A short semi-synthesis and complete NMR-spectroscopic characterization of the naturally occurring lignan glycoside matairesinol 4,4′-di-O-β-d- diglucoside

Article abstract of DOI:10.1016/j.carres.2010.06.008

A convenient semi-synthesis of (8R,8′R)-matairesinol 4,4′-di-O-β-d-glucopyranoside (MDG), found in the stems of Trachelospermum asiaticum var. intermedium, is described starting from the readily available starting materials d-glucose and hydroxymatairesin

Full text of DOI:10.1016/j.carres.2010.06.008

Carbohydrate Research 345 (2010) 1963–1967
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
A short semi-synthesis andcomplete NMR-spectroscopic characterization of the
naturally occurring lignan glycoside matairesinol 4,40-di-O-b-D-diglucoside
*
Filip S. Ekholm, Patrik Eklund, Reko Leino
Laboratory of Organic Chemistry, Åbo Akademi University, FI-20500 Åbo, Finland
a r t i c l e i n f o
a b s t r a c t
A convenient semi-synthesis of (8R,80R)-matairesinol 4,40-di-O-b-
D-glucopyranoside (MDG), found in the
Article history:
Received 4 May 2010
Received in revised form 9 June 2010
Accepted 15 June 2010
Available online 1 July 2010
stems of Trachelospermum asiaticum var. intermedium, is described starting from the readily available
starting materials -glucose and hydroxymatairesinol. By this approach the synthesis of MDG can be
D
accomplished in six steps with an overall yield of 28%. In addition, the first complete NMR-spectroscopic
characterization of MDG was accomplished by the combination of standard NMR techniques and spectral
simulations performed with the PERCH NMR simulation software.
Keywords:
Lignan glycoside
Ó 2010 Elsevier Ltd. All rights reserved.
Semi-synthesis
NMR spectroscopy
Trachelospermum asiaticum var. intermedium
Lignans, defined as two cinnamic acid residues connected
through a b–b-linkage,1 are a widespread class of natural products
present in plants, trees, and fruits.2 Isolated lignans have been
shown to possess biologically interesting properties including anti-
oxidative, antiestrogenic, and anticarcinogenic activities.3 Due to
their wide occurrence and biological relevance these structures
have also been the target of several total synthesis studies.4 The
previous studies have, however, solely focused on the aglycones
although many of the lignans exist in nature as glycosides. The
neglectance of lignan glycosides may be due to the early isolation
processes where strong acids were used for extraction. The acidic
conditions resulted in the cleavage of glycosidic bonds and, there-
fore, only the deglycosylated aglycones were isolated.5 In recent
years advanced isolation processes have been developed correlat-
ing with an increased number of reports on lignan glycosides.6
Although the structures of many lignan glycosides isolated from
natural sources have been elucidated, reports dealing with their
synthesis are scarce.7 Surprisingly, to our knowledge, lignan glyco-
sides have not been prepared previously by chemical synthesis or
semi-synthetic approaches. A synthetic route to these compounds
is important for a number of reasons: (1) there are several difficul-
ties associated with the isolation of intact lignan glycosides from
natural sources; (2) natural sources seldom provide sufficient
amounts of material for biological evaluation, and (3) by chemical
synthesis a diversity of structural analogues may be prepared for
exploration and comparison of the biological properties of both
natural and unnatural lignans and lignan glycosides.
In this study, (8R,80R)-matairesinol 4,40-di-O-b-
D-glucopyrano-
side (MDG) found in the stems of Trachelospermum asiaticum var.
intermedium8 was selected as the target molecule and was pre-
pared by semi-synthesis. A simple retrosynthetic analysis sug-
gested the construction of this compound from glucose and
hydroxymatairesinol (HMR) (Fig. 1). Such semi-synthetic approach
can be considered appealing with D-glucose being the most abun-
dant biomolecule on earth, whereas (7R,8R,80R)/(7R,8R,80S)-hydrox-
ymatairesinol (HMR) mixture, the major isomer being easily
convertible to (R,R)-matairesinol (MR), is readily available on multi
ton scale from pulp mill side streams.9 In addition to the synthesis
of MDG, its complete characterization by various NMR-spectro-
scopic techniques is reported here in detail for the first time.
Due to the electron-withdrawing properties of the aromatic ring,
phenolic compounds are often considered as difficult glycosylation
targets. Furthermore, steric hindrance from the other substituents
on the aromatic ring contributes to the difficulties associated with
aromatic O-glycosylation. Electron-rich aromatic aglycons are pref-
erably glycosylated under acidic conditions with anomeric acetates
or trichloroacetimidates (TCA).10 Since the TCA-donors are generally
more reactive than the anomeric acetates, they were selected as gly-
cosyl donors for the present study.11 In the literature, mainly acety-
lated TCA-donors have been utilized. In our hands, however, the
acetyl group at C-2 is occasionally activated and transferred to the
acceptor molecule under the reaction conditions employed thereby
decreasing the yield of the desired product. Similar effects have also
been witnessed and reported previously.12 By replacing the acetyl
groupswithbenzoylgroupssuchside reactionscanbe avoided while
retaining the beneficial properties of neighboring group participa-
tion displayed by ester protective groups at C-2.
* Corresponding author. Tel.: +358 2 2154132; fax: +358 2 2154866.
E-mail address: reko.leino@abo.fi (R. Leino).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.06.008

1964
F. S. Ekholm et al. / Carbohydrate Research 345 (2010) 1963–1967
O
H
H
O
H
H
MeO
O
MeO
HO
OH
OH
O
O
O
O
HO
HO
+
HO
HO
HO
OH
HO
HO
OMe
OH
OMe
O
O
OH
HO
HO
1
HO
Figure 1. Retrosynthetic analysis of matairesinol diglucoside.
Synthesis of the benzoylated TCA-donor 2,3,4,6-tetra-O-benzoyl-
-glucopyranose trichloroacetimidate (3) commenced by the lit-
erature procedures and was achieved in three steps from -glucose
with an overall yield of 60%.13 In more detail,
-glucose was fully
benzoylated in quantitative yield using benzoyl chloride and pyri-
dine. The anomeric benzoyl group was selectively removed in 75%
yield with MeNH2 in THF. The benzoylated glucopyranose was then
converted to donor 3 in 80% yield with trichloroacetonitrile and DBU
in CH2Cl2.
HMR is found in exceptionally large concentrations (>10% of dry
weight) in the knots of Norway spruce (Picea abies). In a typical iso-
lation procedure the knots are dried, ground, and extracted with
acetone–water to obtain HMR.9a,c For large-scale isolation, the
HMR–K-acetate adduct can be utilized as described earlier by Freu-
denberg.14 Eklund et al. have previously described the conversion
of HMR to MR in one step in nearly quantitative yield by hydroge-
nation or metal hydride reduction.15 In the present study, the latter
procedure was utilized for the preparation of MR.
With the starting materials at hand, the focus was shifted to the
glycosylation reaction (Scheme 1). Generally, TCA-donors can be
activated by a catalytic amount of Lewis acid.11a,b In many cases,
TMSOTf has been successfully applied as the promoter in glycosyl-
ation reactions and was, accordingly, initially screened also for the
glycosylation of MR.10,16 In our hands, the use of TMSOTf as a pro-
method was desired. In the literature, Et3N has been utilized for
sensitive substrates as a milder alternative in solvent mixtures
containing MeOH/H2O/Et3N (5:1:1).19 An initial screening reaction
at ambient temperature proved unsuccessful using this solvent
combination. By adjusting the proportions of the mixture to
MeOH/THF/H2O:Et3N (5:6:1:2) and heating the reaction mixture
at 55 °C for four days the conversion was found to be complete
as indicated by TLC (MeOH/CH2Cl2 1:3, Rf = 0.26). After purification
of the crude mixture by column chromatography, the product was
isolated in 67% yield. The specific rotation, measured in MeOH in
b-
D
D
D
the present study ([
a
]
D ꢀ19.8), was in good agreement with the va-
lue reported by Nishibe et al. for the isolated native compound
([
a
]
D ꢀ24.0 in EtOH).8 The NMR spectroscopic data reported previ-
ously can, however, not be considered as sufficiently accurate and
thus the complete spectral characterization was carried out in this
study.
The NMR spectroscopic discussion is herein limited to the char-
acterization of MDG, however, similar methods were also applied
to the characterization of its protected precursor. The NMR spectra
of MDG were recorded at 20 °C in order to shift the water signal
which was otherwise overlapping with the anomeric protons.
13
The C NMR signal of 90 (181.4 ppm) was selected as a starting
point for the structural elucidation. The correlations between C-
90–H-70a, C-90–H-70b, C-90–H-8, C-90–H-9a, and C-90–H-9b were
clearly visible by HMBC. By use of COSY and HSQC both the 1H
and 13C chemical shifts of these signals, as well as the signals for
H-80 and C-80, could be determined. Assignation of the aromatic
rings was based on the HMBC correlation between H-7a
(2.62 ppm) and H-7b (2.53 ppm) to C-6 (122.2 ppm) and C-2
(114.0 ppm). The remaining signals from the aromatic ring were
then easily assigned by HMBC and a similar methodology was also
applied for resolving the signals of the second aromatic ring. The
positions of the glucose moieties were determined by HMBC based
on the correlation between C-4 (146.6 ppm) and H-100 (4.87 ppm).
In a similar fashion, the correlation between C-40 and H-1000 was vis-
ible. While the assignation of these signals can be considered fairly
straightforward, the assignation of the carbohydrate moieties of
MDG turned out to be extremely difficult due to severe signal
overlap. For resolving the carbohydrate part, 1D-TOCSY (TOtal
moter resulted in an
a/b-mixture of diglucosylated matairesinol
with moderate conversion (50%). Changing the reaction tempera-
ture (ꢀ50 to 0 °C) or the amount of TMSOTf (0.2–1 equiv) did not
improve the glycosylation selectivity and efficiency. The promoter
was therefore switched to the stronger Lewis acid BF3ꢁOEt2, which
has previously been used with success in similar reactions.10,17
With BF3ꢁOEt2, as the promoter, the reaction proceeded smoothly
under unoptimized reaction conditions to give the desired com-
pound in 69% yield after purification by column chromatography.
For deprotection of benzoyl and ester protective groups in general,
NaOMe in MeOH (Zémplen conditions) is the most commonly em-
ployed procedure.18 In the present study, deprotection under these
conditions gave a mixture of products, probably due to the pres-
ence of the lactone functionality or the slightly acidic a-proton in
the vicinity of this center. Accordingly, a milder deprotection
O
H
O
O
H
H
2' 7'
1'
H
H
8'
MeO
HO
MeO
OBz
MeO
3'
9'
O
O
OH
5'''
O
9
6'''
4'''
6'
7
i
ii
O
O
O
O
8
4'
H
5'
6
1
BzO
BzO
HO
2'''1'''
2
3
HO
3'''
HO
BzO
5
OMe
OMe
OMe
4
1
2
4
O
O
OH
O
BzO
BzO
HO
O
1''
2''
OH
3''
5''
6''
4''
HO
OBz
BzO
HO
Scheme 1. Reagents and conditions for the reactions and numbering of the product: (i) 3, BF3ꢁOEt2, CH2Cl2, 0 °C, 69%; (ii) MeOH/THF/H2O/Et3N (5:6:1:2), 55 °C, 67%.

F. S. Ekholm et al. / Carbohydrate Research 345 (2010) 1963–1967
1965
Correlation SpectroscopY) turned out to be a useful method.20 The
only separable signals were those from the anomeric protons (4.87
and 4.86 ppm) and even their separation was marginal, as shown
rally occurring lignan glycosides are currently ongoing in our lab-
oratory. In future studies we also aim to assess the biological
activities of both MDG and its structural analogues. The results
are expected to provide information about the differences in activ-
ities between isolated lignans vis-á-vis their native lignan
glycosides.
in Figure 2, requiring
a narrow 1D-TOCSY excitation range
achieved by prolonging the pulse and reducing the pulse power.
While the 1D-TOCSY NMR spectra significantly enhanced the
complete assignation, accurate and reliable coupling constants
could not be extracted from the spectral data alone. In our previous
work, we have described the complete spectral assignation of a
b-1,2-linked mannotetraose by use of the NMR simulation soft-
ware PERCH.21,22 The same computer program was utilized here
for the complete assignation of the 1H NMR spectra of MDGs
(Fig. 3). The standard NMR-spectroscopic techniques (1H, 13C,
1D-TOCSY, COSY, HSQC, HMBC, and NOESY NMR) in combination
with the simulation software thus enabled the complete assigna-
tion of MDG both in the protected and in the deprotected form.
To conclude, a method for the preparation of lignan glycosides
has been developed and utilized in the short semi-synthesis of
the naturally occurring lignan glycoside MDG, found in the stems
of Trachelospermum asiaticum var. intermedium. By this approach,
the synthesis of MDG is accomplished in six linear steps, starting
1. Experimental
1.1. General methods
Reaction solvents were dried and distilled prior to use when
necessary. All reactions containing moisture- or air-sensitive re-
agents were carried out under argon atmosphere. The NMR spectra
were recorded with a Bruker Avance NMR spectrometer operating
at 600.13 MHz (1H: 600.13 MHz, 13C: 150.90 MHz). The probe tem-
perature during the experiments was kept at 25 °C unless indicated
otherwise. All products were fully characterized by utilization of
the following 1D-techniques: 1H, 13C and TOCSY in combination
with the following 2D-techniques; DQF-COSY, NOESY, HSQC, and
HMBC by using pulse sequences provided by the manufacturer.
Chemical shifts are expressed on the d scale (in ppm) using TMS
(tetramethylsilane), residual chloroform, or methanol as internal
standards. Coupling constants are given in hertz and provided only
once, when first encountered. Coupling patterns are given as s, sin-
glet; d, doublet; t, triplet; etc. The computational analysis of the 1H
spectra of compounds 1 and 4 was achieved by utilization of the
PERCH NMR software with starting values and spectral parameters
obtained from the various NMR techniques used.22 HRMS were re-
corded using a Bruker Micro Q-TOF with ESI (electrospray ioniza-
tion) operated in positive mode. Optical rotations were measured
at 23 °C, unless otherwise stated, with a Perkin–Elmer polarimeter
equipped with a Na-lamp (589 nm). TLC was performed on alumi-
num sheets precoated with Silica Gel 60 F254 (Merck). Flash
from the readily available starting materials D-glucose and HMR,
with a 28% overall yield. The key features of this method consist
of glycosylation with benzoylated TCA-donors in the presence of
BF3ꢁOEt2 Lewis acid promoter. In addition, the complete NMR spec-
troscopic characterization of MDG is reported and discussed here
in detail for the first time. To our knowledge, this is the first report
on the glycosylation of lignans. For verification of the generality of
this approach to lignan glycosidation, the same method was also
utilized for the glycosylation of MR with benzoylated mannose-
based TCA-donor as well as for glycosylation of a-conidendrin with
benzoylated glucose TCA-donor (for details, see Supplementary
data). Both these reactions proceeded with efficiencies similar to
glucosylation of MR. Efforts toward the preparation of other natu-
Figure 2. 1D-TOCSY NMR spectra of the glucose-moieties of MDG. From the top: Glc000, Glc00 and the whole spectrum.

1966
F. S. Ekholm et al. / Carbohydrate Research 345 (2010) 1963–1967
Figure 3. Spectral simulation of the 1H NMR spectrum of 1 (4.89–2.48 ppm region) with the Perch NMR software: simulated spectrum (top) and observed spectrum (bottom).
chromatography was carried out on Silica Gel 60 (0.040–0.060 mm,
Merck). Spots were visualized by UV followed by charring with 1:4
H2SO4/MeOH and heating.
red at 55 °C for 100 h and concentrated. The crude product was puri-
fied by column chromatography (MeOH/CH2Cl2 1:3) to give the title
compound as a white foam (22 mg, 67%). Rf = 0.26 (MeOH/CH2Cl2
1:3); ½a 3D0
ꢂ
ꢀ19.8 (c 1.00, MeOH). 1H NMR (600.13 MHz, CD3OD,
20 °C): d 7.03 (d, 1H, J5 ,6 = 8.2 Hz, H-50), 7.00 (d, 1H, J5,6 = 8.2 Hz,
0
0
1.2. Syntheses
H-5), 6.72 (d, 1H, J2 ,6 = 2.0 Hz, H-20), 6.62 (d, 1H, J2,6 = 2.0 Hz, H-2),
0
0
6.61 (dd, 1H, H-60), 6.55 (dd, 1H, H-6), 4.87 (d, 1H, J1 ,2 = 7.8 Hz, H-
00 00
1.2.1. (8R,80R)-Matairesinol 4,40-di-2,3,4,6-tetra-O-benzoyl-b-
D-
glucopyranoside (4)
To a solution containing 2 (28 mg, 0.079 mmol), 3 (152 mg,
2.6 equiv), and pre-activated 4 Å MS in dry CH2Cl2 (2.5 ml) was
100), 4.86 (d, 1H, J1
= 7.7 Hz, H-1000), 4.26 (dd, 1H, J9a,8 = 7.4,
000,2000
J9a,9b = ꢀ9.1 Hz, H-9a), 3.99 (dd, 1H, J9b,8 = 6.9 Hz, H-9b), 3.87 (dd,
1H, J6
= 2.3, J6
b = ꢀ12.1 Hz, H-6000a), 3.86 (dd, 1H,
000a,5000
000a,6000
J6 a,5 = 2.2, J6 a,6 b = –12.0 Hz, H-600a), 3.78 and 3.77 (each s, each
00
00
00
00
added BF3ꢁOEt2 (5
ll, 0.5 equiv) at 0 °C. The resulting mixture
3H, 3-OCH3 and 30-OCH3), 3.68 (dd, 1H, J6 b,5 = 5.6 Hz, H-600b), 3.68
(dd, 1H, J6
00
00
was stirred for 1.5–2 h, brought to rt, diluted with CH2Cl2
(20 ml), and washed with satd NaHCO3-solution (20 ml). The or-
ganic phase was dried with Na2SO4, filtered, and concentrated.
The crude product was purified by column chromatography (hex-
ane/EtOAc, 1:1) to give the title compound as a white solid
= 5.7 Hz, H-6000b), 3.50 (dd, 1H, J2 ,3 = 9.4 Hz, H-200),
000,3000
00 00
000b,5000
= 9.4 Hz, H-2000), 3.48 (dd, 1H, J3
= 9.0 Hz, H-
000,4000
3.50 (dd, 1H, J2
3000), 3.48 (dd, 1H, J3 ,4 = 9.1 Hz, H-300), 3.43 (ddd, 1H, J5
= 9.9 Hz,
000,4000
00 00
H-5000), 3.42 (ddd, 1H, J5 ,4 = 9.8 Hz, H-500), 3.40 (dd, 1H, H-400), 3.39
00 00
(dd, 1H, H-4000), 2.92 (dd, 1H, J7 a,8 = 4.9, J7 a,7 b = ꢀ13.9 Hz, H-70a),
0
0
0
0
(83 mg, 69%). Rf = 0.17 (hexane/EtOAc 1:1); ½a D23
ꢂ
+0.0 (c 0.15,
2.92 (dd, 1H, J7 b,8 = 8.2 Hz, H-70b), 2.67 (ddd, 1H, J8 ,8 = 7.4 Hz, H-
80), 2.62 (dd, 1H, J7a,8 = 7.4, J7a,7b = –13.8 Hz, H-7a), 2.53 (dd, 1H,
J7b,8 = 7.9 Hz, H-7b), 2.52 (ddddd, 1H, H-8) ppm.
0
0
0
CHCl3). 1H NMR (600.13 MHz, CDCl3, 25 °C): d 8.01–7.27 (m, 40H,
arom. H), 7.13 (d, 1H, J5 ,6 = 8.1 Hz, H-50), 7.08 (d, 1H, J5,6 = 8.1 Hz,
0
0
H-5), 6.55 (d, 1H, J2 ,6 = 2.0 Hz, H-20), 6.49 (dd, 1H, H-60), 6.30 (d,
0
0
13C NMR (150.9 MHz, CD3OD, 20 °C): d 181.4 (C-90), 150.5 (C-30,
C-3), 146.8 (C-40), 146.6 (C-4), 134.6 (C-1), 134.1 (C-10), 122.9 (C-
60), 122.2 (C-6), 117.7 (C-5), 117.6 (C-50), 114.5 (C-20), 114.0 (C-
2), 102.8 (C-100, C-1000), 78.1 (C-500, C-5000), 77.8 (C-300, C-3000), 74.9
(C-200, C-2000), 73.0 (C-9), 71.4 and 71.3 (C-400, C-4000), 62.5 (C-600, C-
6000), 56.6 (3-OCH3, 30-OCH3), 47.7 (C-80), 42.3 (C-8), 39.1 (C-7),
35.6 (C-70) ppm.
00 00
1H, J2,6 = 2.0 Hz, H-2), 6.29 (dd, 1H, H-6), 6.00 (dd, 1H, J3 ,4 = 9.5,
J3 ,2 = 9.7 Hz, H-300), 5.99 (dd, 1H, J3
= 9.5, J3
= 9.7 Hz, H-3000),
00 00
0
00
000,4000
000,2000
= 7.8 Hz, H-2000), 5.79 (dd, 1H, J2 ,1 = 7.8 Hz, H-
000,1000
5.79 (dd, 1H, J2
200), 5.74 (dd, 1H, J4
= 9.9 Hz, H-4000), 5.73 (dd, 1H, J4 ,5 = 9.9 Hz,
000,5000
00 00
H-400), 5.22 (d, 1H, H-1000), 5.20 (d, 1H, H-100), 4.65 (dd, 1H,
b = –12.1 Hz, H-6000a), 4.64 (dd, 1H, J6 a,5 = 3.1,
000a,5000
000a,6000
00
00
J6
= 3.2, J6
J6 a,6 b = –12.1 Hz, H-600a), 4.54 (dd, 1H, J6 b,5 = 5.9 Hz, H-600b),
00
00
00
00
HRMS: calcd for
705.2331.
C
32H42O16Na [M+Na]+ 705.2371; found
4.52 (dd, 1H, J6
= 5.9 Hz, H-6000b), 4.23 (ddd, 1H, H-500), 4.22
000b,5000
(ddd, 1H, H-5000), 4.00 (dd, 1H, J9a,8 = 7.4, J9a,9b = –9.2 Hz, H-9a),
3.75 (dd, 1H, J9b,8 = 7.8 Hz, H-9b), 3.30 (s, 3H, 30-OCH3), 3.27 (s,
Acknowledgments
3H, 3-OCH3), 2.91 (dd, 1H, J7 a,8 = 5.1, J7 a,7 b = –14.1 Hz, H-70a),
0
0
0
0
2.81 (dd, 1H, J7 b,8 = 7.3 Hz, H-70b), 2.50 (dd, 1H, J7a,8 = 6.2,
0
0
Financial support from the Academy of Finland (projects #
121334 and 121335) is gratefully acknowledged. The authors
thank Monika Poláková (Slovak Academy of Sciences), Rainer Sjö-
holm (Åbo Akademi University), and Chinmoy Mukherjee (Åbo
Akademi University) for fruitful discussions and Markku Reunanen
(Åbo Akademi University) for HRMS analyses.
J7a,7b = –14.1 Hz, H-7a), 2.48 (ddd, 1H, J8 ,8 = 7.8 Hz, H-80), 2.36
0
(ddddd, 1H, J8,7b = 9.0 Hz, H-8), 2.35 (dd, 1H, H-7b) ppm.
13C NMR (150.9 MHz, CDCl3, 25 °C): d 178.3 (C-90), 166.0 (600-
OCOPh, 6000-OCOPh), 165.8 (300-OCOPh, 3000-OCOPh), 165.2 (200-
OCOPh, 2000-OCOPh), 165.1 (400-OCOPh, 4000-OCOPh), 150.9 (C-30, C-
3), 145.0 (C-40), 144.9 (C-4), 134.5 (C-1, C-10), 133.5–128.3 (arom.
C), 121.1 (C-60), 121.0 (C-5), 120.8 (C-50), 120.3 (C-6), 113.2 (C-
20), 112.7 (C-2), 101.6 (C-1000), 101.5 (C-100), 72.6 (C-300, C-3000), 72.4
(C-500, C-5000), 71.7 (C-200, C-2000), 71.0 (C-9), 69.7 (C-400, C-4000), 63.1
(C-600, C-6000), 55.4 (3-OCH3, 30-OCH3), 46.4 (C-80), 41.0 (C-8), 38.3
(C-7), 34.7 (C-70) ppm.
Supplementary data
Supplementary data (spectral data of all structures and experi-
mental data on the glycosylation of a-conidendrin and matairesi-
nol with TCA-donors) associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.06.008.
HRMS: calcd for
1537.4425.
C
88H74O24Na [M+Na]+ 1537.4468; found
References
1.2.2. (8R,80R)-Matairesinol 4,40-di-O-b-
D-glucopyranoside (1)
Compound 4 (73 mg, 0.048 mmol) was dissolved in a mixture
containing MeOH/THF/H2O/Et3N (5:6:1:2) and the solution was stir-
1. (a) Haworth, R. D. Ann. Reports Prog. Chem. (Chem. Soc. London) 1936, 33, 266;
(b) Haworth, R. D. Nature 1941, 147, 225.

F. S. Ekholm et al. / Carbohydrate Research 345 (2010) 1963–1967
1967
2. See, for example: (a) Jin, J.-S.; Hattori, M. J. Agric. Food Chem. 2009, 57, 7537; (b)
Meagher, L. P.; Beecher, G. R.; Flanagan, V. P.; Li, B. W. J. Agric. Food Chem. 1999,
47, 3173; (c) Ekman, R. Holzforschung 1976, 30, 79.
11. (a) Fairbanks, A. J.; Seward, C. M. P. In Carbohydrates; Osborn, H., Ed.; Academic
Press: Oxford, 2003; pp 147–165; (b) Stick, R. V. Carbohydrates: The Sweet
Molecules of Life; Academic Press: London, 2001; (c) Kröger, L.; Thiem, J. J.
Carbohydr. Chem. 2003, 22, 9; (d) Burger, K.; Kluge, M.; Koksch, B.; Fehn, S.;
Böttcher, C.; Hennig, L.; Müller, G. Heterocycles 2004, 64, 143.
12. See, for example: (a) Lemieux, R. U. Chem. Can. 1964, 16, 14; (b) Garegg, P. J.;
Norberg, T. Acta Chem. Scand. 1979, 33, 116; (c) Uvarova, N. I.; Oshitok, G. I.;
Elyakov, G. B. Carbohydr. Res. 1973, 27, 79.
3. See, for example: (a) Suja, K. P.; Jayalekshmy, A.; Arumughan, C. J. Sci. Food
Agric. 2005, 85, 1779; (b) Fauré, M.; Lissi, E.; Torres, R.; Videla, L. A.
Phytochemistry 1990, 29, 3773; (c) Setchell, K. D. R.; Adlercreutz, H. In Role of
the Gut Flora Toxicity and Cancer, Mammalian Lignans amd Phytoestrogens:
Recent Study on the Formation. Metabolism and Biological Role in Health and
Disease; Rowland, I. R., Ed.; Academic Press: London, 1988; pp 315–345; (d)
Castro, M. A.; Miguel del Corral, J. M.; Gordaliza, M.; Gómez-Zurita, M. A.;
García, P. A.; San Feliciano, A. Phytochem. Rev. 2003, 2, 341.
13. Brimble, M. A.; Kowalczyk, R.; Harris, P. W. R.; Dunbar, P. R.; Muir, V. J. Org.
Biomol. Chem. 2008, 6, 112.
14. Freudenberg, K.; Knof, L. Chem. Ber. 1957, 2857.
4. See, for example: (a) Baran, P. S.; DeMartino, M. P. Angew. Chem., Int. Ed. 2006,
45, 7083; (b) Roy, S. C.; Rana, K. K.; Guin, C. J. Org. Chem. 2002, 67, 3242; (c)
Wang, C. L. J.; Ripka, W. C. J. Org. Chem. 1983, 48, 2555; (d) Boissin, P.; Dahl, R.;
Brown, E. Tetrahedron Lett. 1989, 30, 4371.
5. Ayres, D. C.; Loike, J. D. Lignans, Chemical, Biological and Clinical Properties;
Cambridge University Press: Cambridge, 1990. pp 144–145.
15. (a) Eklund, P.; Lindholm, A.; Mikkola, J.-P.; Smeds, A.; Lehtilä, R.; Sjöholm, R.
Org. Lett. 2003, 5, 491; (b) Eklund, P.; Sundell, F. J.; Smeds, A.; Sjöholm, R. Org.
Biomol. Chem. 2004, 2, 2229.
16. (a) Mahling, J.-A.; Schmidt, R. R. Synthesis 1993, 325; (b) Hasuoka, A.;
Nakayama, Y.; Adachi, M.; Kamiguchi, H.; Kmaiyama, K. Chem. Pharm. Bull.
2001, 49, 1604.
6. (a) Huo, C.; Liang, H.; Zhao, Y.; Wang, B.; Zhang, Q. Phytochemistry 2008, 69,
788; (b) Kanchanapoom, T.; Chumsri, P.; Kasai, R.; Otsuka, H.; Yamasaki, K.
Phytochemistry 2003, 63, 985; (c) Guan, S.; Xia, J.; Lu, Z.; Chen, G.; Jiang, B.; Liu,
X.; Guo, D. Magn. Reson. Chem. 2008, 46, 186; (d) Day, S.-H.; Chiu, N.-Y.; Tsao, L.-
T.; Wang, J.-P.; Lin, C.-N. J. Nat. Prod. 2000, 63, 1560.
17. See, for example: (a) Yu, B.; Zhang, Y.; Tang, P. Eur. J. Org. Chem. 2007, 5145; (b)
Wei, G.; Yu, B. Eur. J. Org. Chem. 2008, 3156.
18. (a) Zemplén, G.; Gerecs, A.; Hadácsy, I. Chem. Ber. 1936, 69, 1827; (b) Robertson,
J.; Stafford, P. M. In Carbohydrates; Osborn, H., Ed.; Academic Press: Oxford,
2003; pp 22–67.
7. Eklund, P.; Holmström, T.; Al-Ubaydy, L.; Sjöholm, R.; Hakala, J. Tetrahedron
Lett. 2006, 47, 1645.
19. Tsuzuki, K.; Nakajima, Y.; Watanabe, T.; Yanagiya, M.; Matsumoto, T.
Tetrahedron Lett. 1978, 989.
8. Nishibe, S.; Hisada, S.; Inagaki, I. Can. J. Chem. 1973, 51, 1050.
9. (a) Eckerman, C.; Holmbom, B. PCT WO 0209893 A1, 2001; (b) Sierks,
M.; Svensson, B. U.S. Patent 51,62,210, 1992; (c) Holmbom, B.;
Eckerman, C.; Eklund, P.; Hemming, J.; Nisula, L.; Reunanen, M.;
Sjöholm, R.; Sjöholm, R.; Sundsberg, A.; Sundberg, K.; Willför, S.
Phytochem. Rev. 2003, 2, 331.
20. See, for example: (a) Lambert, J. B.; Mazzola, E. P. Nuclear Magnetic Resonance
Spectroscopy, An Introduction to Principles, Applications and Experimental
Methods; Prentice Hall: New Jersey, 2004; (b) Berger, S.; Braun, S. 200 and
More NMR Experiments; Wiley-VCH: Weinheim, 1998. pp 488–491.
21. Ekholm, F. S.; Sinkkonen, J.; Leino, R. New J. Chem. 2010, 34, 667.
22. (a) Laatikainen, R.; Niemitz, M.; Weber, U.; Sundelin, J.; Hassinen, T.;
10. For a review see: Jacobsson, M.; Malmberg, J.; Ellervik, U. Carbohydr. Res. 2006,
341, 1266.
Vepsäläinen, J. J. Magn. Reson., Ser
information on the software, see: http://www.perchsolutions.com.
A 1996, 120, 1–10; (b) For detailed