Synthesis of 8-C-glucosylflavones

Article abstract of DOI:10.1016/S0008-6215(01)00192-6

The syntheses of orientin, parkinsonin A, isoswertiajaponin, and parkinsonin B, which are 8-C-β-D-glucopyranosyl-3′,4′,5,7-tetrahydroxyflavone, 5-methyl orientin, 7-methyl orientin, and 5,7-dimethyl orientin, respectively, are reported herein. The C-glucosyl phloroacetophenone derivatives were obtained via a regio- and stereoselective O → C glycosyl rearrangement. Aldol condensation of the C-glucosyl phloroacetophenone derivatives with 3,4-bisbenzyloxybenzaldehyde afforded the corresponding C-glucosylchalcones. Construction of the flavone system by reaction with I₂-Me₂SO, followed by the elimination of the 5-benzyl protecting group in the flavone structure, yielded an orientin derivative and a isoswertiajaponin derivative. Methylation of the orientin derivatives with dimethyl sulfate afforded the parkinsonin A derivative, the isoswertiajaponin derivative, and the parkinsonin B derivative. Finally, hydrogenolysis of these C-glucosylflavone derivatives led to the four 8-C-glucosylflavones. The NMR spectra of these C-glucosylflavones showed a duplication of signals corresponding to a major rotamer, along with a minor one. Based on NOESY experiments in Me₂SO at ambient temperature, they adopted conformations in which the H-2″ and H-4″ protons in the glucose moiety were oriented toward the B-ring in the flavone structure.

Full text of DOI:10.1016/S0008-6215(01)00192-6

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Carbohydrate Research 334 (2001) 183–193
Synthesis of 8-C-glucosylflavones
Toshihiro Kumazawa,* Takayuki Kimura, Shigeru Matsuba, Shingo Sato,
Jun-ichi Onodera
Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamagata Uni6ersity, Jonan 4-3-16,
Yonezawa, Yamagata 992-8510, Japan
Received 6 June 2001; accepted 2 July 2001
Abstract
The syntheses of orientin, parkinsonin A, isoswertiajaponin, and parkinsonin B, which are 8-C-b-D-glucopyran-
osyl-3%,4%,5,7-tetrahydroxyflavone, 5-methyl orientin, 7-methyl orientin, and 5,7-dimethyl orientin, respectively, are
reported herein. The C-glucosyl phloroacetophenone derivatives were obtained via a regio- and stereoselective O“C
glycosyl rearrangement. Aldol condensation of the C-glucosyl phloroacetophenone derivatives with 3,4-bisbenzyloxy-
benzaldehyde afforded the corresponding C-glucosylchalcones. Construction of the flavone system by reaction with
I2–Me2SO, followed by the elimination of the 5-benzyl protecting group in the flavone structure, yielded an orientin
derivative and a isoswertiajaponin derivative. Methylation of the orientin derivatives with dimethyl sulfate afforded
the parkinsonin A derivative, the isoswertiajaponin derivative, and the parkinsonin B derivative. Finally, hydrogenol-
ysis of these C-glucosylflavone derivatives led to the four 8-C-glucosylflavones. The NMR spectra of these
C-glucosylflavones showed a duplication of signals corresponding to a major rotamer, along with a minor one. Based
on NOESY experiments in Me2SO at ambient temperature, they adopted conformations in which the H-2%%and H-4%%
protons in the glucose moiety were oriented toward the B-ring in the flavone structure. © 2001 Elsevier Science Ltd.
All rights reserved.
Keywords: C-glucosylflavone; Orientin; Isoswertiajaponin; Parkinsonin A; Parkinsonin B; Conformation
D
-glucopyranosyl-4%,5,7-trimethoxyflavone)
1. Introduction
was also reported.3 The C-glycosylation steps
were performed via a zinc oxide-promoted
A variety of plant constituents, C-Glyco-
sylflavones, have been isolated to date. These
compounds are used as natural dyestuffs, and
some are biologically active.1 Several studies
on the synthesis of C-glycosylflavones have
appeared. Following the successful total syn-
coupling using tetra-O-acetyl-a-
osyl bromide as the glycosyl donor. The syn-
thesis of 4%,7-di-O-methylisobayin (6-C-b-
glucopyranosyl-4%,7-dimethoxyflavone) has
D
-glucopyran-
D
-
also been described,4 and the synthesis of
4%,5,7-tri-O-methylvitexin was reported later.5
The C-glycosylation steps in these syntheses
were carried out by arylation using a lithiated
aromatic ring or an aromatic Grignard
reagent as the glycosyl acceptor. Harborne
and Mabry reported that the reaction of 5,7-
dihydroxyflavones with glycosyl bromides af-
forded C-glycosylflavones in one step, but in
thesis of 4%,7-di-O-methylbayin2 (8-C-b-
-
D
glucopyranosyl-4%,7-dimethoxyflavone),
the
synthesis of 4%,5,7-tri-O-methylvitexin (8-C-b-
* Corresponding author. Tel.: +81-238-263122; fax: +81-
238-263413.
E-mail address: tk111@dip.yz.yamagata-u.ac.jp, ku-
mazawa@chem.yz.yamagata-u.ac.jp (T. Kumazawa).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00192-6

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T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
low yields.6 Schmidt and co-workers reported
on the synthesis of vitexin (8-C-b- -glucopy-
ranosyl-4%,5,7-trihydoxyflavone), isovitexin (6-
C - b - - glucopyranosyl - 4%,5,7 - trihydroxyfla-
vone), and isoembigenin (8-C-b- -glucopy-
ranosyl-5-hydroxy-4%,7-dimethoxyflavone).7 A
Baker–Vankataraman-type rearrangement
are either partially or fully methylated
in the A-ring of the flavone, respectively. In
order to achieve their synthesis, the selective
methylation of the A-ring was necessary.
While the synthesis of both parkinsonin A 12
and parkinsonin B 18 have not been reported,
their isolation as natural products has been
reported by Bhatia and co-workers.11 The two
compounds, however, have not been found in
the extracts of the same source.12
D
D
D
was employed to construct the flavone system.
The C-glycosylation step in these syntheses
was carried out via an O“C glycosyl rear-
rangement. We recently reported on the syn-
thesis of isoorientin (6-C-b- -glucopyranosyl-
D
3%,4%,5,7-tetrahydroxyflavone).8 In order to
construct the 6-C-glucosyl substituted flavone
system, a selective hydrogenolysis involving
benzyl-protected and 2-methylbenzyl-pro-
tected derivatives was used.9 The C-glycosyla-
tion step in this synthesis was carried out
using boron trifluoride etherate as an activator
via an O“C glycosyl rearrangement during
the elevation of the reaction temperature,
without the isolation of the O-glycoside inter-
mediate.
2. Results and discussion
Selective protection of the commercially
available phloroacetophenone with methoxy-
methyl chloride (MOMCl) afforded the par-
tially O-protected phloroacetophenone deriva-
tive 2. After the protection of a chelated
phenolic hydroxy group of compound 2 with
benzyl chloride to afford compound 3, the
removal of both of the MOM groups of com-
pound 3 with hydrochloric acid led to the
benzyl-protected compound 4 in an overall
yield of 71% in four steps (Scheme 1).8
For the synthesis of orientin 11 and parkin-
sonin A 12, 2,4-dibenzylphloroacetophenone 5
was synthesized as the C-glucosylation accep-
tor via the regioselective benzylation of com-
pound 4 with benzyl chloride in 89% yield
(Scheme 1). Based on our previous method,8,14
compound 5 was reacted with benzyl-pro-
We herein describe the facile synthesis of
orientin 11,10 parkinsonin A 12,11,12 isoswer-
tiajaponin 17,13 and parkinsonin B 18,11,12 all
of which are 8-C-glucosylflavones. Orientin
11, 8-C-b- -glucopyranosyl-3%,4%,5,7-tetra-
D
hydroxyflavone, which is a regioisomer of
isoorientin was mentioned above and parkin-
sonin A 12 is 5-methyl orientin, isoswer-
tiajaponin 17 is 7-methyl orientin, and parkin-
sonin B 18 is 5,7-dimethyl orientin. The latter
Scheme 1.

T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
185
Scheme 2.
tected glucopyranosyl fluoride15 in the pres-
ence of boron trifluoride diethyl etherate as an
activator at low temperature, and the temper-
ature of the reaction mixture was then ele-
vated gradually to ambient temperature. The
desired synthetic intermediate 7, having a b
configuration, was obtained in nearly quanti-
tative yield, via a highly regio- and stereoselec-
tive O“C glycosyl rearrangement. The aldol
condensation of the C-glucosyl derivative 7
coal under an atmosphere of H2 to afford
orientin 11, in quantitative yield. On the other
hand, the flavone derivative 9 was methylated
with dimethyl sulfate to afford the benzyl-pro-
tected parkinsonin A 10 in 85% yield. Depro-
tection by hydogenolysis of compound 10
under the conditions described above led to a
quantitative yield of parkinsonin A 12, which
represents the desired 5-methyl orientin
(Scheme 2).
Alternatively, for the synthesis of isoswerti-
ajaponin 17 and parkinsonin B 18, which con-
tain a 7-methyl group in their orientin
structure, 2-benzyl-4-methylphloroacetophe-
none 6, a C-glucosylation acceptor was ini-
tially synthesized in 96% yield, via the
regioselective methylation of compound 4
with diazomethane (Scheme 1). The C-glu-
coside 13 was synthesized regio- and stereose-
lectively under conditions identical to those
mentioned above, in 81% yield. The aldol
condensation of the C-glucosyl derivative 13
and 3,4-bis-benzyloxybenzaldehyde in the
presence of sodium hydroxide gave the chal-
cone derivative 14 in 87% yield. The chalcone
derivative 14 was oxidized with a catalytic
amount of iodine in Me2SO, followed by
cleavage of the benzyl protection group, which
was positioned ortho to the cinnamoyl group,
and
3,4-bis-benzyloxybenzaldehyde
with
sodium hydroxide afforded the chalcone
derivative 8 in 84% yield. Selenium dioxide is
the reagent that typically used for the oxida-
tive cyclization of 2%-hydroxychalcone to the
corresponding flavone. Because the 5-hydrox-
yflavone was produced as a synthetic interme-
diate, it was necessary to convert it to the
5-methoxy flavone. This was accomplished us-
ing a catalytic amount of iodine in Me2SO,16
which involved the elimination of a benzyl
group. The chalcone derivative 8 was oxi-
dized, followed by cleavage of a benzyl-pro-
tection group that was positioned ortho to the
cinnamoyl group, to subsequently give the
partial benzyl-protected orientin 9 in 84%
yield. All benzyl-protection groups on the
flavone derivative 9 were then removed by
hydrogenolysis with 10% palladium-on-char-

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T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
1H NMR spectra of parkinsonin A 12 at
ambient temperature also showed a duplica-
tion of signals culminating in a ca. 4.0:1 ratio
of rotamer populations, based on the H-3
peaks. The anomeric proton of the main ro-
tamer appeared at 4.72 ppm (d, J1%%,2%% 9.8 Hz)
and that of the minor rotamer was at 4.92
ppm (d, J1%%,2%% 9.8 Hz). In the case of the main
rotamer of parkinsonin A 12, NOESY spectra
at ambient temperature also indicated that the
H-2%% signal in the glucose moiety of the main
rotamer was correlated to the H-2% and H-6%
signals in the B-ring of the flavone structure
and that the H-4%% signal was correlated to the
H-2% and H-6% signals. In addition, NOESY
spectra indicated a correlation between the
C-ring H-3 signal and H-2%, as well as H-6%, as
well as a correlation between the 5-methyl
to subsequently give the flavone derivative 15
in 81% yield. Deprotection of all benzyl
groups on compound 15 was carried out using
10% palladium-on-charcoal under H2 at atmo-
spheric pressure, to afford isoswertiajaponin
17, in quantitative yield, which contains a
7-methyl group. The flavone derivative 15 was
methylated with dimethyl sulfate to afford
compound 16 in 96% yield. Compound 16 was
subjected to hydrogenolysis to afford parkin-
sonin B 18 in quantitative yield, which repre-
sents the desired 5,7-dimethyl orientin
(Scheme 2).
The individual structures of the compounds
1
7–18 were confirmed by their H NMR spec-
1
tra and H–1H COSY experiments at both
ambient and elevated temperatures, as well as
by their 13C NMR and HMBC spectra at
ambient temperature for compounds 11, 12,
1
group and the H-6 aromatic proton. H NMR
spectra of parkinsonin A 12 at 140 °C showed
distinct signals, and the signal of the anomeric
proton appeared at 4.90 ppm (d, J1%%,2%% 9.8 Hz).
1H NMR spectra of isoswertiajaponin 17 at
ambient temperature also showed a duplica-
tion of signals culminating in a ca. 6.7:1 ratio
of rotamer populations, based on the H-3
peaks. The anomeric proton of the main ro-
tamer appeared at 4.72 ppm (d, J1%%,2%% 9.9 Hz)
and that of the minor rotamer was at 4.79
ppm (d, J1%%,2%% 9.6 Hz). In the case of the main
rotamer of isoswertiajaponin 17, NOESY
spectra at ambient temperature also indicated
that the H-2%% signal was correlated to the H-2%
and H-6% signals and also that the H-4%% signal
was correlated to the H-2% and H-6% signals. In
addition, the NOESY spectra indicated a cor-
relation between the H-3 and H-2%, as well as
H-6%, as well as a correlation between the
7-methyl group and the H-6 aromatic proton.
1H NMR spectra of isoswertiajaponin 17 at
150 °C showed distinct signals, and the
anomeric proton signal appeared at 4.82 ppm
(d, J1%%,2%% 9.8 Hz).
1
17, and 18. H NMR experiments were con-
ducted at elevated temperature, because, when
1
conducted at ambient temperature, the H
NMR spectra showed peaks representing the
pairing of major and minor peaks. 13C NMR
spectra at ambient temperature also showed
the pairing of individual peaks, and structural
assignments using NMR spectroscopy at am-
bient temperature were hampered by the slow
rotation around the C-1–aglycon bond.
1H NMR spectra of orientin 11 at ambient
temperature showed a duplication of signals
reminiscent of the effects of dynamic rota-
tional isomers and culminating in a ca. 4.7:1
ratio of rotamer populations, based on the
H-3 peaks. The anomeric proton of the main
rotamer appeared at 4.69 ppm (d, J1%%,2%% 9.9
Hz) and that corresponding to the minor ro-
tamer appeared at 4.84 ppm (d, J1%%,2%% 9.6 Hz).
In the case of the main rotamer, NOESY
spectra of orientin 11 at ambient temperature
indicated that the H-2%% signal in the glucose
moiety was correlated to the H-2% and H-6%
signals in the B-ring of the flavone structure,
and also that the H-4%% signal was correlated to
the H-2% and H-6% signals. The NOESY spec-
tra also indicated a correlation between the
C-ring H-3 signal and H-2%, as well as H-6%. 1H
NMR spectra of orientin 11 at 100 °C showed
distinct signals, and the signal of the anomeric
proton appeared at 4.80 ppm (d, J1%%,2%% 9.0 Hz).
1H NMR spectra of parkinsonin B 18 at
ambient temperature also showed a duplica-
tion of signals culminating in a ca. 7.7:1 ratio
of rotamer populations, based on the H-3
peaks. The anomeric proton of the main ro-
tamer appeared at 4.76 ppm (d, J1%%,2%% 9.9 Hz)
and that of the minor rotamer at 4.85 ppm (d,
J1%%,2%% 9.6 Hz). In the case of the main rotamer

T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
187
and a downfield shift of +3.1 ppm for C-3
and +3.6 ppm for C-10. In a comparison of
the 13C NMR chemical shifts of orientin 11
with that of parkinsonin B 18, the 5-methyl
group of parkinsonin B 18 produced an upfi-
eld shift of −3.6 ppm for C-2, −6.0 ppm for
C-4, and a downfield shift of +3.1 ppm for
C-3 and +4.2 ppm for C-10. In contrast to
the 13C NMR chemical shifts mentioned
of parkinsonin B 18, NOESY spectra at ambi-
ent temperature also indicated that the H-2%%
signal was correlated to the H-2% and H-6%
signals and that the H-4%% signal was correlated
to the H-2% and H-6% signals. In addition, the
NOESY spectra indicated a correlation be-
tween the H-3 and H-2%, as well as H-6%, and a
correlation between the H-6 aromatic proton
and the 5-methyl group, as well as the 7-
1
13
methyl group. H NMR spectra of parkin-
above, effects of substituents on the C NMR
sonin B 18 at 150 °C showed distinct signals,
and the signal of the anomeric proton ap-
peared at 4.86 ppm (d, J1%%,2%% 9.9 Hz).
chemical shifts of isoswertiajaponin 17 were
not observed. The hydrogen bond with the
4-keto function in orientin 11 and isoswertia-
japonin 17 produces a downfield shift in C-4
of flavone structure. Alternatively, the 5-
methyl group in parkinsonin A 12 and parkin-
sonin B 18 cause a disruption of hydrogen
bonding with the 4-keto function. As the re-
sult, due to a conjugation effect in the C-ring,
an upfield shift in C-2 and C-4 and a
downfield shift in C-3 and C-10 are apparent.
In conclusion, orientin 11, isoswertia-
japonin 17, parkinsonin A 12, parkinsonin B
18 were synthesized in relatively high yield.
Based on NOESY experiments in Me2SO at
ambient temperature, they were shown to
adopt a conformation in which the H-2%%and
H-4%% protons in the glucose moiety are ori-
ented toward the B-ring in the flavone
structure.
These approaches provided proof for the
position of the b- -glucopyranosyl moiety at
D
C-8 and, presumably, the preferred conforma-
tion for the main rotamer of the C-gluco-
sylflavones 11, 12, 17, 18 in Me2SO at ambient
temperature, in which, for the main rotamers,
the H-2%%and H-4%% protons in the glucose moi-
ety were oriented toward the B-ring in the
flavone structure, even though the 7-methyl
group is absent in orientin 11 and parkinsonin
A 12. On the contrary, based on NOE experi-
ments Rabe and co-workers determined the
preferred conformation of 8-C-(2%%,3%%,4%%,6%%-
tetra-O-acetyl-b- -glucopyranosyl)-4%,5,7-tri-
D
O-methoxyflavone in CDCl3 at 23 °C, as be-
ing similar to that of 1917, in which, in the
main rotamer, the H-1%% and H-3%% protons in
the glucose moiety are oriented toward the
B-ring in the flavone structure. Our NOESY
studies are contradictory to their conclusions.
It is known that the methylation of the
5-hydroxyl group in apigenin (4%,5,7-trihy-
droxyflavone) produces an upfield shift of 1.6
ppm of the C-5 signal and a shift of −3.7,
+4.3, and −6.1 ppm in the resonances of
C-2, -3, and -4, respectively.18 Similarly, 13C
NMR spectra show that glycosylation of the
5-hydroxy group in luteolin (3%,4%,5,7-tetra-
hydroxyflavone) has a marked effect on the
resonances of the A- and C-ring carbons.19 In
3. Experimental
General methods.—All nonaqueous reac-
tions were carried out under an atmosphere of
dry Ar using freshly distilled solvents, unless
otherwise noted. Reactions were monitored by
TLC, which was carried out on 0.25 mm Silica
Gel F254 plates (E. Merck) using either UV
light, a 5% ethanolic solution of ferric chloride
with heat as developing agents. Fuji Silysia
BW-300 was used for silica-gel column chro-
matography. Optical rotations were recorded
using either CHCl3, MeOH or pyridine as the
solvent on a JASCO DIP-370 digital polar-
imeter. IR spectra were recorded on a
HORIBA FT-720 IR spectrometer in the form
of KBr pellets. Mass spectra were recorded on
a JEOL JMS-AX-505-HA mass spectrometer
13
this study, the effect of substituents on the C
NMR chemical shifts of parkinsonin A 12 and
parkinsonin B 18, respectively, were observed
(Table 1). In a comparison of the 13C NMR
chemical shifts of orientin 11 with that of
parkinsonin A 12, the 5-methyl group of
parkinsonin A 12 produced an upfield shift of
−3.8 ppm for C-2 and − 6.0 ppm for C-4,

188
T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
ane–EtOAc), followed by recrystallization
from hexane–EtOAc to afford colorless pris-
matic crystals 5 (16.94 g, 89%): mp 108 –
109 °C; Rf 0.47 (5:1 hexane–EtOAc); IR
(KBr): w 3101, 3091, 3068, 3037, 3006, 2941,
2902, 2866, 1616, 1585, 1446, 1435, 1417,
1377, 1363, 1321, 1273, 1232, 1219, 1207,
1178, 1173, 1105, 1086, 1028, 978, 958, 904,
under electron ionization (EI) conditions or
under fast-atom bombardment (FAB) condi-
tions using 3-nitrobenzyl alcohol (NBA) or
diethanolamine as the matrix. 1H or 13C NMR
spectra were recorded on a VARIAN INOVA
500 instrument using Me4Si as an internal
reference.
2,4 - Bis - benzyloxy - 6 - hydroxyacetophenone
(5).—To a stirred solution of compound 48
(14.07 g, 54.5 mmol) and anhyd K2CO3 (8.28
g, 59.9 mmol, 1.1 equiv)) in DMF (120 mL) at
0 °C, BnCl (6.58 mL, 57.4 mmol, 1.05 equiv)
was added. After 5 min, the mixture was
allowed to warm to 25 °C, followed by stirring
for 24 h. The reaction mixture was then
poured into 1 M HCl (750 ml) and extracted
with EtOAc. The organic layer was washed
with water and brine, dried over anhyd
MgSO4 and the resulting solution evaporated
under reduced pressure. The residue was chro-
matographed on a silica gel column (8:1 hex-
839, 812, 756, 734, 692 cm−1 1H NMR
;
(CDCl3): l 2.55 (s, 3 H, ArAc), 5.061 (s, 2 H,
benzylic CH2), 5.062 (s, 2 H, benzylic CH2),
6.09 (d, 1 H, J3,5 2.4 Hz, ArH), 6.16 (d, 1 H,
J3,5 2.4 Hz, ArH), 7.33–7.42 (m, 10 H, ArH),
14.03 (s, 1 H, ArOH); EIMS: m/z 348 [M]+.
Anal. Calcd for C22H20O4: C, 75.85; H, 5.79.
Found: C, 75.95; H, 5.79.
2 - Benxyloxy - 6 - hydroxy - 4 - methoxyaceto-
phenone (6).—Compound 48 (7.00 g, 27.1
mmol) was dissolved in EtOH (500 mL) by
refluxing, and the resulting solution was
cooled at 0 °C. A diazomethane–ether solu-
Table 1
13C NMR chemical shifts a of the major rotamers of 8-C-glucopyranosylflavones 11, 12, 17, and 18
Carbon
Orientin 11
Parkinsonin A 12
Isoswertiajaponin 17
Parkinsonin B 18
Aglycon
2
3
4
5
6
7
8
164.0
102.3
181.9
160.3
98.0
162.4
104.4
155.9
103.9
121.9
114.0
145.7
149.5
115.5
119.3
160.2 (−3.8) b
105.4 (+3.1) b
175.9 (−6.0) b
159.2 (−1.1) b
95.4 (−2.6) b
160.7 (−1.7) b
105.3 (+0.9) b
157.8 (+1.9) b
107.5 (+3.6) b
122.3
164.4 (+0.4) b
102.3 (90) b
182.1 (+0.2) b
161.2 (+0.9) b
94.9 (−3.1) b
163.2 (+0.8) b
105.5 (+1.1) b
155.0 (−0.9) b
104.3 (+0.4) b
121.8
160.4 (−3.6) b
105.4 (+3.1) b
175.9 (−6.0) b
156.0 (−4.3) b
92.1 (−5.9) b
161.6 (−0.8) b
106.7 (+2.3) b
157.0 (+1.1) b
108.1 (+4.2) b
122.2
9
10
1%
2%
3%
4%
5%
6%
113.5
145.5
148.5
115.5
114.0
145.7
149.6
115.5
113.6
145.6
148.7
115.5
118.6
119.4
118.7
C-Glucopyranose
1%%
2%%
3%%
4%%
5%%
6%%
73.3
70.6
78.6
70.6
81.9
61.5
73.6
73.0
70.6
78.6
70.5
82.0
61.5
73.3
70.49 c
78.9
70.45 c
78.8
70.47 c
82.0
61.5
70.41 c
82.1
61.5
5-OMe
7-OMe
55.5
55.9
56.3
56.4
a l in ppm from TMS, in Me2SO-d6 at rt.
b Substituent effects on the 13C NMR chemical shifts of A- and C-ring in flavone structure.
c Assignments exchangeable.

T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
189
CH2), 4.50 (d, 1 H, Jgem 12.2 Hz, benzylic
CH2), 4.58 (d, 1 H Jgem 11.4 Hz, benzylic
CH2), 4.73 (d, 1 H Jgem 11.4 Hz, benzylic
CH2), 4.75 (d, 1 H Jgem 11.6 Hz, benzylic
CH2), 4.79 (d, 1 H Jgem 11.6 Hz, benzylic
CH2), 4.86 (d, 1 H, J1%,2% 9.8 Hz, H-1%), 5.17 (s,
2 H, benzylic CH2), 5.24 (d, 1 H Jgem 12.5 Hz,
benzylic CH2), 5.27 (d, 1 H Jgem 12.5 Hz,
benzylic CH2), 6.42 (s, 1 H, ArH), 6.88–7.48
(m, 30 H, ArH), 13.82 (br. s, 1 H, ArOH);
FABMS (positive-ion mode, NBA matrix): m/
z 871 [M+H]+. Anal. Calcd for C56H54O9: C,
77.22; H, 6.25. Found: C, 77.48; H, 6.23.
3,4,4%,6%-Tetrakis-benzyloxy-3%-C-(2,3,4,6-
tion was then added to the stirred solution.
After TLC monitoring showed the disappear-
ance of the starting material 4, the reaction
mixture was evaporated. The residue was re-
crystallized from hexane–EtOAc to afford
colorless prismatic crystals 6 (7.11 g, 96%): mp
117 °C; Rf 0.54 (5:1 hexane–EtOAc); IR
(KBr): w 3060, 3033, 3008, 2979, 2947, 2885,
1616, 1593, 1498, 1466, 1431, 1387, 1362,
1319, 1273, 1221, 1200, 1161, 1151, 1109,
1076, 1024, 1003, 954, 914, 899, 818, 802, 702,
1
692 cm−1; H NMR (CDCl3): l 2.56 (s, 3 H,
ArAc), 3.81 (s, 3 H, ꢀOMe), 5.08 (s, 2 H,
benzylic CH2), 6.01 (d, 1 H, J3,5 2.4 Hz, ArH),
6.08 (d, 1 H, J3,5 2.4 Hz, ArH), 7.35–7.44 (m,
5 H, ArH), 14.05 (s, 1 H, ArOH); EIMS: m/z
272 [M]+. Anal. Calcd for C16H16O4: C, 70.58;
H, 5.92. Found: C, 70.48; H, 5.84.
tetra - O - benzyl - i - - glucopyranosyl) - 2% - hy-
D
droxychalcone (8).—To a solution of com-
pound 7 (3.48 g, 3.99 mmol) and 3,4-dibenzy-
loxybenzaldehyde (1.53 g, 4.79 mmol, 1.2
equiv) in 1,4-dioxane (60 mL), a 50 wt.% aq
solution of NaOH (60 mL) was added. The
mixture was then stirred vigorously at rt for
24 h. The mixture was poured into 1 M HCl,
extracted with EtOAc, and then washed with
water and brine. The organic layer was dried
over anhyd MgSO4 and then evaporated un-
der reduced pressure. The residual orange
syrup was chromatographed on a silica gel
column (5:1 hexane–EtOAc) to afford com-
pound 8 (3.92 g, 84%) as an orange-colored
amorphous material: mp 50 °C; [h]2D5 −10° (c
1.0, CHCl3); Rf 0.40 (3:1 hexane–EtOAc); IR
(KBr): w 3088, 3062, 3030, 2929, 2901, 2861,
1624, 1580, 1555, 1509, 1453, 1430, 1331,
1260, 1235, 1210, 1151, 1135, 1101, 1065,
4,6-Bis-benzyloxy-3-C-(2,3,4,6-tetra-O-ben-
zyl-i- -glucopyranosyl)-2-hydroxyacetophen-
D
one (7).—To a stirred mixture of compound 5
(6.05 g, 17.4 mmol, 3 equiv), 2,3,4,6-tetra-O-
benzyl-a-
-glucopyranosyl fluoride15 (3.14 g,
D
,
5.79 mmol), and powdered 4 A molecular
sieves (6 g) in CH2Cl2 (60 mL) at −78 °C,
BF3·Et2O (1.43 mL, 11.6 mmol, 2.0 equiv) was
added dropwise, and the mixture was stirred
for 30 min. The temperature was allowed to
gradually increase to −42 °C, and the stirring
was continued for 30 min, then for 30 min at
−20 °C, for 30 min at 0 °C, and finally for 1
h at rt. After adding water, the resulting mix-
ture was filtered through a Celite® pad. The
filtrate was extracted with CHCl3, and the
organic layer was dried over anhyd MgSO4.
The solvent was evaporated under reduced
pressure, and the resulting syrup was chro-
matographed on a silica gel column (5:1 hex-
ane–EtOAc) to give compound 7 (4.84 g,
96%) as a pale yellowish–green highly viscous
oil: [h]2D5 −19° (c 1.0, CHCl3); Rf 0.47 (3:1
hexane–EtOAc); IR (KBr): w 3087, 3062,
3030, 3006, 2929, 2898, 2864, 1620, 1595,
1496, 1454, 1431, 1389, 1365, 1273, 1165,
1115, 1097, 1066, 1028, 1003, 910, 735, 696
1
1027, 979, 910, 845, 806, 733, 695 cm−1; H
NMR (DMSO-d6 at 120 °C): l 3.50–3.69 (m,
5 H, H-3%%,4%%,5%%,6%%a,6%%b), 4.19 (d, 1 H, Jgem
11.4 Hz, benzylic CH2), 4.33 (br. t, 1 H,
J1%%,2%%=J2%%,3%% 9.9 Hz, H-2%%), 4.45 (d, 2 H, Jgem
12.4 Hz, benzylic CH2), 4.51 (d, 1 H, Jgem 12.4
Hz, benzylic CH2), 4.58 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.73 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.76 (d, 1 H, Jgem 11.6 Hz,
benzylic CH2), 4.80 (d, 1 H, Jgem 11.6 Hz,
benzylic CH2), 4.90 (d, 1 H, J1%%,2%% 9.9 Hz,
H-1%%), 5.04 (s, 2 H, benzylic CH2), 5.18 (s, 2
H, benzylic CH2), 5.21 (s, 2 H, benzylic CH2),
5.24 (d, 1 H, Jgem 11.7 Hz, benzylic CH2), 5.26
(d, 1 H, Jgem 11.7 Hz, benzylic CH2), 6.49 (s, 1
H, ArH), 6.88–7.48 (m, 43 H, ArH), 7.57 (d,
1 H, Ja,b 15.6 Hz, trans-vinyl), 7.62 (d, 1 H,
1
cm−1; H NMR (DMSO-d6 at 120 °C): l 2.52
(s, 3 H, ArAc), 3.48–3.68 (m, 5 H, H-
3%,4%,5%,6%a,6%b), 4.16 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.31 (br. t, 1 H, J 9.0 Hz,
H-2%), 4.43 (d, 1 H, Jgem 11.4 Hz, benzylic
CH2), 4.44 (d, 1 H, Jgem 12.2 Hz, benzylic

190
T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
mixture of compound 9 (692 mg, 0.64 mmol),
Me2SO4 (152 mL, 1.60 mmol, 2.5 equiv), and
K2CO3 (354 mg, 2.56 mmol, 4.0 equiv) in
acetone (10 mL) was refluxed for 12 h. The
reaction mixture was poured into water and
then stirred for 6 h. The mixture was extracted
with EtOAc, and washed with water and
brine. The solvent was evaporated under re-
duced pressure, and the resulting syrup was
chromatographed on a silica gel column
(EtOAc) to give compound 10 (597 mg, 85%)
as a colorless amorphous powder: mp 56–
57 °C; [h]2D5 −17° (c 1.0, CHCl3); Rf 0.37
(EtOAc); IR (KBr): w 3087, 3062, 3030, 3006,
2929, 2902, 2864, 1645, 1597, 1577, 1512,
1496, 1454, 1435, 1383, 1321, 1263, 1200,
1142, 1109, 1066, 1045, 1028, 1003, 910, 845,
Ja,b 15.6 Hz, trans-vinyl), 13.75 (br. s, 1 H,
ArOH); FABMS (positive-ion mode, NBA
matrix): m/z 1172 [M+H]+; FABMS (nega-
tive-ion mode, NBA matrix): m/z 1170 [M−
H]+. Anal. Calcd for C77H70O11: C, 78.95; H,
6.02. Found: C, 78.67; H, 6.01.
2-(3,4-Bis-benzyloxyphenyl)-7-benzyloxy-8-
C-(2,3,4,6-tetra-O-benzyl-i- -glucopyranosyl)-
D
5-hydroxy-4 H-1-benzopyran-4-one (9).—A
solution of compound 8 (1.09 g, 0.93 mmol)
and iodine (11 mg, 0.04 mmol, 0.05 equiv) in
Me2SO (10 mL) was refluxed for 30 min. The
mixture was poured into water, and the result-
ing solution was extracted with EtOAc. The
organic phase was then washed with sodium
thiosulfate solution, water and brine. The or-
ganic layer was dried over anhyd MgSO4, and
the solvent was then evaporated under re-
duced pressure. The residual syrup was chro-
matographed on a silica gel column (5:1
hexane–EtOAc) to afford compound 9 (0.84
g, 84%) as a colorless amorphous powder: mp
55–56 °C; [h]2D5 −16° (c 1.0, CHCl3); Rf 0.37
(3:1 hexane–EtOAc); IR (KBr): w 3087, 3062,
3030, 3006, 2924, 2902, 2864, 1653, 1603,
1591, 1512, 1496, 1454, 1437, 1375, 1362,
1325, 1293, 1259, 1205, 1180, 1142, 1113,
1
808, 735, 696 cm−1; H NMR (DMSO-d6 at
140 °C):
l
3.59–3.77 (m,
5
H, H-
3%%,4%%,5%%,6%%a,6%%b), 3.88 (s, 3 H, ꢀOMe), 4.07 (d,
1 H, Jgem 11.5 Hz, benzylic CH2), 4.28 (br. t, J
9.5 Hz, H-2%%), 4.40 (d, 1 H, Jgem 11.5 Hz,
benzylic CH2), 4.41 (s, 2 H, benzylic CH2),
4.57 (d, 1 H, Jgem 11.5 Hz, benzylic CH2), 4.72
(d, 1 H, Jgem 11.5 Hz, benzylic CH2), 4.74 (br.
d, 1 H, Jgem 11.0 Hz, benzylic CH2), 4.78 (br.
d, 1 H, Jgem 11.0 Hz, benzylic CH2), 5.11 (d, 1
H, J1%%,2%% 9.8 Hz, H-1%%), 5.17 (s, 2 H, benzylic
CH2), 5.19 (s, 2 H, benzylic CH2), 5.25 (br. d,
1 H, Jgem 12.0 Hz, benzylic CH2), 5.28 (br. d,
1 H, Jgem 12.0 Hz, benzylic CH2), 6.51–7.60
(m, 40 H, ArH and H-3); FABMS (positive-
ion mode, NBA matrix): m/z 1094 [M+H]+.
Anal. Calcd for C71H64O11: C, 78.00; H, 5.90.
Found: C, 77.70; H, 6.08.
1066, 1028, 910, 847, 820, 808, 735, 696 cm−1
;
1H NMR (DMSO-d6 at 150 °C): l 3.59–3.71
(m, 4 H, H-4%%,5%%,6%%a,6%%b), 3.67 (br. t, 1 H, J
8.4 Hz, H-3%%), 4.11 (d, 1 H, Jgem 11.7 Hz,
benzylic CH2), 4.23 (br. t, 1 H, J 8.4 Hz,
H-2%%), 4.40 (s, 2 H, benzylic CH2), 4.43 (d, 1
H, Jgem 11.7 Hz, benzylic CH2), 4.57 (d, 1 H,
Jgem 11.2 Hz, benzylic CH2), 4.72 (d, 1 H, Jgem
11.2 Hz, benzylic CH2), 4.78 (d, 1 H, Jgem 11.7
Hz, benzylic CH2), 4.80 (d, 1 H, Jgem 11.7 Hz,
benzylic CH2), 5.05 (d, 1 H, J1%%,2%% 9.9 Hz,
H-1%%), 5.19 (s, 2 H, benzylic CH2), 5.20 (d, 1
H, Jgem 12.5 Hz, benzylic CH2), 5.21 (s, 2 H,
benzylic CH2), 5.24 (d, 1 H, Jgem 12.5 Hz,
benzylic CH2), 6.56–7.68 (m, 40 H, ArH and
H-3), 13.02 (br. s, 1 H, ArOH); FABMS
(positive-ion mode, NBA matrix): m/z 1180
[M+H]+; FABMS (negative-ion mode, NBA
matrix): m/z 1178 [M−H]+. Anal. Calcd for
C70H62O11: C, 77.90; H, 5.79. Found: C, 77.60;
H, 5.76.
8-C-i-
D
-Glucopyranosyl-2-(3,4-dihydroxy-
H-1-benzopyran-4-
phenyl)-5,7-dihydroxy-4
one; orientin (11).—A solution of compound 9
(512 mg) and 10% Pd–C (250 mg) in EtOAc
(20 mL) and EtOH (180 mL) was stirred at
ambient temperature overnight under an at-
mosphere of H2. After filtering, the filtrate was
concentrated under reduced pressure to give
orientin 11 (213 mg, quant) as a pale yellow-
ish–green powder: mp (dec) 263–264 °C, lit.12
260 °C (dec); [h]2D5 −18° (c 0.50, pyridine),
lit.12 [h]2D0 −20° (c 0.41, pyridine); Rf 0.46
(25:35:5:1 Me2CO–EtOAc–water–AcOH); IR
(KBr): w 3514, 3381, 1655, 1612, 1593, 1577,
1552, 1514, 1423, 1371, 1323, 1292, 1250,
1194, 1132, 1117, 1105, 1045, 1009, 887, 848,
2-(3,4-Bis-benzyloxyphenyl)-7-benzyloxy-8-
C-(2,3,4,6-tetra-O-benzyl-i- -glucopyranosyl)-
D
5-methoxy-4 H-1-benzopyran-4-one (10).—A

T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
191
812, 791 cm−1
;
1H NMR (DMSO-d6 at
6 (5.58 g, 20.5 mmol, 3.0 equiv), 2,3,4,6-tetra-
-glucopyranosyl fluoride15 (3.70
g, 6.83 mmol), BF3·Et2O (1.76 mL, 14.3
O-benzyl-a-
D
100 °C): l 3.33–3.37 (m, 2 H, H-3%%,5%%), 3.42
(t, 1 H, J3%%,4%%=J4%%,5%% 9.0 Hz, H-4%%), 3.61 (dd, 1
H, J5%%,6%%a 5.5, Jgem 11.9 Hz, H-6%%a), 3.77 (dd, 1
H, J5%%,6%%b 1.6, Jgem 11.9 Hz, H-6%%b), 3.86 (t, 1
H, J1%%,2%%=J2%%,3%% 9.0 Hz, H-2%%), 4.26 (br. s, 1 H,
ꢀOH), 4.49 (br. s, 3 H, ꢀOH), 4.80 (d, 1 H,
J1%%,2%% 9.0 Hz, H-1%%), 6.25 (s, 1 H, H-6), 6.54 (s,
1 H, H-3), 6.89 (d, 1 H, J5%,6% 8.2 Hz, H-5%),
7.44 (d, 1 H, J2%,6% 2.1 Hz, H-2%), 7.46 (dd, 1 H,
J2%,6% 2.1, J5%,6% 8.2 Hz, H-6%), 9.38 (br. s, 3 H,
ArOH), 13.02 (s, 1 H, ArOH); FABMS (nega-
tive-ion mode, diethanolamine matrix): m/z
447 [M−H]−. Anal. Calcd for C21H20O11: C,
56.25; H, 4.50. Found: C, 56.10; H, 4.60.
mmol, 2.0 equiv), CH2Cl2 (80 mL), and pow-
,
dered 4 A molecular sieves (6 g) were carried
out, as described above for 7, and the post-
treatment and isolation were also carried out
in the same manner. Compound 13 was ob-
tained (4.39 g, 81%) as a pale yellowish–green
highly viscous oil: [h]2D5 −12° (c 1.0, CHCl3);
Rf 0.34 (3:1 hexane–EtOAc); IR (KBr): w
3087, 3062, 3030, 3006, 2929, 2902, 2860,
1622, 1595, 1496, 1466, 1454, 1429, 1367,
1273, 1234, 1201, 1163, 1119, 1097, 1065,
1
1028, 1001, 906, 800, 735, 696 cm−1; H
NMR (DMSO-d6 at 120 °C): l 2.52 (s, 3 H,
ArAc), 3.48 (dt, 1 H, J5%,6% 3.1, J4%,5% 9.5 Hz,
H-5%), 3.57 (t, 1 H, J3%,4%=J4%,5% 9.5 Hz, H-4%),
3.65–3.68 (m, 3 H, H-3%,6%a,6%b), 3.81 (s, 3 H,
ꢀOMe), 4.16 (d, 1 H, Jgem 11.3 Hz, benzylic
CH2), 4.29 (br. t, J1%,2%=J2%,3% 9.4 Hz, H-2%),
4.45 (d, 1 H, Jgem 12.2 Hz, benzylic CH2), 4.47
(d, 1 H, Jgem 11.3 Hz, benzylic CH2), 4.55 (d,
1 H, Jgem 12.2 Hz, benzylic CH2), 4.62 (d, 1 H,
Jgem 11.4 Hz, benzylic CH2), 4.77 (d, 1 H, Jgem
11.4 Hz, benzylic CH2), 4.78 (d, 1 H, Jgem 11.6
Hz, benzylic CH2 and H-1%), 4.83 (d, 1 H, Jgem
11.6 Hz, benzylic CH2), 5.29 (s, 2 H, benzylic
CH2), 6.31 (s, 1 H, ArH), 6.89–7.50 (m, 25 H,
ArH), 13.78 (br. s, 1 H, ArOH); FABMS
(positive-ion mode, NBA matrix): m/z 795
[M+H]+; FABMS (negative-ion mode, NBA
matrix): m/z 793 [M−H]+. Anal. Calcd for
C50H50O9: C, 75.55; H, 6.34. Found: C, 75.57;
H, 6.36.
8-C-i- -Glucopyranosyl-2-(3,4-dihydroxy-
D
phenyl)-7-hydroxy-5-methoxy-4 H-1-benzopy-
ran-4-one; parkisonin A (12).—The reaction
using a compound 10 (404 mg), 10% Pd–C
(200 mg), EtOAc (10 mL) and EtOH (50 mL)
were carried out under identical conditions to
those described above, and the post-treatment
and isolation were also carried out in the same
manner as described above. Parkinsonin A 12
was obtained (171 mg, quant) as an orange
powder: mp (dec) 234–235 °C; [h]2D5 +5° (c
0.50, MeOH); Rf 0.12 (25:35:5:1 Me2CO–
EtOAc–water–AcOH); IR (KBr): w 3284,
1643, 1601, 1502, 1446, 1390, 1336, 1294,
1271, 1203, 1111, 1084, 1041, 1026, 845, 822
1
cm−1; H NMR (DMSO-d6 at 140 °C): l
3.38–3.41 (m, 2 H, H-3%%,5%%), 3.46 (t, 1 H,
J3%%,4%%=J4%%,5%% 8.0 Hz, H-4%%), 3.65 (dd, 1 H,
J5%%,6%%a 5.2, Jgem 11.4 Hz, H-6%%a), 3.77 (dd, 1 H,
J5%%,6%%b 2.6, Jgem 11.4 Hz, H-6%%b), 3.79 (s, 3 H,
ArOMe), 3.86 (t, 1 H, J1%%,2%%=J2%%,3%% 9.8 Hz,
H-2%%), 4.90 (d, 1 H, J1%%,2%% 9.8 Hz, H-1%%), 6.27
(s, 1 H, H-3), 6.43 (s, 1 H, H-6), 6.87 (d, 1 H,
J5%,6% 8.0 Hz, H-5%), 7.35 (dd, 1 H, J2%,6% 2.1, J5%,6%
8.0 Hz, H-6%), 7.36 (d, 1 H, J2%,6% 2.1 Hz, H-2%),
9.57 (br. s, 1 H, ArOH), Other phenolic ꢀOH
signals were very broad.; FABMS (positive-
ion mode, NBA matrix): m/z 463 [M+H]+;
FABMS (negative-ion mode, NBA matrix):
m/z 461 [M−H]−. Anal. Calcd for
C22H22O11: C, 57.14; H, 4.80. Found: C, 57.24;
H, 4.64.
3,4,6%-Tris-benzyloxy-3%-C-(2,3,4,6-tetra-O-
benzyl - i -
D
- glucopyranosyl) - 2% - hydroxy - 4%-
methoxychalcone (14).—The reaction using
compound 13 (3.98 g, 5.00 mmol), 3,4-diben-
zyloxybenzaldehyde (1.91 g, 6.00 mmol, 1.2
equiv), 1,4-dioxane (60 mL), and a 50 wt.% aq
solution of NaOH (60 mL), and the post-
treatment and isolation were carried out as
described above for 8. Compound 14 was
obtained (4.78 g, 87%) as an orange amor-
phous powder: mp 58–60 °C; [h]2D5 −9° (c 1.0,
CHCl3); Rf 0.28 (3:1 hexane–EtOAc); IR
(KBr): w 3087, 3062, 3030, 3006, 2935, 2900,
2860, 1624, 1579, 1558, 1508, 1496, 1454,
1429, 1383, 1360, 1331, 1261, 1209,
6-Benzyloxy-3-C-(2,3,4,6-tetra-O-benzyl-i-
-glucopyranosyl)-2-hydroxy-4-methoxyaceto-
phenone (13).—The reaction using compound
D

192
T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
benzylic CH2), 4.99 (d, 1 H, J1%%,2%%=9.6 Hz,
H-1%%), 5.19 (s, 2 H, benzylic CH2), 5.21 (s, 2
H, benzylic CH2), 6.47–7.71 (m, 35 H, ArH
and H-3), 13.07 (br. s, 1 H, ArOH); FABMS
(positive-ion mode, NBA matrix): m/z 1004
[M+H]+. Anal. Calcd for C64H58O11: C,
76.63; H, 5.83. Found: C, 76.56; H, 5.80.
2-(3,4-Bis-benzyloxyphenyl)-8-C-(2,3,4,6-
1136, 1117, 1103, 1066, 1028, 1005, 980, 908,
1
845, 806, 735, 696 cm−1; H NMR (DMSO-d6
at 140 °C): l 3.52 (dt, 1 H, J5%%,6%% 3.5, J4%%,5%% 9.5
Hz, H-5%%), 3.61 (t, 1 H, J3%%,4%%=J4%%,5%% 9.5 Hz,
H-4%%), 3.68–3.71 (m, 3 H, H-3%%,6%%a,6%%b), 3.84
(s, 3 H, ꢀOMe), 4.20 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.31 (br. t, 1 H, J 9.3 Hz,
H-2%%), 4.46 (d, 1 H, Jgem 12.3 Hz, benzylic
CH2), 4.49 (d, 1 H, Jgem 11.4 Hz, benzylic
CH2), 4.55 (d, 1 H, Jgem 12.3 Hz, benzylic
CH2), 4.63 (d, 1 H, J 11.4 Hz, benzylic CH2),
4.78 (d, 1 H, Jgem 11.4 Hz, benzylic CH2), 4.80
(d, 1 H, Jgem 11.8 Hz, benzylic CH2), 4.84 (d,
1 H, Jgem 11.8 Hz, benzylic CH2), 4.85 (d, 1 H,
J1%%,2%%=9.8 Hz, H-1%%), 5.04 (s, 2 H, benzylic
CH2), 5.17 (s, 2 H, benzylic CH2), 5.27 (s, 2 H,
benzylic CH2), 6.37 (s, 1 H, ArH), 6.89-7.46
(m, 38 H, ArH), 7.54 (d, 1 H, Ja,b 15.6 Hz,
trans-vinyl), 7.59 (d, 1 H, Ja,b 15.6 Hz, trans-
vinyl), 13.48 (br. s, 1 H, ArOH); FABMS
(positive-ion mode, NBA matrix): m/z 1096
[M+H]+. Anal. Calcd for C71H66O11: C,
77.86; H, 6.07. Found: C, 77.73; H, 6.14.
2-(3,4-Bis-benzyloxyphenyl)-8-C-(2,3,4,6-
tetra-O-benzyl-i- -glucopyranosyl)-5,7-di-
D
methoxy-4 H-1-benzopyran-4-one (16).—The
reaction using a compound 15 (804 mg, 0.80
mmol), Me2SO4 (152 mL, 1.60 mmol, 2.0
equiv), K2CO3 (443 mg, 3.21 mmol, 4.0 equiv)
and acetone (10 mL), and the post-treatment
and isolation were carried out in the same
manner as described above for 10. Compound
16 was obtained (782 mg, 96%) as a colorless
amorphous powder: mp 59–60 °C; [h]2D5 −9°
(c 1.0, CHCl3); Rf 0.26 (EtOAc); IR (KBr): w
3087, 3062, 3030, 3006, 2933, 2906, 2864,
1645, 1599, 1576, 1512, 1496, 1454, 1435,
1383, 1336, 1323, 1265, 1209, 1144, 1109,
1066, 1045, 1028, 957, 912, 845, 810, 735, 696
1
cm−1; H NMR (DMSO-d6 at 140 °C): l 3.61
(dt, 1 H, J5%%,6%% 3.2, J4%%,5%% 9.3 Hz, H-5%%), 3.71 (d,
2 H, J5%%,6%% 3.2 Hz, H-6%%a,6%%b), 3.73 (t, 1 H,
J3%%,4%%=J4%%,5%% 9.3 Hz, H-4%%), 3.78 (dd, 1 H, J2%%,3%%
8.5, J3%%,4%% 9.3 Hz, H-3%%), 3.906 (s, 3 H, ꢀOMe),
3.909 (s, 3 H, ꢀOMe), 4.06 (d, 1 H, Jgem 11.0
Hz, benzylic CH2), 4.24 (br. t, 1 H, J 9.2 Hz,
H-2%%), 4.42 (br. m, 3 H, benzylic CH2), 4.61
(d, 1 H, Jgem 11.5 Hz, benzylic CH2), 4.75 (d,
1 H, Jgem 11.5 Hz, benzylic CH2), 4.77 (d, 1 H,
Jgem 11.7 Hz, benzylic CH2), 4.81 (d, 1 H, Jgem
11.7 Hz, benzylic CH2), 5.05 (d, 1 H, J1%%,2%% 9.8
Hz, H-1%%), 5.16 (s, 2 H, benzylic CH2), 5.19 (s,
2 H, benzylic CH2), 6.50–7.65 (m, 35 H, ArH
and H-3); FABMS (positive-ion mode, NBA
matrix): m/z 1018 [M+H]+. Anal. Calcd for
C65H60O11: C, 76.75; H, 5.95. Found: C, 76.70;
H, 5.98.
tetra - O - benzyl - i -
droxy-7-methoxy-4
D
- glucopyranosyl) - 5 - hy-
H-1-benzopyran-4-one
(15).—The reaction using a compound 14
(3.18 g, 2.91 mmol), iodine (37 mg, 0.14
mmol, 0.05 equiv), and Me2SO (30 mL), and
the post-treatment and isolation were carried
out in the same manner as described above for
9. Compound 15 was obtained (2.37 g, 81%)
as a colorless amorphous powder: mp 57–
58 °C; [h]2D5 −9° (c 1.0, CHCl3); Rf 0.29 (3:1
hexane–EtOAc); IR (KBr): w 3087, 3062,
3030, 3006, 2935, 2902, 2864, 1653, 1603,
1591, 1512, 1496, 1454, 1439, 1363, 1327,
1292, 1259, 1207, 1171, 1144, 1115, 1066,
1028, 1003, 912, 847, 822, 808, 735, 696 cm−1
;
1H NMR (DMSO-d6 at 140 °C): l 3.61 (dt, 1
H, J5%%,6%% 3.2, J4%%,5%% 9.3 Hz, H-5%%), 3.70 (d, 2 H,
8-C-i- -Glucopyranosyl-2-(3,4-dihydroxy-
D
J5%%,6%% 3.2 Hz, H-6%%a,6%%b), 3.73 (t, 1 H, J3%%,4%%
=
phenyl)-5-hydroxy-7-methoxy-4 H-1-benzopy-
ran-4-one; isoswertiajaponin (17).—The reac-
tion using compound 15 (489 mg), 10% Pd–C
(240 mg), EtOAc (10 mL) and EtOH (50 mL)
were carried out as described above for 11.
Isoswertiajaponin 17 was obtained (225 mg,
quant) as a pale yellowish–green powder: mp
(dec) 217–218 °C, lit.13b 252 °C (dec); [h]2D5
−15° (c 0.50, MeOH); Rf 0.47 (25:35:5:1
Me2CO–EtOAc–water–AcOH); IR (KBr):
J4%%,5%% 9.3 Hz, H-4%%), 3.80 (dd, 1 H, J2%%,3%% 8.5,
J3%%,4%% 9.3 Hz, H-3%%), 3.87 (s, 3 H, ꢀOMe), 4.10
(d, 1 H, Jgem 11.6 Hz, benzylic CH2), 4.19 (br.
t, J 9.2 Hz, H-2%%), 4.40 (d, 1 H, Jgem 11.6 Hz,
benzylic CH2), 4.44 (d, 2 H, Jgem 11.6 Hz,
benzylic CH2), 4.61 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.75 (d, 1 H, Jgem 11.4 Hz,
benzylic CH2), 4.79 (d, 1 H, Jgem 11.5 Hz,
benzylic CH2), 4.83 (d, 1 H, Jgem 11.5 Hz,

T. Kumazawa et al. / Carbohydrate Research 334 (2001) 183–193
193
w 3392, 1655, 1601, 1520, 1498, 1448, 1429,
References
1367, 1329, 1263, 1207, 1120, 1084, 1024, 845,
1
822 cm−1; H NMR (DMSO-d6 at 150 °C): l
1. (a) Waiss, Jr., A. C.; Chan, B. G.; Elliger, C. A.; Wise-
man, B. R.; McMillian, W. W.; Widstrom, N. W.; Zuber,
M. S.; Keaster, A. J. J. Econ. Entomol. 1979, 72, 256–
258;
3.34 (m, 1 H, H-5%%), 3.37 (t, 1 H, J2%%,3%%=J3%%,4%%
8.8 Hz, H-3%%), 3.45 (br. t, 1 H, J3%%,4%%=J4%%,5%% 8.8
Hz, H-4%%), 3.62 (dd, 1 H, J5%%,6%%a 5.6, Jgem 11.7
Hz, H-6%%a), 3.79 (dd, 1 H, J5%%,6%%b 2.6, Jgem 11.7
Hz, H-6%%b), 3.88 (s, 3 H, ArOMe), 3.97 (dd, 1
H, J2%%,3%% 8.8, J1%%,2%% 9.8 Hz, H-2%%), 4.82 (d, 1 H,
J1%%,2%% 9.8 Hz, H-1%%), 6.45 (s, 1 H, H-6), 6.53 (s,
1 H, H-3), 6.91 (d, 1 H, J5%,6% 8.7 Hz, H-5%),
7.447 (s, 1 H, H-2%), 7.452 (br. d, 1 H, J5%,6% 8.7
Hz, H-6%), 8.50 (br. s, 1 H, ArOH), 9.00 (br. s,
1 H, ArOH), 13.09 (s, 1 H, ArOH); FABMS
(positive-ion mode, NBA matrix): m/z 463
[M+H]+; FABMS (negative-ion mode, NBA
matrix): m/z 461 [M−H]−. Anal. Calcd for
C22H22O11·0.5 H2O: C, 56.05; H, 4.92. Found:
C, 56.43; H, 5.04.
(b) Elliger, C. A.; Chan, B. G.; Waiss, Jr., A. C.; Lundin,
R. E.; Haddon, W. F. Phytochemistry 1980, 19, 293–297;
(c) Carte, B. K.; Carr, S.; DeBrosse, C.; Hemling, M. E.;
MacKenzie, L.; Offen, P.; Berry, D. E. Tetrahedron 1991,
47, 1815–1822;
(d) Besson, E.; Dellamonica, G.; Chopin, J.; Markham,
K. R.; Kim, M.; Koh, H.-S.; Fukami, H. Phytochemistry
1985, 24, 1061–1064;
(e) Haribari, M.; Renwick, J. A. A. Phytochemistry 1998,
47, 1237–1240;
(f) Afifi, F. U.; Khalil, E.; Abdalla, S. J. Ethnopharmacol.
1999, 65, 173–177.
2. Eade, R. A.; McDonald, F. J.; Simes, J. J. H. Aust. J.
Chem. 1975, 28, 2011–2018.
3. Eade, R. A.; Pham, H. P. Aust. J. Chem. 1979, 32,
2483–2493.
4. Tschesche, R.; Widera, W. Liebigs Ann. Chem. 1982,
902–907.
5. Frick, W.; Schmidt, R. R. Liebigs Ann. Chem. 1989,
8-C-i- -Glucopyranosyl-2-(3,4-dihydroxy-
D
565–570.
phenyl)-5,7-dimethoxy-4 H-1-benzopyran-4-
one; parkisonin B (18).—The reaction using a
compound 16 (617 mg), 10% Pd–C (300 mg),
EtOAc (10 mL) and EtOH (50 mL) were
carried out as described above for 11. Parkin-
sonin B 18 was obtained (289 mg, quant) as a
pale pink powder: mp (dec) 221–222 °C; [h]D25
−11° (c 0.50, MeOH); Rf 0.04 (25:35:5:1
Me2CO–EtOAc–water–AcOH); IR (KBr): w
3392, 1639, 1599, 1522, 1497, 1448, 1394, 1327,
6. Harborne, J. B.; Mabry, T. J. The Fla6onoids: Ad6ances
in Research, 1st ed.; Chapman and Hall: London, 1982;
pp. 449–503.
7. Mahling, J.-A.; Jung, K.-H.; Schmidt, R. R. Liebigs Ann.
Chem. 1995, 461–466.
8. Kumazawa, T.; Minatogawa, T.; Matsuba, S.; Sato, S.;
Onodera, J. Carbohydr. Res. 2000, 329, 507–513.
9. Davis, R.; Muchowski, J. M. Synthesis 1982, 987–988.
10. Leitao, S. G.; Monache, F. D. Phytochemistry 1998, 49,
2167–2169.
11. Bhatia, V. K.; Gupta, S. R.; Seshadri, T. R. Tetrahedron
1966, 22, 1147–1152.
1275, 1215, 1120, 1084, 1038, 847, 816 cm−1
;
12. Besson, E.; Chopin, R.; Gunasegaran, R.; Nair, A. G. R.
Phytochemistry 1980, 19, 2787–2788.
13. (a) Wallace, J. W.; Morris, G. Phytochemistry 1978, 17,
1809–1810;
1H NMR (DMSO-d6 at 150 °C): l 3.34 (ddd, 1
H, J5%%,6%%b 2.4, J5%%,6%%a 5.2, J4%%,5%% 9.0 Hz, H-5%%),
3.37 (t, 1 H, J2%%,3%%=J3%%,4%% 8.7 Hz, H-3%%), 3.46
(br. s, 1 H, H-4%%), 3.63 (dd, 1 H, J5%%,6%%a 5.2, Jgem
11.6 Hz, H-6%%a), 3.79 (dd, 1 H, J5%%,6%%b 2.4, Jgem
11.6 Hz, H-6%%b), 3.89 (s, 3 H, 5-OMe), 3.92 (s,
3 H, 7-OMe), 4.02 (dd, 1 H, J2%%,3%% 8.7, J1%%,2%% 9.9
Hz, H-2%%), 4.86 (d, 1 H, J1%%,2%% 9.9 Hz, H-1%%),
6.30 (s, 1 H, H-3), 6.61 (s, 1 H, H-6), 6.88 (d,
1 H, J5%,6% 8.9 Hz, H-5%), 7.39 (br. s, 2 H,
H-2%,6%). phenolic ꢀOH signals were very
broad.; FABMS (positive-ion mode, NBA ma-
trix): m/z 477 [M+H]+; FABMS (negative-
ion mode, NBA matrix): m/z 475 [M−H]−.
Anal. Calcd for C23H24O11·0.5 H2O: C, 56.91;
H, 5.19. Found: C, 57.05; H, 5.35.
(b) Fujita, M.; Inoue, T. Chem. Pharm. Bull. 1982, 30,
2342–2348;
(c) Webby, R. F.; Markham, K. R. Phytochemistry 1994,
36, 1323–1326.
14. Kumazawa, T.; Akutsu, Y.; Matsuba, S.; Sato, S.;
Onodera, J. Carbohydr. Res. 1999, 320, 129–137.
15. Hayashi, M.; Hashimoto, S.; Noyori, R. Chem. Lett.
1984, 1747–1750.
16. Silva, A. M. S.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.
Tetrahedron Lett. 1994, 35, 5899–5902.
17. Rabe, C.; Steenkamp, J. A.; Joubert, E.; Burger, J. F. W.;
Ferreira, D. Phytochemistry 1994, 35, 1559–1565.
18. Harborne, J. B.; Mabry, T. J. The Fla6onoids: Ad6ances
in Research, 1st ed.; Chapman and Hall: London, 1982;
pp. 19–134.
19. Markham, K. R.; Ternai, B.; Stanley, R.; Geiger, H.;
Mabry, T. J. Tetrahedron 1978, 34, 1389–1397.
.