Structural elucidation and synthesis of vialinin C, a new inhibitor of TNF-α production

Article abstract of DOI:10.1016/j.bmc.2014.02.058

A new inhibitor of TNF-α production (IC₅₀ = 0.89 μM) named vialinin C (1) was isolated from dry fruiting bodies of an edible Chinese mushroom, Thelephora vialis. The structure of 1 was determined by high-resolution MS, NMR spectroscopic analysis, and confirmed by synthesis. Synthesis of ganbajunin B (5) obtained from the same origin was also described.

Full text of DOI:10.1016/j.bmc.2014.02.058

Bioorganic & Medicinal Chemistry 22 (2014) 2442–2446
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Structural elucidation and synthesis of vialinin C, a new inhibitor
of TNF-a production
Yue Qi Ye a,b, Chiemi Negishi b, Yayoi Hongo a, Hiroyuki Koshino a, Jun-ichi Onose b, Naoki Abe b,
,
⇑
Shunya Takahashi a,
⇑
a RIKEN, Wako-shi, Saitama 351-0198, Japan
b Department of Nutritional Science, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new inhibitor of TNF-a production (IC50 = 0.89 lM) named vialinin C (1) was isolated from dry fruiting
Received 31 January 2014
Revised 24 February 2014
Accepted 28 February 2014
Available online 6 March 2014
bodies of an edible Chinese mushroom, Thelephora vialis. The structure of 1 was determined by high-res-
olution MS, NMR spectroscopic analysis, and confirmed by synthesis. Synthesis of ganbajunin B (5)
obtained from the same origin was also described.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
TNF-a
Vialinin C
Vialinin A
Vialinin B
1. Introduction
of its inhibitory activity against TNF-a production and synthesis
of 5 for confirmation of the structure are also discussed.
In the course of our studies on naturally occurring bioactive
compounds contained in edible Chinese mushrooms, we have iso-
lated new p-terphenyl compounds, vialinin A (2)1 and vialinin B
(4)2 along with known compounds, ganbajunin B (5),3 and cyclo-
leucomelone4 from the dry fruiting bodies of Thelephora vialis,
and demonstrated that 2 and 4 were a powerful inhibitor of a tu-
2. Results and discussion
2.1. Isolation and structure elucidation
The dry fruiting bodies (250 g) of Thelephora vialis were ex-
tracted with 80% ethanol, and then filtered. After evaporation of
the whole organic solvent, the remaining aqueous concentrate
was adjusted to pH 3.0 and extracted with ethyl acetate: because
polyphenolic p-terphenyl derivatives, such as vialinin A (2) con-
taining many acidic phenols can be selectively extracted in acidic
conditions. The crude extraction was successively subjected to a
Sephadex LH-20 column chromatography, and then reversed phase
HPLC to give compound 1 (10.5 mg). The molecular formula of 1
was established as C32H20O11 on the basis of high resolution nega-
tive ESIMS data. The IR spectrum of 1 showed the presence of hy-
droxyl and ester carbonyl groups. The UV spectrum closely
resembled those of vialinin B (4) and ganbajunin B (5). The 1H
NMR spectrum of 1 in acetone-d6 and DQF-COSY data revealed
the presence of two aromatic singlet signals at 7.11 and
7.10 ppm for a tetra-substituted benzene ring, and six doublet sig-
nals with 8.8 Hz and each 2H integration values for three sets of
p-substituted phenyl groups at 7.28 (H-20/60) and 6.80 (H-30/50),
7.73 (H-200/600) and 6.77 (H-300/500), and 7.99 (H-2000/6000) and 6.91
(H-3000/5000) ppm, respectively (Table 1). In the 13C-NMR spectrum,
mour necrosis factor (TNF)-
(RBL-2H3) cells: IC50 = 0.09 nM for 2 and 0.05 nM for 4 versus
IC50 = 0.25 nM for FK-506.2,5 TNF-
is a potent multifunctional
a production in rat basophilic leukemia
a
cytokine that mediates a variety of biological actions with a central
role in the pathogenesis of many inflammatory diseases.6–8 Thus,
inhibitors of TNF-
a production in activated mast cells and baso-
philes are promising candidates for a new type of anti-allergic
agent. Recently we developed an advanced analogue with a com-
parable inhibitory activity to that of 29, and conducted to an inves-
tigation to find 2 as a ubiquitin specific peptidase-5 inhibitor.10–12
Compound 213 was also reported as an anticancer active com-
pound from Thelephora aurantiotincta together with a new ana-
logue thelephantin O.14 We continued to search for new
compounds, leading to the discovery of a new dibenzofuran com-
pound named vialinin C (1) (Fig. 1). In this paper, we describe
the isolation, structure elucidation and synthesis of 1. Evaluation
⇑
Corresponding authors. Tel.: +81 484679223; fax: +81 484624627 (S.T.).
E-mail addresses: abe@nodai.ac.jp (N. Abe), shunyat@riken.jp (S. Takahashi).
http://dx.doi.org/10.1016/j.bmc.2014.02.058
0968-0896/Ó 2014 Elsevier Ltd. All rights reserved.

Y. Q. Ye et al. / Bioorg. Med. Chem. 22 (2014) 2442–2446
2443
Figure 2. Summary of HMBC and NOE spectral data of 1.
negative mode ESIMS spectra, characteristic fragment ions at m/z
459 [MꢀHꢀ120(C7H4O2)]ꢀ and 339 [MꢀHꢀ240(C14H8O4)]ꢀ were
observed and supported the presence of two p-hydroxybenzoate
moieties. The remaining NMR signals were quite similar to the sig-
nals of the highly oxygenated dibenzofuran with the p-hydroxy-
phenyl group for the core terphenyl skeleton on 4,2 whose
structure was confirmed by total synthesis.16 HMBC correlations
from two singlet signals (H-6 and H-9) and signals of another
p-hydroxyphenyl group (H-20/60 and H-30/50) are summarised
in Fig. 2. The positions of two p-hydroxybenzoates were deter-
mined by 1D-DPFGSE (double-pulsed-field-gradient-spin-echo)-
NOE experiments.17,18 Sequential NOEs were observed as follows,
between the p-hydroxyphenyl proton signal of the terphenyl por-
tion at 7.28 (H-20/60) ppm and the high-field shifted signal of the
p-hydroxybenzoate at 7.73 (H-200/600) ppm, and between H-200/600
and H-2000/6000 (7.99 ppm) corresponding to two p-hydroxybenzoates
in ortho relationships, and from H-2000/6000 to the singlet signal at
7.10 (H-9) ppm for the 1,2,4,5-tetrasubstituted benzene ring in
the dibenzofuran portion (Fig. 2). On the basis of these spectral
data, the structure of 1 was determined to be 1,2-bis(p-hydrox-
ybenzoyloxy)-3-(4-hydroxyphenyl)dibenzofuran-4,7,8-triol, desig-
nate vialinin C, as shown in Fig. 1. Vialinin C (1) possesses the same
dibenzofuran core structure of 4 with four phenolic hydroxyl
groups. The difference between 4 and 1 is the acyl groups at the
catechol portion at C-1 and C-2. From Thelephore terrestris dibenzo-
furan type p-terphenyl compounds terrestrins E-G with triacyl
groups like 5 were isolated.13 Several dibenzofuran p-terphenyl
derivatives with acetoxy or methoxy groups were also isolated as
biologically active fungal metabolites.19–23 The structural feature
with di-p-hydroxybenzoate moiety in the ortho relationship of 1
is similar to thelephantin G (3).15
Figure 1. Structures of vialinin C (1) and its related compounds.
Table 1
1H NMRa and 13C NMRb data (d) for 1 in acetone-d6
Position
1Hc
13C
1
2
3
4
4a
5a
6
7
8
—
—
—
—
—
—
7.11 s
138.4d
137.7d
122.0
130.1d
143.6d
151.9
99.1
—
—
7.10 s
—
—
—
7.28 d (8.8)
6.80 d (8.8)
—
—
7.73 d (8.8)
6.77 d (8.8)
—
—
147.5
143.0
107.3
115.0
119.5
124.6
132.7
115.7
157.6
121.1
132.9
115.9
162.9
164.8
120.8
133.2
116.4
163.3
164.3
9
9a
9b
10
20(60)
30(50)
40
100
200(600)
300(500)
400
700
1000
—
2000(6000
3000(5000
4000
)
)
7.99 d (8.8)
6.91 d (8.8)
—
—
2.2. Synthesis
7000
Our recent studies on natural p-terphenyls revealed that it was
not easy to determine the structure, in particular, the position of
the hydroxyl groups in these molecules, by NMR analyses
only.15,24,25 Several papers have also appeared denoting different
NMR data with regard to one natural product.3,26 For example,
the 1H-NMR data of 5 isolated by us did not match with those re-
ported in the literature.3 These results suggest that the proposed
structure should be confirmed by total synthesis. Therefore, we
planned to synthesise 1 and 5 from the key intermediate 616 in
our total synthesis of 4 (Scheme 1).
According to the method described in Ref. 16, an orthoester 7
was prepared from 6 synthesized by a sequential Suzuki–Miyaura
coupling of three components. After hydrolysis of 7, the resulting
catechol was submitted to esterification by lithium bis(trim-
ethylsilylamide) (LHMDS) and p-benzyloxybenzoyl chloride,27 giv-
ing 8 in good yield (86%). Hydrogenolysis of this with Pd(OH)2 gave
1 (86%). The 1H and 13C NMR data of synthetic 1 were identical to
those of natural 1. On the other hand, synthesis of 5 began
with phenylacetylation of 6. Since the use of organic bases such
a
b
c
600 MHz.
150 MHz.
Numbers in parentheses are J values.
d
Interchangeable.
26 carbon signals were observed, and six carbon signals were over-
lapped and assigned to carbons of the p-substituted phenyl groups
from HSQC data. There were 18 carbons with no attached protons,
further structural information was analysed by HMBC experi-
ments. Three bonds correlations were observed from the deshield-
ed doublet signals at 7.73 (H-200/600) and 7.99 (H-2000/6000) ppm to
ester carbonyl carbons at 164.8 (C-700) and 164.3 (C-7000) ppm to-
gether with the carbons with a hydroxyl group at 162.9 (C-400)
and 163.4 (C-4000) ppm, respectively. Additional three-bond and
two-bond correlations from H-300/500 to C-100(121.1 ppm) and C-400,
and H-3000/5000 to C-1000 (120.8 ppm) and C-4000 confirmed the 13C
NMR assignments and 1H and 13C NMR chemical shifts values
suggested the presence of two p-hydroxybenzoyl groups.15 In the

2444
Y. Q. Ye et al. / Bioorg. Med. Chem. 22 (2014) 2442–2446
leading to an useful information for designing new anti-allergic
drugs.
2.4. Conclusion
We isolated a new p-terphenyl named vialinin C (1) from the
dry fruiting bodies of an edible Chinese mushroom, Thelephora vial-
is. Compound 1 showed weak inhibitory activity (IC50 = 0.89
lM)
against TNF- production from RBL-2H3 cells. The structures of 1
a
and ganbajunin B (5) were unambiguously established by the
synthesis.
3. Experimental
All reactions were carried out under an argon atmosphere, un-
less otherwise noted. Melting points are uncorrected. IR spectra
were recorded with a JASCO VALOR-III spectrophotometer by
ATR method. Proton (1H) and carbon (13C) NMR spectra were ob-
tained using Varian NMR System 500 (500 MHz) or JEOL ECA-600
(600 MHz) spectrometer as solutions in CDCl3 unless otherwise
noted. Chemical shifts are reported in ppm downfield from tetra-
methylsilane with the solvent resonance as the internal standard
(dH 7.26 ppm or dC 77.0 ppm for CDCl3, dH 3.30 ppm or dC
49.0 ppm for CD3OD, and dH 2.04 ppm or dC 29.8 ppm for ace-
tone-d6). ESI-MS spectra were obtained using JEOL JMS-T100LC
Accu TOF mass spectrometer. Column chromatography was per-
formed on Kanto silica gel 60 N (spherical, neutral; 40–100 lm).
Merck precoated silica gel 60 F254 plates, 0.25 mm thickness, was
used for analytical thin-layer chromatography. The solvent ex-
tracts were dried with magnesium sulfate, and the solutions were
evaporated under diminished pressure at 35–40 °C.
3.1. Isolation of vialinin C (1)
The dry fruiting bodies (250 g) of Thelephora vialis were ex-
tracted with 5.0 L of 80% ethanol for 3 days at room temperature,
and then the extracts were filtered. After evaporation in vacuo,
the aqueous concentrate was adjusted to pH 3.0 and extracted with
1.5 L of ethyl acetate. The organic layer was concentrated and gave
26.1 g of the ethyl acetate extract. A part of the extract (10.0 g) was
applied to a Sephadex LH-20 column, eluted with methanol: chlo-
roform (6:4, v/v) and 8 fractions were obtained (Frs. 1–8). The fifth
fraction was purified by a reverse-phase preparative HPLC (Shisei-
Scheme 1. Reagents and conditions: (a) aq AcOH, 60 °C; (b) LHMDS, THF, ꢀ78 °C
and then 4-BnOC6H4COCl, ꢀ78 °C ? rt, 86% (2 steps); (c) H2, Pd(OH)2, EtOAc, rt, 86%
for 1, 30% for 5 (3 steps from 10); (d) n-BuLi, THF, ꢀ78 °C and then phenylacetyl
chloride, ꢀ78 ? 0 °C, 88%; (e) Pb(OAc)4, benzene, 80 °C, 73%; (f) LHMDS, THF,
ꢀ78 °C and then phenylacetyl chloride, ꢀ78 °C ? rt.
do Co. Ltd., CAPCELL PAK C18 UG120 15 mm
u
ꢁ 250 mm) with
as pyridine and triethylamine for the acylation gave unsatisfactory
results, 6 was treated with n-butyllithium at ꢀ78 °C and the result-
ing lithium alkoxide reacted with phenylacetyl chloride, affording
phenylacetate 9 in high yield. Lead tetraacetate (LTA) oxidation
of this proceeded smoothly to afford orthoacetate 10. Exposure of
10 to mild acidic conditions led to the removal of the acetal group,
providing catechol 11 which was successively treated with LHMDS
and phenylacetyl chloride to give 5 after hydrogenolysis in 30%
overall yield. The low yield of 5 was due to the instability of 11 to-
ward basic conditions employed. The 1H and 13C NMR data of syn-
0.15% KH2PO4 (pH 3.5)/acetonitrile (7:3) at the flow rate of
8.8 mL/min, monitoring at 254 nm) to give 1 (10.5 mg) as a brown-
ish amorphous powder; IR (ATR) 3306, 1697, 1604, 1589, 1249,
1226, 1160, 1066 cmꢀ1; UV kmax
(e, methanol) 211 (50700), 263
(45200), 330 (20900) nm; ESIMS (neg.) m/z 579 [MꢀH]ꢀ, 459
[MꢀHꢀC7H4O2]ꢀ, 339 [MꢀHꢀ(C7H4O2) ꢁ 2]ꢀ; HRESIMS (neg.)
m/z 579.0924 [MꢀH]ꢀ, calcd for C32H19O11 579.0927.
3.2. 1,2-Bis((p-benzyloxy)benzoyloxy)-7,8-bis(benzyloxy)-4-
(benzyloxycarbonyloxy)-3-(4-(benzyloxy)phenyl)dibenzo furan
(8)
thetic 5 well matched those of the natural product isolated by us1
13
´
and the reported data by Radulovic et al.
A solution of 7 (104.0 mg, 0.13 mmol) in acetic acid–water
(20:1; 4.2 mL) was stirred at 50 °C for 3 h, concentrated, and co-
evaporated with toluene to give an amorphous solid, which was
employed to the next step without further purification. To a stirred
solution of the above solid in THF (4.0 mL) was added dropwise a
1.0 M solution of lithium bis(trimethylsilylamide) in tetrahydrofu-
ran (0.29 mL, 0.29 mmol) at -78 °C. After 1 h, 4-benzyloxybenzoyl
chloride (160.3 mg, 0.65 mmol) in THF (2 ml) was added at
ꢀ78 °C and the resulting mixture was stirred at ꢀ78 °C for
30 min and at 0 °C ? rt for 1 h. After being quenched with
2.3. Biological activity
The inhibitory activity of 1 against TNF-a production from RBL-
2H3 cells was evaluated. Compound 1 showed an IC50 value of
0.89 M when the analogue compound vialinin B (4) showed
l
0.02 nM. On the other hand, the inhibitory activity of vialinin A
(2) and its p-hydroxybenzoyl analogue, thelephantin G (3) was re-
ported to be comparable (IC50 = 0.25 nM vs 3.5 nM).15 These results
indicate that the p-terphenyl backbone as well as the type of two
ester moieties was very important to the inhibitory activity, thus

Y. Q. Ye et al. / Bioorg. Med. Chem. 22 (2014) 2442–2446
2445
saturated aqueous NH4Cl, the mixture was extracted with ethyl
acetate. The combined organic layers were washed successively
with water, saturated aqueous NaHCO3, water, brine, dried and
concentrated. The residue was chromatographed on silica gel
(n-hexane–ethyl acetate = 10:1 ? 5:1) to afford 8 (126.0 mg, 86%)
as a white solid; IR (ZnSe) 3033, 1735, 1604, 1508, 1453, 1217,
13C NMR (150 MHz, CDCl3): d 169.2, 168.9, 158.6, 152.1, 150.2,
146.2, 144.9, 138.1, 137.0, 136.8, 136.6, 134.2, 132.9, 130.9,
129.4, 128.63, 128.58, 128.54, 128.46, 128.1, 128.0, 127.9, 127.6,
127.5, 127.23, 127.19, 126.8, 123.0, 115.7, 114.7, 113.6, 113.5,
109.1, 107.9, 98.6, 72.3, 71.4, 69.9, 40.8, 21.1; HRESIMS m/z
821.2372 [M+Na]+ (calcd for C50H38O10Na 821.2363).
1163 cmꢀ1 1H NMR (500 MHz, CDCl3): d 8.14 (2H, d, J = 9.0 Hz),
;
7.85 (2H, d, J = 9.0 Hz), 7.48–7.15 (33H, m), 7.11 (1H, s), 7.03 (2H,
d, J = 9.0 Hz), 6.87 (2H, d, J = 8.8 Hz), 6.86 (2H, d, J = 8.8 Hz), 5.26
(2H, s), 5.19 (2H, s), 5.13 (2H, s), 5.05 (2H, s), 4.98 (2H, s), 4.94
(2H, s); 13C NMR (125 MHz, CDCl3): d 164.0, 163.34, 163.25,
162.8, 158.4, 152.4, 152.0, 150.2, 146.1, 145.7, 136.8, 136.7,
136.45, 136.43, 136.0, 135.9, 134.7, 134.6, 132.6, 132.2, 131.2,
131.0, 128.7, 128.65, 128.61, 128.53, 128.49, 128.48, 128.37,
128.32, 128.2, 128.1, 128.0, 127.95, 127.7, 127.5, 127.18, 127.17,
127.15, 123.7, 121.0, 120.7, 119.6, 114.8, 114.5, 114.4, 114.3,
107.6, 98.5, 71.7, 71.3, 70.5, 70.2, 70.0, 69.8; HRESIMS m/z
1187.3655 [M+Na]+ (calcd for C75H56O13Na 1187.3619).
3.6. Preparation of Ganbajunin B (5)
A solution of 10 (95.0 mg, 0.12 mmol) in acetic acid–water
(16:1; 8.5 mL) was stirred at 50 °C for 3 h, concentrated, and co-
evaporated with toluene to give 11 as an amorphous solid, which
was employed to the next step without further purification. To a
stirred solution of the above solid in THF (4.0 mL) was added drop-
wise a 1.0 M solution of lithium bis(trimethylsilylamide) in tetra-
hydrofuran (0.30 mL, 0.30 mmol) with stirring at ꢀ78 °C. After
1 h, phenylacetyl chloride (0.08 ml, 0.60 mmol) was added at
ꢀ78 °C and the resulting mixture was stirred at ꢀ78 °C for
30 min and at 0 °C ? rt for 14 h. After being quenched with satu-
rated aqueous NH4Cl, the resulting mixture was extracted with
ethyl acetate. The combined organic layers were washed succes-
sively with water, saturated aqueous NaHCO3, water, brine, dried
and concentrated. The residue was passed through a short column
of silica gel (benzene–dichloromethane–n-hexane = 2:2:1) to af-
ford an amorphous solid (74.8 mg) which was dissolved in ethyl
acetate (6.0 ml). To this solution was added palladium hydroxide
(15.0 mg). The mixture was stirred vigorously under a hydrogen
atmosphere at rt for 14 h, filtered through a filter paper under N2
atmosphere, and then concentrated. The residue was purified by
preparative TLC (dichloromethane–methanol = 20:1) under N2
atmosphere to give 5 (19.8 mg, 30%) as an amorphous solid; IR
3.3. Preparation of vialinin C (1)
To a stirred solution of 8 (51.0 mg, 43.8 lmol) in ethyl acetate–
THF (1:1, 4.0 mL) was added palladium hydroxide (15.0 mg). The
mixture was stirred vigorously under a hydrogen atmosphere at
rt for 13.5 h, filtered through a filter paper under N2 atmosphere,
and then concentrated. The residue was chromatographed on silica
gel (dichloromethane–methanol = 10:1) to give 1 (21.9 mg, 86%) as
a white solid; HRESIMS m/z 603.0891 [M+Na]+ (calcd for C32H20-
O11Na 603.0903).
3.4. 7,8-Bis(benzyloxy)-3-(4-(benzyloxy)phenyl)-1,2-methylene
dioxy-4-(phenylacetyloxy)dibenzofuran (9)
(ZnSe) 3364, 3031, 1735, 1100, 1071, 992 cmꢀ1
;
1H NMR
(500 MHz, CD3OD): d 7.44–7.39 (4H, m), 7.34–7.31 (1H, m), 7.24–
7.20 (6H, m), 7.08–7.04 (3H, m), 7.00 (1H, s), 6.91–6.89 (4H, m),
6.66 (2H, d, J = 8.5 Hz), 3.90 (2H, s), 3.74 (2H, s), 3.18 (2H, s); 13C
NMR (150 MHz, CD3OD): d 170.74, 170.68, 170.1, 158.6, 152.7,
148.8, 147.2, 144.3, 137.2, 134.9, 134.6, 134.5, 134.4, 132.14,
132.12, 130.8, 130.3, 130.0, 129.5, 128.7, 128.4, 128.1, 123.5,
120.4, 116,2, 114.1, 107.6, 99.2, 41.4, 41.2, 40.8; HRESIMS m/z
717.1702 [M+Na]+ (calcd for C42H30O10Na 717.1737).
To a stirred solution of 6 (55.0 mg, 88.3 mmol) in THF (2.0 mL)
was added dropwise
a 1.59 M of n-butyllithium (0.07 mL,
111.3 mmol) in n-hexane at ꢀ78 °C. After 15 min, phenylacetyl
chloride (0.02 mL, 115.1 mmol) was added and the mixture was
stirred at ꢀ78 °C for 30 min and 0 °C for 1 h. After addition of
ice-water, the resulting mixture was stirred for 30 min, and then
extracted with ethyl acetate. The combined organic layers were
washed successively with water, saturated aqueous NaHCO3,
water, brine, dried and concentrated. The residue was chromato-
graphed on silica gel (n-hexane–ethyl acetate = 20:1) to give 9
(57.3 mg, 88%) as a white solid; IR (ZnSe) 3032, 1751, 1456,
Acknowledgments
This work was supported by the Chemical Genomics Project
(RIKEN) and in part by JSPS KAKENHI Grant Number 24580168.
N.A. acknowledges the Advanced Research Project of Tokyo
University of Agriculture.
1296, 1253, 1187 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.51–7.21
;
(23H, m), 7.10 (1H, s), 6.92 (2H, d, J = 8.8 Hz), 6.11 (2H, s), 5.23
(2H, s), 5.21 (2H, s), 5.09 (2H, s), 3.82 (2H, s); 13C NMR
(125 MHz, CDCl3): d 169.4, 158.4, 152.1, 150.0, 146.0, 144.4,
140.7, 137.1, 137.0, 136.9, 136.7, 133.1, 130.9, 129.4, 128.63,
128.58, 128.52, 128.46, 128.03, 127.98, 127.88, 127.6, 127.5,
127.3, 127.1, 125.9, 123.7, 115.4, 114.6, 114.0, 108.8, 108.0,
102.1, 98.7, 72.4, 71.5, 70.0, 40.8; HRESIMS m/z 763.2282
[M+Na]+ (calcd for C48H36O8Na 763.2308).
Supplementary data
Supplementary data (NMR data of compounds 1, 5, and 8–10)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.bmc.2014.02.058.
3.5. 1,2-(Acetoxymethylenedioxy)-7,8-bis(benzyloxy)-4-
(phenylacetyloxy)-3-(4-(benzyloxy)phenyl)dibenzofuran (10)
References and notes
1. Xie, C.; Koshino, H.; Esumi, Y.; Takahashi, S.; Yoshikawa, K.; Abe, N. Biosci.
Biotechnol. Biochem. 2005, 69, 2326.
A mixture of 9 (122.3 mg, 0.17 mmol) and lead tetraacetate
(146.4 mg, 0.33 mmol) in benzene (4.0 mL) was stirred at 80 °C
for 5 h. After being cooled to rt, the reaction mixture was filtered
through a pad of Celite, and concentrated. The residue was chro-
matographed on silica gel (n-hexane–ethyl acetate = 20:1 ? 10:1)
to give 10 (96.8 mg, 73%) as an amorphous solid; IR (ZnSe) 3050,
2. Xie, C.; Koshino, H.; Esumi, Y.; Onose, J.; Yoshikawa, K.; Abe, N. Bioorg. Med.
Chem. Lett. 2006, 16, 5424.
3. Hu, L.; Gao, J. M.; Liu, J. K. Helv. Chim. Acta 2001, 84, 3342.
4. Jagers, E.; Hillen-Maske, E.; Steglich, W. Z. Naturforsch. 1987, 42b, 1349.
5. Onose, J.; Xie, C.; Ye, Y.-Q.; Takahashi, S.; Koshino, H.; Yasunaga, K.; Abe, N.;
Yoshikawa, K. Biol. Pharm. Bull. 2008, 31, 831.
6. Vassalli, P. Annu. Rev. Immunol. 1992, 10, 411.
7. Sieper, J.; Braun, J. Expert Opin. Emerg. Drugs 2002, 2, 235.
8. Holgate, S. T. Cytokine 2004, 28, 152.
1750, 1559, 1521, 1508, 1296, 1250 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d 8.03 (1H, s), 7.67–7.37 (24H, m), 7.07 (2H, d, J = 8.8 Hz),
5.37 (2H, s), 5.36 (2H, s), 5.24 (2H, s), 3.98 (2H, s), 2.27 (3H, s);
9. Ye, Y.-Q.; Onose, J.; Abe, N.; Koshino, H.; Takahashi, S. Bioorg. Med. Chem. Lett.
2012, 22, 2385.

2446
Y. Q. Ye et al. / Bioorg. Med. Chem. 22 (2014) 2442–2446
10. Onose, J.; Yoshioka, Y.; Ye, Y.-Q.; Sugaya, K.; Yajima, A.; Taniguchi, K.; Okada,
K.; Yajima, S.; Takahashi, S.; Koshino, H.; Abe, N. Cell. Immunol. 2012, 279,
140.
11. Okada, K.; Ye, Y.-Q.; Taniguchi, K.; Yoshida, A.; Akiyama, T.; Yoshioka, Y.;
Onose, J.; Koshino, H.; Takahashi, S.; Yajima, A.; Abe, N.; Yajima, S. Bioorg. Med.
Chem. Lett. 2013, 23, 4328.
12. Yoshioka, Y.; Ye, Y.-Q.; Okada, K.; Taniguchi, K.; Yoshida, A.; Sugaya, K.; Onose,
J.; Koshino, H.; Takahashi, S.; Yajima, A.; Yajima, S.; Abe, N. PLoS ONE 2013, 8,
e80931.
17. Stott, K.; Stonehouse, J.; Keeler, J.; Hwang, T.-L.; Shaka, A. J. J. Am. Chem. Soc.
1995, 117, 4199.
18. Stott, K.; Keeler, J.; Van, Q. N.; Shaka, A. J. J. Magn. Reson. 1997, 125, 302.
19. Liu, J.-K. Chem. Rev. 2006, 106, 2209.
20. Kaniwa, K.; Ohtsuki, T.; Yamamoto, Y.; Ishibashi, M. Tetrahedron Lett. 2006, 47, 1505.
21. Kaneko, A.; Tsukada, M.; Fukai, M.; Suzuki, T.; Nishio, K.; Miki, K.; Kinoshita, K.;
Takahashi, K.; Koyama, K. J. Nat. Prod. 2010, 73, 1002.
22. Huang, H.; Feng, X.; Xiao, Z.; Liu, L.; Li, H.; Ma, L.; Lu, Y.; Ju, J.; She, Z.; Lin, Y. J.
Nat. Prod. 2011, 74, 997.
13. Radulovic´, N.; Quang, D. N.; Hashimoto, T.; Nukada, M.; Asakawa, Y.
23. Wossa, S. W.; Beekman, A. M.; Ma, P.; Kevo, O.; Barrow, R. A. Asian J. Org. Chem.
2013, 2, 565.
Phytochemistry 2005, 66, 1052.
14. Norikura, T.; Fujiwara, K.; Narita, T.; Yamaguchi, S.; Morinaga, Y.; Iwai, K.;
Matsue, H. J. Agric. Food Chem. 2011, 59, 6974.
24. Ye, Y.-Q.; Koshino, H.; Onose, J.; Yoshikawa, K.; Abe, N.; Takahashi, S. Org. Lett.
2007, 9, 4131.
15. Ye, Y.-Q.; Koshino, H.; Onose, J.; Negishi, C.; Yoshikawa, K.; Abe, N.; Takahashi,
S. J. Org. Chem. 2009, 74, 4642.
25. Ye, Y.-Q.; Koshino, H.; Abe, N.; Nakamura, T.; Hasizume, D.; Takahashi, S. Biosci.
Biotech. Biochem. 2010, 74, 2342.
16. Ye, Y.-Q.; Koshino, H.; Onose, J.; Yoshikawa, K.; Abe, N.; Takahashi, S. Org. Lett.
2009, 11, 5074.
26. Hu, L.; Liu, J. K. Z. Naturforsch. 2003, 58c, 452–454.
27. Cavallito, C. J.; Buck, J. S. J. Am. Chem. Soc. 1943, 65, 2140.