.6, 2.9, HAꢀC(9), HAꢀC(9’)); 3.87 (s, MeOꢀC(3), MeOꢀC(3’));
3.92 (dd, J ¼ 11.6, 7.7, HBꢀC(9), HBꢀC(9’)); 4.62 (d, J ¼ 7.7, H ꢀC(7), HꢀC(7’)); 6.90 (dd, J ¼ 8.2, 2.4,
HꢀC(6), HꢀC(6’)); 6.94 (d, J ¼ 8.2, HꢀC(5), HꢀC(5’)); 6.97 (d, J ¼ 2.4, HꢀC(2), HꢀC(2’)). EI-MS:
376 (Mþ). HR-EI-MS: 376.1520 (Mþ, C20H24Oþ7 ; calc. 376.1522).
Determination of the Absolute Configuration of the Sugar Residues in Compounds 2 – 5. Each of the
compounds (ca. 1.0 mg) was refluxed with 1m HCl (1 ml) for 5 h. The mixture was neutralized with
Ag2CO3 and filtered. The soln. was concentrated in vacuo and dried to give a sugar fraction. The sugar
fraction was analyzed by HPLC (TSKgel Amide-80; 10 mm, 7.8 mm i.d. ꢂ30 cm; Tosoh column; temp.,
458; MeCN/H2O 4 :1; flow rate 1.0 ml/min; chiral detection (Jasco OR-2090)). Identification of d-glucose
present in the sugar fraction was carried out by the comparison of the tR and [a]D values with those of an
authentic sample; tR [min] 39.0 (d-glucose, pos. [a]D).
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Received February 23, 2010