Syntheses of all-methylated ellagitannin, isorugosin B and rugosin B

Article abstract of DOI:10.1016/j.tet.2011.01.004

Ellagitannins possess a wide range of biological activities and remarkable structural diversity, which commonly include an axially chiral biaryl unit. This paper describes syntheses of all-methylated versions of isorugosin B and rugosin B, which are regio

Full text of DOI:10.1016/j.tet.2011.01.004

Tetrahedron 67 (2011) 1960e1970
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Tetrahedron
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Syntheses of all-methylated ellagitannin, isorugosin B and rugosin B
Kazuma Shioe a, Yusuke Sahara b, Yoshikazu Horino a, Takashi Harayama b, Yasuo Takeuchi b,
,
Hitoshi Abe a
*
a Graduate School of Science and Engineering, University of Toyama, Toyama 930-8555, Japan
b Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Ellagitannins possess a wide range of biological activities and remarkable structural diversity, which
commonly include an axially chiral biaryl unit. This paper describes syntheses of all-methylated versions
of isorugosin B and rugosin B, which are regioisomeric, ellagitannin-related compounds. The key features
of these syntheses involve the construction of an axially chiral biaryl function on a sugar moiety through
a Pd-catalyzed intramolecular biaryl coupling reaction, Bringmann’s atroposelective lactone opening
reaction, and a two-step ester formation. This is the first synthetic approach for generating ellagitannins
featuring a valoneoyl group.
Received 13 November 2010
Received in revised form 24 December 2010
Accepted 4 January 2011
Available online 9 January 2011
Keywords:
Natural product
Ellagitannin
Axial chirality
Palladium
Ó 2011 Elsevier Ltd. All rights reserved.
Regioisomer
1. Introduction
ellagitannins,5 was chosen as the initial synthetic target. Despite
being an important structural component of the ellagitannin fam-
Ellagitannins are polyphenolic natural products with a wide range
of biologicalactivities, includingantioxidant, antivirus, and antitumor
activities. This class of compounds may therefore be useful in me-
dicinalapplications.1 Additionally, several researchers have expressed
an interest in the structural diversity within this class of compounds
with particular emphasis on those structures exhibiting axially chiral
biaryl components.2 Effective methods for constructing axially chiral
biaryl moieties have been developed3 and syntheses of several ella-
gitannins involving biaryl units with C2 symmetry, such as corilagin,
sanguiin H-5, and coriariin A, have been demonstrated.4 However,
non-symmetric biaryl components have yet to be synthesized. The
valoneoyl group (Fig. 1) is a significant structural component of ella-
gitannins5 since the ellagitannins, which possess this structure
indicates unique bioactivity. In particular, oenothein B6 exhibits
strong antitumor activity, based on potentiation of the host immune
defense.7 For this reason, the development of efficient strategies for
constructing valoneoyl groups is important for syntheses involving
this class of natural ellagitannins in new drug discovery.
ily, an asymmetric synthesis of 1 has not previously been reported.8
Axial chirality was generated using Bringmann’s ‘lactone concept,’
which is an effective method for synthesizing axially chiral biaryl-
type natural products.9 It was thus expected that this technique
would be applicable to the synthesis of hexadecamethyl derivatives
of isorugosin B (2)5d,5e and rugosin B (3),5f which are the corre-
sponding regioisomeric ellagitannins.
The current study demonstrates the first reported synthesis of
valoneoyl-containing ellagitannins through the enantioselective
construction of trimethyl octa-O-methyl valonate (1) and the
syntheses of all-methylated versions of isorugosin B (2) and
rugosin B (3).10
2. Results and discussion
2.1. Enantioselective synthesis of trimethyl octa-O-methyl
valonate 1
The synthetic strategy described here is based on the initial
construction of a valoneoyl group with subsequent attachment to
a suitable glucose core. Trimethyl octa-O-methyl valonate (1),
which has been frequently identified in structural determination of
The initial synthetic outline of 1 is depicted in Scheme 1. The
target molecule 1 was synthesized from the six-membered ring
lactone 4 using Bringmann’s ‘lactone concept’ to forge the axially
chiral biaryl components through a series of functional group ma-
nipulations. In this way, lactone 4 is a key intermediate in the
synthesis. A Pd-catalyzed intramolecular biaryl coupling reaction11
is presumably a useful method for the formation of 4, which
* Corresponding author. E-mail address: abeh@eng.u-toyama.ac.jp (H. Abe).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.004

K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1961
OH
OH
HO
OH
O
HO
OH
OH
OH
HO
HO
CO O
CO O
O
O
HO
HO
CO
CO
OH
OC
O
G
HO
HO
HO
HO
HO
HO
O
HO
O
O
O
O
CO
OC
OC
OH
OH
O
CO
OR
OR
OR
O
G =
G
OH
O
OH
OH
OH
Valoneoyl group
Oenothein B : R = H
OR
OMe
OR
MeO
RO
RO
RO
RO
MeO
MeO
CO2Me
CO2Me
RO
RO
CO O
CO O
CO2R
O
O
O
OR'
O
G
MeO
MeO
MeO
RO
RO
RO
G
O
O
RO
RO
CO O
CO O
O
O
CO2Me
CO2R
OR'
O
G
RO
G
OMe
OR
OR
Trimethyl
Isorugosin B : R = R' = H
Rugosin B : R = R' = H
octa-O-methylvalonate 2 : R = Me, OR' = α-OMe
(1)
3 : R = Me, OR' = α-OMe
Fig. 1. Examples of valoneoyl-containing ellagitannins and its related compounds.
OMe
OMe
OMe
OMe
OMe
MeO
O
OMe
O
MeO
MeO
CO2Me
CO2Me
OMe
CO2Me [Pd]
Bringmann's
X
O
MeO
MeO
MeO
O
MeO
MeO
MeO
CO2Me
CO2Me
‘lactone concept’
MeO
MeO
MeO
O
O
O
CO2Me
CO2Me
OMe
1
OMe
4
OMe
5
OMe
BnO
CO2Me
OMe
OMe
HO
MeO
MeO
MeO
CO2Me
CO2Me
MeO
HOOC
OH
+
Br
8
X
6
O
MeO
MeO
CO2Me
OMe
7
9
OMe
Scheme 1. Synthetic outline of 1.

1962
K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
requires ester 5 as a precursor. Ester 5 can be obtained by a simple
esterification between the corresponding carboxylic acid 612 and
phenol 7. Phenol 7 can be prepared by an Ullmann-type coupling13
of phenol 814 and bromide 9.15
of the two acetoxy groups produced the triol 17. A final two-step
oxidation of three hydroxy groups and methylation of the resulting
carboxylic acids gave compound 1. The absolute configuration of the
synthetic material was determined by comparing the sign of optical
rotation with that in previously reported data.18 The stereo-
selectivity of the asymmetric reduction could be explained by the
Bringmann’s model.9 The above procedure was successful in pro-
ducing (S)-1.
The synthesis of 1 began with the preparation of the biaryl ether
10 through an Ullmann condensation of phenol 8,14 which was
obtained from commercially available methyl gallate according to
a previously reported method, and bromide 915 (Scheme 2).
Deprotection under hydrogenolysis conditions provided phenol 7,
which underwent esterification with carboxylic acid 612 using EDC
to afford ester 5 as a precursor of the intramolecular biaryl coupling
reaction. However, all attempts to prepare the coupling product 4
were unsuccessful. This result is similar to previous results,16 in
which the electron-withdrawing properties of the ester group
adjacent to the reacting position interfered with the Pd-mediated
biaryl coupling reaction.
2.2. Syntheses of methylated ellagitannins
Given the success of the above synthesis, the strategy was ex-
panded to produce the ellagitannin regioisomers, isorugosin B and
rugosin B. As discussed above, this class of ellagitannins has not
been previously synthesized because of difficulties inherent in the
construction of the valoneoyl group on the sugar moiety. However,
BnO
MeO
CO2Me
BnO
MeO
MeO
MeO
CO2Me
CO2Me
HO
MeO
MeO
MeO
CO2Me
CO2Me
OH
8
Cu
H2, Pd/C
O
O
neat
56%
MeOH
81%
Br
MeO
MeO
CO2Me
OMe
10
OMe
7
OMe
9
OMe
OMe
OMe
OMe
OMe
I
OMe
O
O
OMe
OMe
I
HOOC
OMe
O
CO2Me
O
CO2Me
[Pd]
6
MeO
MeO
MeO
MeO
MeO
MeO
O
EDC, DMAP, CH2Cl2
98%
O
CO2Me
CO2Me
OMe
4
OMe
5
Scheme 2. Attempt to construct the six-membered ring lactone 4.
Accordingly, the ester group was converted to a carbinol or
a protected carbinol, such as an acetoxymethyl or a siloxymethyl
group. Converting the ester to an unprotected carbinol did not
improve reactivity. In contrast, conversion to a protected carbinol
provided the desired results; the best yields were obtained with the
acetyl-protected carbinol. The synthesis of the six-membered lac-
tone 14 is summarized in Scheme 3. Two ester groups in 10 were
reduced with LiAlH4 and acetylated to yield the bis-acetoxymethyl
compound 11, which was debenzylated to form phenol 12. Phenol
12 was condensed with carboxylic acid 6 using the same conditions
as those in Scheme 2 to yield the coupling precursor 13. The
intramolecular biaryl coupling reaction of 13 with Pd(OAc)2, Ph3P,
and NaOAc produced the desired lactone 14 in good yield.
In the next stage, Bringmann’s lactone opening reaction was
applied to 14 to construct the axially chiral biaryl components
(Scheme 4). The asymmetric reduction of 14 with a boraneeCBS
reagent system17 succeeded in generating the optically active biaryl
compound 15 in an enantiomerically pure form. The phenolic hy-
droxy group was subsequently methylated, and successive reduction
the above strategy enabled a smooth conversion of the axially chiral
valoneoyl group into all-methylated versions of isorugosin B (2)
and rugosin B (3).
The syntheses of 2 and 3 were relatively simple, as illustrated in
Scheme 5. The most difficult step was the connection of the biaryl
unit to the sugar moiety. This requires that two ester groups be
formed in the final stage of the syntheses. In this context, the axially
chiral biaryl compound 18 was the rational intermediate for
regioselective esterification of glucose derivative 19.19 Although 18
can be obtained by a method analogous to that described above, the
three ester groups in the valoneoyl group must be distinguishable
from each other.
As depicted in Scheme 6, the synthesis started with the prepa-
ration of the biaryl ether by an Ullmann condensation between
(siloxymethyl)phenol 20, which was obtained by LiAlH4 reduction
and TBS protection of 8, and the bromide 9. Aldehyde 21 was iso-
lated in 9% yield along with many other undesired by-products. It is
likely that compound 20 underwent thermolysis of its silyl group,
with subsequent auto-oxidation, to afford the formyl compound 22

K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1963
BnO
MeO
MeO
MeO
CO2Me
CO2Me
BnO
OAc
HO
MeO
MeO
MeO
OAc
OAc
1) LiAlH4, THF
MeO
MeO
MeO
H2, Pd/C
93%
O
O
O
MeOH
89%
2) Ac2O, pyr.
89%
OAc
OMe
10
OMe
11
OMe
12
OMe
OMe
OMe
I
OMe
OMe
OMe
O
O
OMe
OMe
HOOC
OMe
I
O
Pd(OAc)2, PPh3
NaOAc
O
OAc
OAc
6
MeO
MeO
MeO
MeO
EDC, DMAP, CH2Cl2
quant.
DMA
64%
O
O
MeO
MeO
OAc
OAc
OMe
14
OMe
13
Scheme 3. Construction of six-membered ring lactone 14.
OMe
OMe
OMe
MeO
Ph
Ph
H
O
OH
OMe
BH3,
MeO
RO
O
N
B
O
OAc
OAc
Me
MeO
MeO
MeO
MeO
MeO
MeO
THF
84%, 99% ee
O
O
OAc
OAc
OMe
14
OMe
t
MeI, BuOK
THF, 51%
15 : R = H
16 : R = Me
OMe
OMe
MeO
MeO
OH
OH
MeO
MeO
MeO
MeO
CO2Me
CO2Me
1) Jones reagent
acetone
LiAlH4
2) H2O2, NaClO2
THF
quant.
MeO
MeO
MeO
MeO
MeO
MeO
NaH2PO4⋅2H2O
MeCN, H2O
3) TMSCHN2
MeOH
O
O
CO2Me
OH
37% (3 steps)
OMe
17
OMe
1
Scheme 4. Synthesis of (S)-1.
as a reactive species. Thus, it was considered that 22 would be
a suitable synthetic precursor for the formation of the biaryl ether.
Based on this, 22 was synthesized from 8 by LiAlH4 reduction and
Jones oxidation. The biaryl ether 21 was then obtained in good yield
from the reaction of 22 and 9. Reduction of the formyl group and
deprotection of the benzyl group provided the benzyl alcohol 23.
Protection of the benzylic hydroxy group of 23 using
a TBSCleimidazole system succeeded in providing the desired
phenol fragment 24. Phenol 24 was then coupled with carboxylic
acid 6 to afford the ester 25. Ester 25 was then subjected to the

1964
K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
OMe
OMe
MeO
OMe
O
MeO
MeO
MeO
MeO
MeO
MeO
CO O
CO O
MeO
MeO
CO2H
OTBS
CO2Me
O
HO
HO
O
O
O
OMe
G
+
O
G
MeO
MeO
MeO
G
MeO
MeO
MeO
O
OMe
O
O
G
MeO
MeO
CO O
CO O
O
O
CO2Me
CO2Me
19
O
OMe
G
OMe
OMe
OMe
Scheme 5. Synthetic outline of 2 and 3.
MeO
G
OMe
OMe
18
OMe
G :
3
2
O
BnO
MeO
MeO
MeO
CHO
HO
MeO
MeO
MeO
HO
MeO
MeO
MeO
OH
OTBS
1) NaBH4
MeOH
1) LiAlH4
BnO
MeO
CO2Me
BnO
MeO
9, Cu
TBSCl, imidazole
OTBS
THF, 85%
O
O
O
2) H2, Pd/C
MeOH
91% (2 steps)
neat, 200°C
9%
CH2Cl2
95%
2) TBSCl
imidazole
CH2Cl2, 80%
CO2Me
CO2Me
CO2Me
OH
OH
8
20
OMe
21
OMe
23
OMe
24
BnO
MeO
CHO
1) LiAlH4, THF
9, Cu
2) Jones ox.
44% (2 steps)
DMF, 200°C (temp. of bath)
73%
OH 22
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OTBS
OMe
Ph
MeO
OMe
MeO
MeO
RO
MeO
MeO
MeO
Ph
H
O
O
OH
BH3,
O
HOOC
OMe
MeO
MeO
CO2H
OTBS
OMe
N
Pd(OAc)2, Ph3P
B
1) PDC, CH2Cl2
I
I
O
O
NaOAc
6
Me
OTBS
83%, 96% ee
OTBS
MeO
MeO
MeO
MeO
MeO
MeO
THF
96%, 98% ee
EDC, DMAP, CH2Cl2
99%
DMA
53%
MeO
MeO
MeO
2) NaClO2
O
O
O
O
2-methyl-2-butene
NaH2PO4
CO2Me
CO2Me
CO2Me
CO2Me
t
THF/ BuOH/H2O
95%
OMe
OMe
18
OMe
26
OMe
25
t
MeI, BuOK, THF
80%, 97% ee
27 : R = H
28 : R = Me
Scheme 6. Synthesis of key intermediate 18.
intramolecular biaryl coupling reaction, using the same conditions
as those in the previous scheme, to afford lactone 26.
measurement of the optical rotation.20 Finally, a two-step oxidation
(PDC oxidation and Pinnick oxidation21) of (S)-28 resulted in the
optically active carboxylic acid (S)-18 as a key intermediate of the
synthesis.
With the mono carboxylic acid (S)-18 in hand, an 11-membered
ring system was formed via a double esterification reaction be-
tween 18 and a glucose derivative (Scheme 7). Glucose derivatives
The lactone opening reaction of 26 proceeded smoothly under
Bringmann’s conditions to generate the axially chiral biaryl com-
pound 27 in high enantiomeric excess, which was methylated to
afford the benzyl alcohol 28. The absolute configuration of the biaryl
moiety was confirmed by a one-pot transformation of 28 to 17, and
OMe
HO
OMe
OMe
1)
O
MeO
MeO
MeO
TBSO
O
G
O
OMe
O
MeO
MeO
CO
OH
O
MeO
MeO
CO
CO
O
O
MeO
MeO
CO
CO2H
29
G
O
O
O
O
O
O
TBSO
TBSO
O
O
O
EDC, DMAP
CH2Cl2
1) Dess-Martin
CH2Cl2, 99%
OMe
OMe
OMe
G
G
1) TBAF, THF
G
G
MeO
MeO
MeO
G
MeO
MeO
MeO
G
MeO
MeO
MeO
O
O
O
OMe
2) NaClO2
2) EDC, DMAP
CH2Cl2
32% (2 steps)
2) AcOH, THF/H2O
80% (2 steps)
CO2Me
CO2Me
CO2Me
MeO
2-methyl-2-butene
NaH2PO4
t
MeO
MeO
CO2H
THF/ BuOH/H2O
OMe
OMe
OMe
OMe
OMe
74%
OTBS
30
31
2
MeO
MeO
MeO
MOMO
HO
1)
O
O
O
G
OMe
O
CO2Me
O
OMe
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
32
G
EDC, DMAP
CH2Cl2, 64%
1) 6 N HCl aq.
MeOH/THF
1) PDC, CH2Cl2
98%
CO2Me
CO2Me
CO2Me
OMe
18
O
O
2) AcOH, THF/H2O
94%
2) EDC, DMAP
CH2Cl2
63% (2 steps)
2) NaClO2
OMOM
OMOM
OH
2-methyl-2-butene
MeO
MeO
MeO
MeO
CO2H
CO
MeO
MeO
CO
CO
O
O
O
O
G
O
O
G
O
O
NaH2PO4
O
O
CO
t
O
O
O
THF/ BuOH/H2O
OMe
OMe
OMe
OMe
OMe
OMe
G
G
G
100%
MeO
MeO
MeO
G
G =
OMe
OMe
OMe
O
33
34
3
Scheme 7. Synthesis of 2 and 3.

K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1965
29 and 32 were prepared from compound 19.22 The first attach-
ment of 18 to 29, followed by selective desilylation of the primary
alcohol, yielded the desired alcohol 30 as a single diastereoisomer,
which was then oxidized to the ring-closing precursor, carboxylic
acid 31. The final manipulation of 31 consisted of removal of the TBS
group with TBAF, and a subsequent intramolecular esterification
under typical conditions to afford all-methylated isorugosin B (2).
The moderate yield of this step may be due to the low reactivity of
the secondary hydroxy group of the sugar. While the NMR spec-
trum of synthetic 2 was identical to that of the authentic chart,
significant differences were observed regarding the sign of optical
rotation.23 This discrepancy was likely due to impurities in the
natural sample, as evidenced by unidentified peaks in the authentic
NMR chart.
and the resulting residue (31.2 g) was purified by silica gel column
chromatography (1:2; EtOAc/hexane) and recrystallization from
EtOAc/hexane, providing 21 (10.3 g, 73%) as pale yellow prisms: mp
108e109.5 ꢀC (EtOAc/hexane); IR (KBr) nmax 2950, 2840, 1725, 1700,
1590,1490,1460,1430,1415,1380,1350,1330,1230,1185,1125,1100,
1030, 990, 945, 840, 740, 700 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 3.74
(3H, s, OMe), 3.77 (3H, s, OMe), 3.94 (3H, s, OMe), 3.97 (3H, s, OMe),
4.10 (3H, s, OMe), 5.22 (2H, s, CH2), 6.65 (1H, d, J¼1.8 Hz, Ar-40 or
60-H), 7.20 (1H, d, J¼1.8 Hz, Ar-40 or 60-H), 7.31e7.51 (6H, m, C6H5, Ar-
6-H) 9.67 (1H, s, CHO); 13C NMR (75 MHz, CDCl3)
d 52.3, 56.3, 61.3,
61.3, 61.5, 71.2, 108.3, 108.9, 109.6, 119.3, 127.5, 128.2, 128.7, 131.4,
136.4, 142.1, 143.9, 147.0, 147.3, 150.5, 153.1, 153.2, 165.0, 190.9. Anal.
Calcd for C26H26O9: C, 64.72; H, 5.43. Found: C, 64.78; H, 5.21; FAB-
mass (positive ion mode) m/z: 482[M]þ, 483[MþH]þ
.
The current investigation was concluded with the synthesis of 3,
which is a regioisomer of 2. An esterification reaction between 18
and 32 with successive deprotection gave alcohol 33, which was
then subjected to a two-step oxidation to yield the carboxylic acid
34. Finally, deprotection of the MOM group on the sugar moiety
with aqueous HCl and successive esterification resulted in the
synthesis of all-methylated rugosin B (3). The NMR spectrum and
the optical rotation of synthetic 2 matched those of the reported
data.23
4.1.2. Methyl 2-(3-hydroxy-5-hydroxymethyl-2-methoxyphenoxy)-
3,4,5-trimethoxybenzoate (23). To a stirring solution of 21 (9.00 g,
18.7 mmol) in MeOH (200 mL), NaBH4 (1.42 g, 37.5 mmol) was
added and the resulting mixture was stirred at room temperature
under Ar atmosphere. After 30 min, the reaction mixture was
warmed to 40 ꢀC and stirred. After check of TLC, the reaction
mixture was quenched with 1 N HCl aq (100 mL) and evaporated to
remove most of MeOH. The resulting residue was poured into H2O
(50 mL) and extracted with EtOAc (150 mLꢁ3). The combined or-
ganic layer was washed with satd NaHCO3 aq (150 mL) and brine
(150 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated to afford alcohol (11.8 g) as colorless prisms, which was used
in the next reaction without further purification: mp 118e120 ꢀC
(EtOAc/hexane); IR (KBr) nmax 3500, 2960, 2360, 1700, 1600, 1430,
3. Conclusions
An efficient strategy for the synthesis of valoneoyl-containing
ellagitannins, which involved a Pd-catalyzed intramolecular biaryl
coupling reaction, Bringmann’s lactone opening reaction, and a two-
step ester formation with the sugar core, was demonstrated. This
process enabled syntheses of the valoneic acid derivative (1), and
all-methylated versions of isorugosin B (2) and rugosin B (3). Based
on these results, further syntheses of other natural ellagitannins,
including isorugosin B, rugosin B, and oenothein B are underway.
1350, 1240, 1220, 1130, 1100, 740 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
3.73 (3H, s, OMe), 3.78 (3H, s, OMe), 3.92 (3H, s, OMe), 3.96 (3H, s,
OMe), 4.00 (3H, s, OMe), 4.44 (2H, s, CH2OH), 5.16 (2H, s, PhCH2O),
6.09 (1H, d, J¼1.8 Hz, Ar-40 or 60-H), 6.68 (1H, d, J¼1.8 Hz, Ar-40 or
60-H), 7.28e7.49 (6H, m, C6H5, Ar-6-H); 13C NMR (75 MHz, CDCl3)
d
52.3, 56.2, 61.1, 61.3, 61.5, 65.0, 71.0,105.8,106.3,108.7,119.4,127.4,
4. Experimental section
4.1. General information
128.0, 128.6, 136.5, 137.1, 137.6, 142.7, 147.1, 147.2, 150.1, 152.6, 152.9,
165.5. Anal. Calcd for C26H28O9: C, 64.45; H, 5.83. Found: C, 64.37;
H, 5.74. Found: C, 69.74; H, 5.42; FAB-mass (positive ion mode) m/z:
484[M]þ, 485[MþH]þ. The above alcohol was dissolved in MeOH
(100 mL), 10% Pd/C (1.00 g) was added at room temperature. Under
H2 (1 atm) atmosphere, the mixture was stirred for 2 h, which was
filtrated and evaporated. The obtained colorless solid (8.16 g) was
recrystallized from EtOAc/hexane, providing 23 (6.72 g, 91%) as
a colorless solid: mp 141e143 ꢀC (EtOAc/hexane); IR (KBr) nmax
3480, 3160, 3000, 2960, 1720, 1600, 1460, 1430, 1410, 1360, 1220,
Melting points were measured using Yanagimoto micro melting
point hot-plate and are uncorrected. Optical rotations were de-
termined on a JASCO P-1020 or -1030 digital polarimeter. IR spectra
were recoded on a Jasco FTIR-350 spectrophotometer. NMR spectra
were taken with Varian Unity INOVA AS600 (600 MHz), Varian VXR-
500 (500 MHz), Mercury 300 (300 MHz) or JEOL
instrument. Chemical shifts are given in parts per millionwith TMS
a-400 (400 MHz)
d
1080, 1040, 995, 965, 800, 780 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
as an internal standard. Elemental analyses were performed with
Yanaco MT-5 or Elementar vario MICRO cube analyzer. FABMS was
obtained with a VG-70SE or JEOL JMS-AX505HAD instrument using
m-nitrobenzyl alcohol as the matrix. EIMS was obtained with JEOL
JMS-700 or JMS-GCmate II instrument. HPLC was carried out using
a Shimadzu LC-6A system, Shimadzu SPD-6A UV detector, Daicel
CHIRALPACKÒ AD or CHIRALCELÒ OD column. Silica gel column
chromatography was carried out using wakogelÒ C-200 (Wako) or
9385 Kieselgel 60 (Merck). TLC analysis was performed on Kieselgel
60 F254 (Merck) plates. Solvents were dried using standard
procedure.
d 3.73 (3H, s, OMe), 3.75 (3H, s, OMe), 3.93 (3H, s, OMe), 3.96 (3H, s,
OMe), 4.07 (3H, s, OMe), 4.41 (2H, s, CH2OH), 5.95 (1H, s, ArOH,
exchange with D2O), 5.98 (1H, d, J¼1.8 Hz, Ar-40 or 60-H), 6.60 (1H,
d, J¼1.8 Hz, Ar-40 or 60-H), 7.28 (1H, s, Ar-6-H); 13C NMR (75 MHz,
CDCl3)
d 52.4, 56.3, 61.3, 61.5, 64.9, 104.4, 107.5, 108.8, 119.5, 134.8,
137.0, 142.2, 147.1, 147.3, 149.7, 150.3, 151.9, 165.4. Anal. Calcd for
C19H22O9: C, 57.86; H, 5.62. Found: C, 57.81; H, 5.43; FAB-mass
(positive ion mode) m/z: 394[M]þ.
4.1.3. Methyl
2-(5-tert-butyldimethylsilyloxymethyl-3-hydroxy-2-
methoxyphenoxy)-3,4,5-trimethoxybenzoate (24). To a solution of
23 (4.50 g,11.4 mmol) in CH2Cl2 (150 mL), TBSCl (3.10 g, 20.6 mmol)
and imidazole (1.40 g, 20.6 mmol) were added at room tempera-
ture. After stirring for 10 min under Ar atmosphere, the mixture
was poured into H2O (100 mL) and extracted with CH2Cl2
(100 mLꢁ3). The combined organic layer was washed with brine
(100 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated, and the pale yellow residue (11.1 g) was purified by silica gel
column chromatography (1:2; EtOAc/hexane), providing 24 (5.49 g,
95%) as a colorless oil: IR (neat) nmax 3440, 2960, 2860, 2360, 1730,
4.1.1. Methyl 2-(3-benzyloxy-5-formyl-2-methoxyphenoxy)-3,4,5-tri-
methoxybenzoate (21). The mixture of 22 (7.50 g, 29.0 mmol), 9
(26.6 g, 87.2 mmol), and Cu (11.1 g, 175 mmol) in DMF (25 mL) was
heated at 200 ꢀC under Ar. After stirring for 1 h, the reaction mixture
was cooled to ambient temperature, diluted with EtOAc, and fil-
trated. The filtrate was poured into H2O (250 mL) and extracted with
EtOAc (250 mLꢁ3). The combined organic layer was washed with
brine, dried over MgSO4, and filtrated. The filtrate was evaporated

1966
K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1720, 1600, 1505, 1495, 1460, 1430, 1415, 1350, 1220, 1120, 1080,
methoxycarbonylphenoxy)-1,10-biphenyl (27). To a solution of (S)-
5,5-diphenyl-2-methyl-3,4-propano-1,3,2-oxazaborolidine (2.37 g,
8.55 mmol) in THF (50 mL), 1.06 M BH3$THF in THF solution
(10.8 mL, 11.4 mmol) was added at 0 ꢀC and the mixture was
warmed to room temperature. After stirring for 30 min under N2
atmosphere, a solution of 26 (2.00 g, 2.85 mmol) in THF (120 mL)
was dropwise added for 1 h at ꢂ40 ꢀC and the resulting mixture
was stirred for 15 h at the same temperature. The reaction mixture
was then quenched with H2O (50 mL), evaporated to remove most
of THF, and poured into H2O (50 mL). The aqueous solution was
acidified with 10% HCl aq (0.5 mL) and extracted with Et2O
(120 mLꢁ3). The combined organic layer was washed with brine
(100 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated and the pale yellow residue (5.08 g) was purified by silica gel
column chromatography (2:1; EtOAc/hexane), providing 27 (1.93 g,
1040, 990, 840, 780 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
ꢂ0.04 (6H, s,
SiMe2), 0.80 (9H, s, SitBu), 3.72 (3H, s, OMe), 3.74 (3H, s, OMe), 3.92
(3H, s, OMe), 3.95 (3H, s, OMe), 4.07 (3H, s, OMe), 4.48 (2H, s,
CH2OTBS), 5.85 (1H, s, ArOH, exchange with D2O), 5.96 (1H, d,
J¼1.8 Hz, Ar-40 or 60-H), 6.54 (1H, d, J¼1.8 Hz, Ar-40 or 60-H), 7.29
(1H, s, Ar-6-H); 13C NMR (75 MHz, CDCl3)
d
ꢂ5.3, 18.3, 25.9, 52.4,
56.4, 61.3, 61.4, 61.4, 64.4, 103.4, 106.0, 108.8, 119.6, 134.1, 137.5,
142.4, 147.3, 147.4, 149.5, 150.3, 151.8, 165.4. Anal. Calcd for
C25H36O9Si: C, 59.03; H, 7.13. Found: C, 58.73; H, 7.09; FAB-mass
(positive ion mode) m/z: 508[M]þ, 509[MþH]þ
.
4.1.4. 5-tert-Butyldimethylsilyloxymethyl-2-methoxy-3-(2,3,4-trime-
thoxy-6-methoxycarbonylphenoxy)-phenyl-2-iodo-3,4,5-trimethox-
ybenzoate (25). To a solution of 6 (4.38 g, 13.0 mmol) and 24
(5.49 g, 10.8 mmol) in CH2Cl2 (100 mL), EDC (3.10 g, 16.2 mmol) and
DMAP (0.396 g, 3.24 mmol) were added at room temperature. After
stirring for 3 h under Ar atmosphere, the reaction mixture was
poured into H2O (200 mL) and then extracted with CH2Cl2
(100 mLꢁ3). The combined organic layer was washed with brine
(100 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated to give the pale yellow residue (11.3 g), which was purified by
silica gel column chromatography (1:2; EtOAc/hexane), providing
25 (8.93 g, 100%) as a colorless amorphous foam: IR (CHCl3) nmax
3020, 2940, 2860, 1730, 1590, 1460, 1430, 1340, 1230, 1200, 1170,
96%, 98% ee) as a colorless solid: mp 77.9e80.9 ꢀC (Et2O/hexane);
18
[a
]
ꢂ2.4 (c 0.54, CHCl3); IR (CHCl3) nmax 3680, 3000, 2940, 2860,
D
1710,1595,1485,1460,1435,1420,1340,1235,1120,1090,1000, 840,
670 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
ꢂ0.19 (3H, s, SiMe), ꢂ0.19
(3H, s, SiMe), 0.68 (9H, s, SitBu), 3.56 (3H, s, OMe), 3.74 (3H, s, OMe),
3.76 (3H, s, OMe), 3.89 (3H, s, OMe), 3.92 (3H, s, OMe), 3.93 (3H, s,
OMe), 3.96 (3H, s, OMe), 4.07 (1H, d, B of AB, J¼13.2 Hz, CHAHB), 4.13
(3H, s, OMe), 4.21 (1H, d, A of AB, J¼13.2 Hz, CHAHB), 4.24 (2H, s,
CH2), 6.26 (1H, s, 5-H), 6.91 (1H, s, 50-H), 7.30 (1H, s, Phenoxy-5-H);
13C NMR (75 MHz, CDCl3)
d
ꢂ5.6, ꢂ5.5, 18.2, 25.8, 52.3, 56.0, 56.4,
1125, 1105, 1080, 1040, 1000, 840, 670 cmꢂ1
;
1H NMR (500 MHz,
60.9, 61.1, 61.3, 61.3, 61.5, 62.8, 63.8, 105.3, 108.6, 108.9, 114.1, 119.6,
120.6, 134.3, 135.9, 136.1, 142.0, 142.5, 146.7, 147.3, 147.4, 150.4, 151.3,
151.6, 153.4, 165.5. Anal. Calcd for C35H48O13Si: C, 59.64; H, 6.86.
Found: C, 59.64; H, 6.98; FAB-mass (positive ion mode) m/z: 704
[M]þ; HPLC conditions: Daicel CHIRALPACKÒ AD, iPrOH/hexane
1:15, 1.0 mL minꢂ1, 254 nm, tR (minor)¼24.7 min, tR (major)¼29.4 min.
CDCl3)
d
ꢂ0.02 (6H, s, SiMe2), 0.81 (9H, s, SitBu), 3.75 (3H, s, OMe),
3.78 (3H, s, OMe), 3.91 (3H, s, OMe), 3.93 (3H, s, OMe), 3.95 (3H, s,
OMe), 3.96 (6H, s, OMe), 4.04 (3H, s, OMe), 4.57 (2H, s, CH2OTBS),
6.39 (1H, d, J¼2.0 Hz, phenyl-6-H), 6.80 (1H, d, J¼2.5 Hz, phenyl-4-
H), 7.31 (1H, s, phenyl-50-H), 7.52 (1H, s, benzoate-6-H); 13C NMR
(75 MHz, CDCl3)
d
ꢂ5.3, 18.2, 25.9, 52.5, 56.4, 56.5, 61.0, 61.2, 61.3,
61.3, 61.5, 63.9, 84.9, 108.9, 109.6, 111.4, 113.0, 119.5, 129.9, 137.1,
139.4, 142.3, 144.1, 145.6, 147.2, 147.3, 150.4, 153.0, 153.5, 154.2,
164.6, 165.4; HRMS (FAB, positive ion mode) calculated for
C35H46O13SiI [MþH]þ: 829.1753; found: 829.1744 [MþH]þ.
4.1.7. (S)-6-tert-Butyldimethylsilyloxymethyl-60-hydroxymethyl-
2,20,3,3040-pentamethoxy-4-(2,3,4-trimethoxy-6-methox-
ycarbonylphenoxy)-1,10-biphenyl (28). To a solution of 27 (1.86 g,
t
2.64 mmol) in THF (60 mL), MeI (0.2 mL, 3.21 mmol) and BuOK
(0.360 g, 3.21 mmol) were added at 0 ꢀC. The resulting mixture was
warmed to room temperature and stirred for 48 h under N2 atmo-
sphere. The reaction mixture was poured into H2O (100 mL) and
extracted with Et2O (150 mLꢁ3). The combined organic layer was
washed with brine (50 mL), dried over MgSO4, and filtrated. The
filtrate was evaporated and the resulting residue (1.97 g) was puri-
4.1.5. 1-tert-Butyldimethylsilyloxymethyl-3-(2,3,4-trimethoxy-6-me-
thoxycarbonylphenoxy)-4,8,9,10-tetramethoxydibenzo [b,d] pyran-6-
one (26). To a stirring solution of 25 (8.47 g, 10.2 mmol) in DMA
(150 mL), NaOAc (1.68 g, 20.5 mmol), Pd(OAc)2 (572 mg, 2.55 mmol),
and PPh3 (1.34 g, 5.11 mmol) were added at room temperature. The
resulting mixture was heated at 120 ꢀC and stirred under Ar atmo-
sphere. After 80 min, the reaction mixture was cooled to room
temperature, diluted with EtOAc (300 mL), and filtrated to remove
solid material. The filtrate was poured into H2O (500 mL) and
extracted with EtOAc (300 mLꢁ3). The combined organic layer was
washed with brine (200 mL), dried over MgSO4, and filtrated. The
filtrate was evaporated and the resulting residue (15.2 g) was puri-
fied by silica gel column chromatography (1:2; EtOAc/hexane) and
recrystallization from EtOAc/hexane, providing 26 (3.77 g, 53%) as
colorless needles: mp 171e173 ꢀC (EtOAc/hexane); IR (KBr) nmax
2950, 2850, 1735, 1595, 1480, 1460, 1430, 1340, 1220, 1120, 1080,
fied by silica gel column chromatography (1:1; EtOAc/hexane),
18
providing 28 (1.52 g, 80%, 97% ee) as a pale yellow amorphous: [
a]
D
þ17.6 (c 0.53, CHCl3); IR (CHCl3) nmax 3020, 2940, 2860, 1710, 1595,
1480, 1460, 1430,1415, 1395, 1350,1320,1235,1120,1090,1000, 840,
670 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d
ꢂ0.19 (3H, s, SiMe), ꢂ0.18
(3H, s, SiMe), 0.68 (9H, s, SitBu), 3.66 (3H, s, OMe), 3.73 (3H, s, OMe),
3.74 (3H, s, OMe), 3.78 (3H, s, OMe), 3.86 (3H, s, OMe), 3.92 (3H, s,
OMe), 3.93 (3H, s, OMe), 3.96 (3H, s, OMe), 4.03 (1H, d, B of AB,
J¼13.5 Hz, CHAHBOTBS), 4.04 (3H, s, OMe), 4.15 (2H, s, ArCH2OH),
4.24 (1H, d, A of AB, J¼13.5 Hz, CHAHBOTBS), 6.48 (1H, s, Ar-5-H), 6.87
(1H, s, Ar-50-H), 7.30 (1H, s, phenoxy-5-H); 13C NMR (75 MHz, CDCl3)
1000, 840, 780 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d
ꢂ0.18 (6H, s,
d
ꢂ5.5, ꢂ5.5, 18.2, 25.8, 52.3, 56.0, 56.4, 60.7, 60.9, 61.1, 61.3, 61.3,
SiMe2), 0.70 (9H, s, SitBu), 3.49 (3H, s, OMe), 3.72 (3H, s, OMe), 3.80
(3H, s, OMe), 3.94 (3H, s, OMe), 3.98 (3H, s, OMe), 4.00 (3H, s, OMe),
4.05 (3H, s, OMe), 4.16 (3H, s, OMe), 4.60 (2H, s, CH2OTBS), 6.77 (1H, s,
Ar-2-H), 7.33 (1H, s, Ar-50-H), 7.69 (1H, s, Ar-7-H); 13C NMR (75 MHz,
62.6, 63.9, 108.4, 108.8, 108.9, 119.5, 121.0, 121.1, 135.7, 135.8, 140.7,
141.5,143.0, 147.2,147.4,150.2, 151.0, 151.2,152.7, 153.4, 165.6; HRMS
(EI) calculated for C36H50O13Si [M]þ: 718.3021; found: 718.2998
[M]þ; HPLC conditions: Daicel CHIRALCELÒ OD, iPrOH/hexane 1:15,
0.5 mL minꢂ1, 254 nm, tR(minor)¼35.6 min, tR (major)¼44.3 min.
CDCl3)
d
ꢂ5.5, 18.2, 25.8, 52.3, 56.4, 56.5, 61.3, 61.4, 61.5, 61.5, 61.9,
64.0, 108.0, 109.0, 109.6, 110.2, 118.1, 119.4, 123.3, 134.7, 135.0, 142.3,
144.2, 147.2, 147.4, 148.4, 149.5, 150.5, 152.3, 153.1, 161.0, 165.2. Anal.
Calcd for C35H44O13Si: C, 59.98; H, 6.33. Found: C, 59.74; H, 6.31; FAB-
4.1.8. (S)-60-tert-Butyldimethylsilyloxymethyl-2,20,3,304-pentam-
ethoxy-40-(2,3,4-trimethoxy-6-methoxycarbonylphenoxy)-1,10-bi-
phenyl-6-carboxylic acid (18). To a stirring suspension of PDC
(1.46 g, 3.88 mmol) in CH2Cl2 (10 mL), a solution of 28 (1.40 g,
1.95 mmol) in CH2Cl2 (30 mL) was added at 0 ꢀC. After stirring for
25 h at room temperature, the reaction mixture was filtrated with
mass (positive ion mode) m/z: 700[M]þ, 701[MþH]þ
.
4.1.6. (S)-6-tert-Butyldimethylsilyloxymethyl-2-hydroxy-60-hydrox-
ymethyl-20,3,3040-tetramethoxy-4-(2,3,4-trimethoxy-6-

K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1967
Celite and the filtrate was evaporated. The resulting residue (1.68 g)
was purified by silica gel column chromatography (1:2; EtOAc/
hexane), providing aldehyde (1.16 g, 83%, 96% ee) as a colorless
(2:1; EtOAc/hexane), providing colorless amorphous 30 (1.05 g,
17
80%) as a single diastereoisomer: [
(CHCl3) nmax 2940, 2360, 1720, 1590, 1460, 1420, 1340, 1230, 1130,
1085, 840, 670 cmꢂ1 1H NMR (400 MHz, CDCl3)
a]
þ88.5 (c 0.57, CHCl3); IR
D
15
amorphous: [
a]
þ3.5 (c 0.46, CHCl3); IR (CHCl3) nmax 3010, 2940,
;
d
ꢂ0.09 (3H, s,
D
2860, 1710, 1680, 1590, 1480, 1460, 1430, 1415, 1350, 1320, 1230,
SiMe), 0.08 (3H, s, SiMe), 0.77 (9H, s, SitBu), 2.64 (1H, t, J¼6.0 Hz,
CH2OH, exchange with D2O), 3.39 (3H, s, OMe), 3.58 (3H, s, OMe),
3.754 (3H, s, OMe), 3.75 (3H, s, OMe), 3.76 (6H, s, OMe), 3.83 (9H, s,
OMe), 3.85 (6H, s, OMe), 3.85 (3H, s, OMe), 3.92 (3H, s, OMe), 3.93
(3H, s, OMe), 3.94 (3H, s, OMe), 3.95 (3H, s, OMe), 3.99e4.14 (3H,
m), 4.00 (3H, s, OMe), 4.64 (1H, dd, A of ABX, J¼1.2, 11.6 Hz, 6-H),
4.90 (1H, dd, J¼3.6, 10.0 Hz, 2-H), 5.08 (1H, d, J¼3.6 Hz, 1-H), 5.82
(1H, dd, J¼8.4, 10.0 Hz, 3-H), 6.48 (1H, s, Valoneoyl-H), 7.17 (2H, s,
Galloyl-H), 7.18 (2H, s, Galloyl-H), 7.264 (1H, s, Valoneoyl-H), 7.35
1120, 1090, 1000, 840, 670 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d
ꢂ0.213 (3H, s, SiMe), ꢂ0.209 (3H, s, SiMe), 0.67 (9H, s, SitBu), 3.62
(3H, s, OMe), 3.73 (3H, s, OMe), 3.75 (3H, s, OMe), 3.79 (3H, s, OMe),
3.92 (3H, s, OMe), 3.96 (3H, s, OMe), 3.97 (3H, s, OMe), 3.98 (3H, s,
OMe), 4.04 (3H, s, OMe), 4.07 (1H, d, B of AB, J¼14.0 Hz, CHAH-
BOTBS), 4.21 (1H, d, A of AB, J¼14.0 Hz, CHAHBOTBS), 6.51 (1H, s, Ar-
5-H), 7.30 (1H, s, ArH), 7.35 (1H, s, ArH), 9.55 (1H, s, CHO); 13C NMR
(75 MHz, CDCl3)
d
ꢂ5.6, ꢂ5.6, 18.1, 25.8, 52.3, 56.2, 56.4, 60.8, 61.2,
61.3, 61.4, 62.5, 105.1, 107.8, 108.9, 117.2, 119.5, 128.2, 129.8, 136.2,
140.3, 142.8, 147.3, 147.4, 147.8, 150.3, 151.3, 151.7, 153.4, 153.4, 165.5,
191.3. Anal. Calcd for C36H48O13Si: C, 60.32; H, 6.75. Found: C, 60.22;
H, 7.05; FAB-mass (positive ion mode) m/z: 716 [M]þ, 717 [MþH]þ;
HPLC conditions: Daicel CHIRALPACKÒ AD, iPrOH/hexane 1:30,
0.5 mL minꢂ1, 254 nm, tR (minor)¼18.6 min, tR (major)¼21.5 min. The
above aldehyde (1.10 g, 1.50 mmol) was dissolved in THF (10 mL)
(1H, s, Valoneoyl-H); 13C NMR (100 MHz, CDCl3)
d
ꢂ4.5, ꢂ4.0, 17.9,
25.6, 52.2, 55.4, 56.1, 56.2, 56.3, 56.3, 60.8, 60.9, 60.9, 60.9, 61.0, 61.1,
61.2, 61.3, 63.5, 63.9, 69.9, 70.1, 72.9, 73.5, 96.7, 107.0, 107.2, 108.8,
109.3, 110.9, 119.5, 123.3, 124.1, 124.9, 125.9, 126.1, 134.9, 141.7, 142.6,
142.6, 143.1, 146.2, 147.3, 147.4, 150.2, 151.1, 152.0, 152.6, 152.9, 153.0,
153.1, 165.8, 165.8, 165.9, 166.6; HRMS (FAB, positive ion mode)
calculated for C63H81O27Si [MþH]þ: 1297.4735; found: 1297.4753
[MþH]þ.
t
and BuOH (10 mL), and 2-methyl-2-butene (1.30 mL, 12.2 mmol)
was added. The mixture was stirred at room temperature, and
a solution of 80% NaClO2 (0.520 g, 4.60 mmol) and NaH2PO4$2H2O
(1.20 g, 7.69 mmol) in H2O (10 mL) was dropwise added at room
temperature. After stirring for 3 h, the reaction mixture was poured
into H2O (10 mL) and extracted with Et2O (50 mLꢁ3). The com-
bined organic layer was washed with brine (30 mL), dried over
MgSO4, and filtrated. The filtrate was evaporated and the resulting
residue (1.54 g) was purified by silica gel column chromatography
(1:1; EtOAc/hexane), providing 18 (1.07 g, 95%) as a colorless
4.1.10. Methyl
4-O-tert-butyldimethylsilyl-6-O-[(S)-2-{6-carboxy-
2,3-dimethoxy-4-(2,3,4-trimethoxy-6-methoxycarbonylphenoxy)-
phenyl}-3,4,5-trimethoxybenzoyl]-2,3-di-O-(3,4,5-trimethoxy-
benzoyl)-a-D-glucopyranoside (31). To a solution of 30 (873 mg,
0.673 mmol) in CH2Cl2 (25 mL), DesseMartin periodinane (570 mg,
1.34 mmol) was added at room temperature. After the reaction
mixture was stirred for 3 h, it was quenched with 10% Na2S2O3 aq
(10 mL), poured into H2O (40 mL), and extracted with CH2Cl2
(25 mLꢁ3). The combined organic layer was washed with brine
(25 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated and the colorless residue (978 mg) was purified by silica gel
column chromatography (2:1; EtOAc/hexane), providing aldehyde
amorphous: [
a
]
D
15 þ16.0 (c 0.57, CHCl3); IR (CHCl3) nmax 3010, 2940,
2860, 1720, 1595, 1480, 1460, 1430, 1420, 1400, 1350, 1320, 1230,
1120, 1085, 1035, 1000, 840, 670 cmꢂ1 1H NMR (500 MHz, CDCl3)
;
d
ꢂ0.17 (3H, s, SiMe), ꢂ0.14 (3H, s, SiMe), 0.68 (9H, s, SitBu), 3.59 (3H,
s, OMe), 3.75 (3H, s, OMe), 3.75 (3H, s, OMe), 3.77 (3H, s, OMe), 3.93
(3H, s, OMe), 3.93 (3H, s, OMe), 3.94 (3H, s, OMe), 3.96 (3H, s, OMe),
4.00 (3H, s, OMe), 4.11 (1H, d, B of AB, J¼11.5 Hz, CHAHBOTBS), 4.33
(1H, d, A of AB, J¼11.5 Hz, CHAHBOTBS), 6.33 (1H, s, Ar-50-H), 7.21
(865 mg, 99%) as a colorless amorphous: [
a
]
D
18 þ52.9 (c 0.66, CHCl3);
IR (CHCl3) nmax 3020, 2940, 1720, 1685, 1590, 1460, 1420, 1340, 1230,
1175, 1130, 1090, 1035, 1000, 840, 670 cmꢂ1 1H NMR (400 MHz,
;
CDCl3)
d
ꢂ0.11 (3H, s, SiMe), 0.02 (3H, s, SiMe), 0.75 (9H, s, SitBu),
(1H, s, ArH), 7.29 (1H, s, ArH); 13C NMR (75 MHz, CDCl3)
d
ꢂ5.7,
3.37 (3H, s, OMe), 3.58 (3H, s, OMe), 3.74 (6H, s, OMe), 3.75 (3H, s,
OMe), 3.827 (6H, s, OMe), 3.833 (3H, s, OMe), 3.85 (9H, s, OMe), 3.93
(3H, s, OMe), 3.948 (3H, s, OMe), 3.954 (3H, s, OMe), 3.96 (3H, s,
OMe), 4.12 (3H, s, OMe), 4.58 (1H, dd, A of ABX, J¼1.6, 11.6 Hz, 6-H),
4.92 (1H, dd, J¼3.6, 10.4 Hz, 2-H), 5.11 (1H, d, J¼3.6 Hz, 1-H), 5.82
(1H, dd, J¼8.4, 10.4 Hz, 3-H), 6.93 (1H, s, Valoneoyl-H), 7.17 (2H, s,
Galloyl-H), 7.19 (2H, s, Galloyl-H), 7.29 (1H, s, Valoneoyl-H), 7.46
(1H, s, Valoneoyl-H), 9.46 (1H, s, CHO), glu-4-, 5-, and 60-H over-
ꢂ5.6, 18.2, 25.8, 52.3, 56.2, 56.3, 60.7, 61.0, 61.0, 61.0, 61.2, 61.3, 63.8,
108.6, 108.8, 109.5, 119.6, 121.8, 124.2, 127.0, 134.0, 141.0, 143.0,
145.9, 147.3, 147.4, 150.2, 151.3, 151.4, 152.7, 152.8, 165.8, 170.6;
HRMS (EI) calculated for C36H48O14Si [M]þ: 732.2813; found:
732.2839 [M]þ.
4.1.9. Methyl
4-O-tert-butyldimethylsilyl-6-O-[(S)-2-{6-hydrox-
ymethyl-2,3-dimethoxy-4-(2,3,4-trimethoxy-6-methoxy-
carbonylphenoxy)-phenyl}-3,4,5-trimethoxybenzoyl]-2,3-di-O-(3,4,5-
trimethoxybenzoyl)-a-D-glucopyranoside (30). To a solution of 18
lapped with OMe signals; 13C NMR (100 MHz, CDCl3)
d
ꢂ4.5, ꢂ4.0,
17.9, 25.6, 52.3, 55.4, 56.2, 56.3, 56.3, 56.4, 60.7, 61.0, 61.0, 61.0, 61.2,
61.2, 61.2, 61.4, 63.6, 70.0, 70.1, 73.0, 73.6, 96.7, 107.0, 107.2, 108.5,
109.1, 109.5, 119.4, 123.4, 124.2, 124.9, 126.0, 129.4, 129.6, 142.6,
142.6, 146.1, 147.2, 147.5, 147.5, 150.6, 151.5, 152.4, 153.1, 165.3, 165.5,
165.8, 165.9, 190.5.; FAB-mass (positive ion mode) m/z: 1295
[MþH]þ. To a solution of the above aldehyde (256 mg, 0.198 mmol)
in THF (4 mL) and tBuOH (4 mL), 2-methyl-2-butene (0.166 mL,
1.58 mmol) was added at room temperature. A solution of 80%
NaClO2 (67.2 mg, 0.594 mmol) and NaH2PO4$2H2O (155 mg,
0.994 mmol) in H2O (2 mL) was dropwise added to the mixture.
After stirring for 12 h, the reaction mixture was acidified with 10%
HCl aq (1 mL) and extracted with Et2O (20 mLꢁ3). The combined
organic layer was washed with brine (10 mL), dried over MgSO4,
and filtrated. The filtrate was evaporated and the yellow residue
(283 mg) was purified by silica gel column chromatography
(1:14:28; EtOH/EtOAc/CHCl3), providing 31 (193 mg, 74%) as a col-
(742 mg, 1.01 mmol) and 29 (845 mg, 1.21 mmol) in CH2Cl2 (12 mL),
EDC (350 mg, 1.83 mmol) and DMAP (50.0 mg, 0.410 mmol) were
added at room temperature. After stirring for 24 h under N2 at-
mosphere, the reaction mixture was poured into H2O (25 mL) and
then extracted with CH2Cl2 (25 mLꢁ3). The combined organic layer
was washed with brine (25 mL), dried over MgSO4, and filtrated.
The filtrate was evaporated and the colorless residue (1.67 g) was
subjected to silica gel column chromatography (1:1; EtOAc/hex-
ane), providing a mixture (1.47 g) of ester product and 29 as a col-
orless amorphous foam. The obtained mixture was directly
dissolved in THF (7 mL) and H2O (14 mL), and then AcOH (42 mL)
was added to the solution which was stirred at room temperature.
After 9 h, the reaction mixture was extracted with Et2O (100 mLꢁ3)
and the combined organic layer was washed with satd NaHCO3 aq
(80 mLꢁ3), H2O (80 mL), and brine (80 mL). The organic solution
was dried over MgSO4, filtrated, and evaporated. The resulting
residue (1.37 g) was purified by silica gel column chromatography
orless amorphous: [
a
]
19 þ65.1 (c 0.80, CHCl3); IR (CHCl3) nmax 3020,
D
2940, 2360, 1720, 1590, 1460, 1420, 1340, 1230, 1130, 1085, 675,
665 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
ꢂ0.10 (3H, s, SiMe), 0.06

1968
K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
(3H, s, SiMe), 0.76 (9H, s, SitBu), 3.38 (3H, s, OMe), 3.57 (3H, s, OMe),
3.68 (3H, s, OMe), 3.74 (3H, s, OMe), 3.76 (3H, s, OMe), 3.83 (6H, s,
OMe), 3.84 (3H, s, OMe), 3.858 (6H, s, OMe), 3.862 (3H, s, OMe), 3.88
(3H, s, OMe), 3.93 (6H, s, OMe), 3.95 (3H, s, OMe), 4.06 (3H, s, OMe),
4.10 (1H, dd, B of ABX, J¼5.2, 11.6 Hz, 6-H), 4.63 (1H, dd, A of ABX,
J¼1.2, 11.6 Hz, 6-H), 4.91 (1H, dd, J¼3.6, 10.4 Hz, 2-H), 5.09 (1H, d,
J¼3.6 Hz, 1-H), 5.82 (1H, dd, J¼8.4, 10.4 Hz, 3-H), 6.98 (1H, s, Valo-
neoyl-H), 7.17 (2H, s, Galloyl-H), 7.19 (2H, s, Galloyl-H), 7.27 (1H, s,
Valoneoyl-H), 7.36 (1H, s, Valoneoyl-H), glu-4- and 5-H overlapped
evaporated and the pale yellow residue (2.01 g) was purified by
silica gel column chromatography (1:1; EtOAc/hexane), providing
25
ester (1.16 g, 64%) as a colorless amorphous: [
a
]
D
ꢂ1.0 (c 0.63,
CHCl3); IR (CHCl3) nmax 3030, 3010, 2940, 2840, 1725, 1590, 1505,
1460, 1420, 1340, 1235, 1175, 1130, 1085, 1035, 1000, 920, 860,
670 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
ꢂ0.19, (3H, s, SiMe), ꢂ0.10
(3H, s, SiMe), 0.68 (9H, s, SitBu), 3.09 (1H, dd, B of ABX, J¼3.2,
11.6 Hz, 6-H), 3.29 (3H, s, OMe), 3.39 (3H, s, OMe), 3.51 (3H, s, OMe),
3.564 (3H, s, OMe), 3.572 (1H, dd, A of ABX, J¼2.0,11.6 Hz, 6-H), 3.68
(3H, s, OMe), 3.73 (3H, s, OMe), 3.80 (3H, s, OMe), 3.84 (3H, s, OMe),
3.85 (3H, s, OMe), 3.86 (12H, s, OMe), 3.88 (3H, s, OMe), 3.91 (3H, s,
OMe), 3.94 (3H, s, OMe), 4.01 (3H, s, OMe), 4.06 (1H, d, B of AB,
J¼14.0 Hz, CHAHB), 4.19 (1H, d, A of AB, J¼14.0 Hz, CHAHB), 4.54 (1H,
d, B of AB, J¼6.8 Hz, CHAHB), 4.60 (1H, d, A of AB, J¼6.8 Hz, CHAHB),
5.03 (1H, dd, J¼3.6, 10.0 Hz, 2-H), 5.20 (1H, d, J¼3.6 Hz, 1-H), 5.54
(1H, t, J¼10.0 Hz, 3 or 4-H), 5.77 (1H, t, J¼10.0 Hz, 3 or 4-H), 6.50
(1H, s, Valoneoyl-H), 6.97 (1H, s, Valoneoyl-H), 7.16 (2H, s, Galloyl-
H), 7.23 (2H, s, Galloyl-H), 7.28 (1H, s, Valoneoyl-H), glu-5-H over-
with OMe signals; 13C NMR (100 MHz, CDCl3)
d
ꢂ4.5, ꢂ4.0, 18.0,
25.6, 52.3, 55.3, 55.9, 56.2, 56.3, 56.3, 60.6, 60.8, 60.9, 61.0, 61.0,
61.0, 61.2, 61.3, 63.4, 70.0, 70.2, 73.0, 73.6, 96.7, 107.1, 107.2, 108.9,
108.9, 112.7, 119.4, 124.2, 124.5, 124.6, 125.0, 127.1, 127.1, 142.6, 142.6,
142.7, 146.0, 146.2, 147.2, 147.4, 150.4, 151.5, 151.7, 152.0, 152.3, 153.1,
165.7, 165.8, 165.9, 166.0, 170.1; HRMS (FAB, negative ion mode)
calculated for C63H77O28Si [MꢂH]ꢂ: 1309.4371; found: 1309.4405
[MꢂH]ꢂ.
4.1.11. All-methylated isorugosin B (hexadecamethyl derivative of
lapped with OMe signals; 13C NMR (100 MHz, CDCl3)
d
ꢂ5.7, 18.0,
isorugosin B) (2). To a solution of 31 (55.6 mg, 42.4
mmol) in THF
25.7, 52.2, 55.4, 55.6, 55.7, 56.2, 56.3, 56.3, 60.5, 60.7, 60.9, 61.0, 61.0,
61.0, 61.2, 61.4, 62.1, 64.9, 68.4, 68.4, 71.5, 72.7, 97.0, 97.1, 107.0,
107.0,107.2,108.9, 109.3, 119.7,121.1, 124.3,124.5, 124.5,125.6, 136.0,
140.1, 142.5, 142.6, 143.2, 146.0, 147.4, 147.5, 150.3, 151.0, 151.6, 152.5,
152.9, 153.1,153.1, 165.4, 165.6,165.7,165.8; HRMS (FAB, positive ion
mode) calculated for C65H85O28Si [MþH]þ: 1341.4997; found:
1341.5002 [MþH]þ. To a solution of the above ester (1.00 g,
0.745 mmol) in THF (10 mL) and H2O (20 mL), AcOH (60 mL) was
added and stirred at room temperature. After 8 h, the reaction
mixture was quenched with satd NaHCO3 aq (300 mL) and
extracted with Et2O (250 mLꢁ3). The combined organic layer was
washed with satd NaHCO3 aq (150 mLꢁ3), H2O (200 mL), and brine
(200 mL) and then the resulting organic solution was dried over
MgSO4, filtrated, and evaporated. The yellow residue (941 mg) was
purified by silica gel column chromatography (2:1; EtOAc/hexane),
(4 mL), TBAF (85.0 L, 85.0 mol) was added at room temperature.
m
m
After stirring for 30 min under N2 atmosphere, the reaction mixture
was poured into H2O (10 mL), acidified with 10% HCl aq (1 mL), and
extracted with Et2O (15 mLꢁ3). The combined organic layer was
washed with brine (10 mL), dried over MgSO4, and filtrated. The
filtrate was evaporated to afford desilylated product (41.1 mg) as
a colorless amorphous, which was used in the next reaction with-
out further purification. The obtained material was dissolved in
CH2Cl2 (42 mL), and then EDC (81.3 mg, 424
mmol) and DMAP
(25.9 mg, 212 mol) were added to the solution at room tempera-
m
ture. The reaction mixture was stirred for 42 h under N2 atmo-
sphere, it was poured into H2O (40 mL) and extracted with Et2O
(40 mLꢁ3). The combined organic layer was washed with brine
(40 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated and the resulting residue (87.3 mg) was purified by silica gel
column chromatography (1:7; EtOAc/CH2Cl2), providing all-meth-
ylated isorugosin B (2) (15.8 mg, 32%) as a colorless amorphous:
providing colorless amorphous 33 (862 mg, 94%) as a single di-
25
astereoisomer: [
a
]
D
þ9.9 (c 0.60, CHCl3); IR (CHCl3) nmax 3520,
3030, 3010, 2940, 2840, 1720, 1590, 1505, 1460, 1420, 1340, 1230,
1175, 1130, 1085, 1035, 1000, 920, 865, 670 cmꢂ1 1H NMR
(400 MHz, CDCl3)
2.85 (1H, t, J¼6.4 Hz, CH2OH), 3.28 (3H, s, OMe),
[
a]
25 þ28.0 (c 1.52, acetone); 1H NMR (400 MHz, acetone-d6)
d
3.44
;
D
(3H, s, OMe), 3.64 (3H, s, OMe), 3.66 (3H, s, OMe), 3.69 (3H, s, OMe),
3.70 (3H, s, OMe), 3.74 (3H, s, OMe), 3.75 (6H, s, OMe), 3.76 (3H, s,
OMe), 3.85 (6H, s, OMe), 3.89 (3H, s, OMe), 3.90 (3H, s, OMe), 3.94
(3H, s, OMe), 3.95 (1H, dd, B of ABX, J¼1.2, 13.2 Hz, 6-H), 3.98 (3H, s,
OMe), 4.00 (3H, s, OMe), 4.44 (1H, ddd, J¼1.2, 6.4, 10.0 Hz, 5-H), 5.15
(1H, dd, J¼4.0, 10.0 Hz, 2-H), 5.17 (1H, t, J¼10.0 Hz, 4-H), 5.25 (1H,
dd, A of ABX, J¼6.4, 13.2 Hz, 6-H), 5.26 (1H, d, J¼4.0 Hz, 1-H), 5.67
(1H, t, J¼10.0 Hz, 3-H), 6.34 (1H, s, Valoneoyl-H), 6.98 (1H, s,
Valoneoyl-H), 7.13 (2H, s, Galloyl-H), 7.23 (2H, s, Galloyl-H), 7.29
d
3.45 (3H, s, OMe), 3.51 (1H, dd, B of ABX, J¼4.0, 11.6 Hz, 6-H), 3.54
(3H, s, OMe), 3.55 (3H, s, OMe), 3.64 (1H, dd, A of ABX, J¼2.4,
11.6 Hz, 6-H), 3.75 (3H, s, OMe), 3.82 (9H, s, OMe), 3.84 (3H, s, OMe),
3.847 (6H, s, OMe), 3.854 (6H, s, OMe), 3.89 (3H, s, OMe), 3.93 (3H, s,
OMe), 3.96 (3H, s, OMe), 4.01 (3H, s, OMe), 4.55 (1H, d, B of AB,
J¼6.8 Hz, OCHAHBOMe), 4.61 (1H, d, A of AB, J¼6.8 Hz, OCHAH-
BOMe), 5.07 (1H, dd, J¼3.2, 10.0 Hz, 2-H), 5.24 (1H, d, J¼3.2 Hz, 1-H),
5.44 (1H, t, J¼10.0 Hz, 3 or 4-H), 5.79 (1H, t, J¼10.0 Hz, 3 or 4-H),
6.49 (1H, s, Valoneoyl-H), 7.11 (2H, s, Galloyl-H), 7.19 (2H, s, Galloyl-
H), 7.23 (1H, s, Valoneoyl-H), 7.27 (1H, s, Valoneoyl-H), glu-5-H and
CH2OH overlapped with OMe signals; 13C NMR (100 MHz, CDCl3)
(1H, s, Valoneoyl-H); 13C NMR (100 MHz, acetone-d6)
d 52.4, 55.9,
56.4, 56.5, 56.5, 56.8, 60.6, 60.7, 60.9, 61.1, 61.1, 61.2, 61.3, 61.6, 64.0,
67.5, 71.0, 72.2, 73.6, 98.4, 107.0, 108.0, 108.1, 109.1, 109.7, 120.5,
123.0, 124.1, 125.0, 125.1, 128.9, 129.9, 142.6, 143.8, 144.0, 145.1,
145.2, 148.0, 148.2, 151.7, 153.5, 153.6, 153.9, 154.2, 154.3, 154.3,
165.8, 165.9, 166.3, 167.6, 168.2; HRMS (FAB, negative ion mode)
calculated for C56H59O27 [MꢂCH3]ꢂ: 1163.3244; found: 1163.3221
[MꢂCH3]ꢂ.
d
52.1, 55.6, 55.6, 56.0, 56.2, 56.2, 56.3, 60.4, 60.6, 60.9, 60.9, 61.0,
61.2, 61.4, 63.0, 65.4, 68.5, 68.6, 71.1, 72.5, 96.8, 97.0, 107.0, 107.2,
108.8, 108.9, 109.9, 119.6, 123.0, 124.0, 124.0, 124.7, 125.3, 134.6,
141.0, 142.7, 142.8, 143.0, 146.2, 147.3, 147.5, 150.2, 151.3, 151.6, 152.5,
152.8, 153.1, 165.2, 165.6, 165.8, 166.1; HRMS (FAB, positive ion
mode) calculated for C59H71O28 [MþH]þ: 1227.4132; found:
1227.4144 [MþH]þ.
4.1.12. Methyl 4-O-[(S)-2{6-hydroxymethyl-2,3-dimethoxy-4-(2,3,4-
trimethoxy-6-methoxycarbonylphenoxy)-phenyl}-3,4,5-trimethox-
ybenzoyl]-6-O-methoxymethyl-2,3-di-O-(3,4,5-trimethoxybenzoyl)-
4.1.13. Methyl 4-O-[(S)-2-{6-carboxy-2,3-dimethoxy-4-(2,3,4-trime-
thoxy-6-methoxycarbonylphenoxy)-phenyl}-3,4,5-trimethoxy-
a-D-glucopyranoside (33). To a solution of 18 (983 mg, 1.34 mmol)
and 32 (1.01 g, 1.61 mmol) in CH2Cl2 (20 mL), EDC (462 mg,
2.41 mmol) and DMAP (65.5 mg, 0.536 mmol) were added at room
temperature. After stirring for 24 h under N2 atmosphere, the re-
action mixture was poured into H2O (100 mL) and then extracted
with CH2Cl2 (50 mLꢁ3). The combined organic layer was washed
with brine (50 mL), dried over MgSO4, and filtrated. The filtrate was
benzoyl]-6-O-methoxymethyl-2,3-di-O-(3,4,5-trimethoxybenzoyl)-a-
D-glucopyranoside (34). To a stirring suspension of PDC (918 mg,
2.44 mmol) in CH2Cl2 (50 mL),
a solution of 33 (749 mg,
0.610 mmol) in CH2Cl2 (100 mL) was added at 0 ꢀC. After stirring for
21 h at room temperature, the reaction mixture was filtrated with
Celite and the filtrate was evaporated. The resulting residue

K. Shioe et al. / Tetrahedron 67 (2011) 1960e1970
1969
(778 mg) was purified by silica gel column chromatography (2:1;
temperature. The reaction mixture was stirred for 2.5 day under N2
atmosphere, it was poured into H2O (80 mL) and extracted with
CH2Cl2 (100 mLꢁ3). The combined organic layer was washed with
brine (50 mL), dried over MgSO4, and filtrated. The filtrate was
evaporated and the resulting residue (441 mg) was purified by
silica gel column chromatography (1:1; EtOAc/hexane), providing
all-methylated rugosin B (3) (89.9 mg, 63%) as a colorless amor-
EtOAc/hexane), providing aldehyde (731 mg, 98%) as a colorless
amorphous: [
a
]
25 þ24.4 (c 0.59, CHCl3); IR (CHCl3) nmax 3030, 3010,
D
2940, 2840, 1730, 1690, 1590, 1505, 1460, 1420, 1340, 1230, 1175,
1130, 1090, 1035, 1000, 920, 860, 670 cmꢂ1
;
1H NMR (400 MHz,
CDCl3)
d
3.21 (1H, dd, B of ABX, J¼4.0, 11.6 Hz, 6-H), 3.27 (3H, s,
OMe), 3.42 (3H, s, OMe), 3.50 (3H, s, OMe), 3.54 (3H, s, OMe), 3.56
(1H, dd, A of ABX, J¼2.4, 11.6 Hz, 6-H), 3.75 (3H, s, OMe), 3.78 (3H, s,
OMe), 3.81 (3H, s, OMe), 3.83 (6H, s, OMe), 3.84 (3H, s, OMe), 3.85
(9H, s, OMe), 3.90 (3H, s, OMe), 3.94 (3H, s, OMe), 3.97(3H, s, OMe),
4.10 (3H, s, OMe), 4.48 (1H, d, B of AB, J¼6.8 Hz, OCHAHBOMe), 4.56
(1H, d, A of AB, J¼6.8 Hz, OCHAHBOMe), 5.07 (1H, dd, J¼3.6, 10.0 Hz,
2-H), 5.20 (1H, d, J¼3.6 Hz, 1-H), 5.44 (1H, t, J¼10.0 Hz, 3 or 4-H),
5.81 (1H, t, J¼10.0 Hz, 3 or 4-H), 6.89 (1H, s, Valoneoyl-H), 7.12 (2H,
s, Galloyl-H), 7.13 (1H, s, Valoneoyl-H), 7.20 (2H, s, Galloyl-H), 7.30
(1H, s, Valoneoyl-H), 9.42 (1H, s, CHO), glu-5-H was hidden by OMe
phous: [a]
25 þ68.0 (c 1.16, acetone); 1H NMR (400 MHz, acetone-d6)
D
d
3.44 (3H, s, OMe), 3.68 (3H, s, OMe), 3.71 (3H, s, OMe), 3.74 (3H, s,
OMe), 3.77 (3H, s, OMe), 3.78 (6H, s, OMe), 3.79 (3H, s, OMe), 3.81
(3H, s, OMe), 3.84 (3H, s, OMe), 3.87 (9H, s, OMe), 3.96 (6H, s, OMe),
4.04 (3H, s, OMe), 4.48 (1H, ddd, J¼1.2, 6.4, 10.0 Hz, 5-H), 5.12 (1H,
dd, J¼4.0, 10.0 Hz, 2-H), 5.169 (1H, dd, A of ABX, J¼6.4, 13.2 Hz, 6-H),
5.170 (1H, t, J¼10.0 Hz, 4-H), 5.26 (1H, d, J¼4.0 Hz, 1-H), 5.85 (1H, t,
J¼10.0 Hz, 3-H), 6.52 (1H, s, Valoneoyl-H), 6.79 (1H, s, Valoneoyl-H),
7.27 (2H, s, Galloyl-H), 7.28 (2H, s, Galloyl-H), 7.32 (1H, s, Valoneoyl-
H), glu-60-H overlapped with OMe signals; 13C NMR (100 MHz,
signals; 13C NMR (100 MHz, CDCl3)
d 52.2, 55.4, 55.5, 56.0, 56.2,
56.2, 56.3, 60.6, 60.6, 60.9, 61.0, 61.0, 61.1, 61.2, 61.4, 65.2, 68.4, 68.9,
71.1, 72.4, 96.9, 97.0, 107.0, 107.2, 108.4, 109.0, 109.4, 119.3, 122.5,
124.1, 124.2, 125.6, 129.3, 129.6, 142.4, 142.6, 142.7, 146.0, 147.3,
147.5, 150.6, 151.7, 152.1, 153.0, 153.1, 153.1, 165.0, 165.2, 165.5, 165.7,
190.4; HRMS (FAB, positive ion mode) calculated for C59H69O28
[MþH]þ: 1225.3975; found: 1225.3989 [MþH]þ. To a solution of
the above aldehyde (642 mg, 0.524 mmol) in THF (6 mL) and tBuOH
(6 mL), 2-methyl-2-butene (0.557 mL, 5.24 mmol) was added at
room temperature. To the mixture, a solution of 80% NaClO2
(178 mg, 1.57 mmol) and NaH2PO4$2H2O (409 mg, 2.62 mmol) in
H2O (6 mL) was dropwise added. After stirring for 2 h, the reaction
mixture was poured into H2O (50 mL) and extracted with Et2O
(50 mLꢁ3). The combined organic layer was washed with brine
(50 mL), dried over MgSO4, and filtrated. The filtrate was evapo-
rated and the colorless residue (711 mg) was purified by silica gel
acetone-d6) d 52.5, 55.9, 56.4, 56.5, 56.6, 60.6, 60.7, 61.0, 61.0, 61.1,
61.2, 61.3, 61.7, 64.1, 67.5, 71.3, 72.2, 73.8, 98.3, 106.7, 108.1, 108.1,
109.3, 109.5, 120.6, 123.5, 124.1, 125.0, 125.3, 129.2, 129.6, 142.9,
143.8, 144.0, 145.0, 145.5, 148.0, 148.3, 151.7, 153.5, 153.8, 153.9,
154.2, 154.3, 154.3, 165.9, 166.0, 166.5, 167.8, 167.9; HRMS (FAB,
positive ion mode) calculated for C57H63O27 [MþH]þ: 1179.3557;
found: 1179.3579 [MþH]þ.
Acknowledgements
We acknowledge the gracious assistance of Prof. T. Hatano and
Dr. H. Ito (Okayama University) in providing the natural sample of 1
and a copy of NMR data for 2. The authors also thank the SC-NMR
Laboratory of Okayama University for the use of their facilities.
column chromatography (1:14:14; EtOH/EtOAc/CHCl3), providing
Supplementary data
25
34 (650 mg, quant) as a colorless amorphous: [
a
]
D
þ41.6 (c 0.61,
CHCl3); IR (CHCl3) nmax 3030, 3010, 2940, 2840, 1730, 1590, 1505,
Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2011.01.004. These data include
MOL files and InChIKeys of the most important compounds
described in this article.
1490, 1460, 1430, 1420, 1390, 1340, 1230, 1175, 1130, 1085, 1030,
1000, 920, 860, 670 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 3.31 (1H, dd,
B of ABX, J¼8.0, 10.8 Hz, 6-H), 3.38 (3H, s, OMe), 3.43 (3H, s, OMe),
3.47 (3H, s, OMe), 3.52 (3H, s, OMe), 3.66 (1H, dd, A of ABX, J¼1.2,
10.8 Hz, 6-H), 3.77 (3H, s, OMe), 3.780 (3H, s, OMe), 3.782 (6H, s,
OMe), 3.81 (3H, s, OMe), 3.856 (3H, s, OMe), 3.862 (6H, s, OMe), 3.90
(3H, s, OMe), 3.92 (3H, s, OMe), 3.94(3H, s, OMe), 3.97 (3H, s, OMe),
4.06 (3H, s, OMe), 4.63 (1H, d, B of AB, J¼6.8 Hz, OCHAHBOMe), 4.69
(1H, d, A of AB, J¼6.8 Hz, OCHAHBOMe), 5.08 (1H, dd, J¼3.2, 10.0 Hz,
2-H), 5.17 (1H, t, J¼10.0 Hz, 3 or 4-H), 5.24 (1H, d, J¼3.2 Hz, 1-H),
6.02 (1H, t, J¼10.0 Hz, 3 or 4-H), 7.05 (1H, s, Valoneoyl-H), 7.09 (2H,
s, Galloyl-H), 7.15 (1H, s, Valoneoyl-H), 7.23 (2H, s, Galloyl-H), 7.28
(1H, s, Valoneoyl-H), glu-5-H overlapped with OMe signals; 13C
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