Total synthesis of two isoflavone C-glycosides: genistein and orobol 8-C-β-d-glucopyranosides

Article abstract of DOI:10.1016/j.carres.2006.03.038

Genistein and orobol 8-C-β-d-glucopyranosides (1 and 3) were firstly synthesized in overall yields of 39% and 41% from 2,4-di-O-benzylphloroacetophenone (4), as follows: (1) the formation of the chalcone (6, 7) by aldol condensation of the benzyl-protecte

Full text of DOI:10.1016/j.carres.2006.03.038

Carbohydrate Research 341 (2006) 1091–1095
Total synthesis of two isoflavone C-glycosides: genistein and
orobol 8-C-b-D-glucopyranosides
Shingo Sato,* Kaoru Hiroe, Toshihiro Kumazawa and Onodera Jun-ichi
Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamagata University, 4-3-16 Jonan,
Yonezawa-shi, Yamagata 992-8510, Japan
Received 20 February 2006; received in revised form 21 March 2006; accepted 27 March 2006
Available online 27 April 2006
Abstract—Genistein and orobol 8-C-b-D-glucopyranosides (1 and 3) were firstly synthesized in overall yields of 39% and 41% from
2,4-di-O-benzylphloroacetophenone (4), as follows: (1) the formation of the chalcone (6, 7) by aldol condensation of the benzyl-pro-
tected C-glycosylphloroacetophenone (5), a key intermediate of the total synthesis of 1 and 3 and synthesized by a C-glycosylation
method involving the O!C glycoside rearrangement of 4 in 96% yield; (2) the formation of isoflavones (10, 11 and 12, 13) by the
formation of acetals by oxidative rearrangement of the protected chalcones (8 and 9) using Tl(NO3)3, followed by acid-catalyzed
cyclization; (3) a final debenzylation by hydrogenolysis.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Isoflavone C-glycosides; Total synthesis; C-Glycosylation; Oxidative rearrangement; O-Debenzylation
1. Introduction
are different from isoflavone aglycones that show biolog-
ical activities7 analogous to the female hormone, estro-
gen. Both are prominent bioflavonoid-type compounds.
The total synthesis of some C-glycosylflavonoids has
been reported; however, most were involved in the syn-
thesis of C-glycosylflavone.8 In spite of these various bio-
activities of isoflavone C-glycosides, the total synthesis of
2 has only been reported by Lee et al., in which b-D-gluco-
pyranosyl-2,6-dimethoxybenzene, a key intermediate in
the synthesis of 8-C-glucosyl-7,40-dihydroxyisoflavone
(puerarin 2) was synthesized by coupling a lithiated aro-
matic reagent with pyranolactone in 56% yield.9b This
synthetic method is sophisticated, but it is tedious, and
the overall yield is low. In previous studies, we reported
on the synthesis of the C-glycosylflavones, orientin and
its methyl derivatives (isoswertiajaponin, parkinsonin
A, and B),10 and isoorientin11 using 2,6-di-O-benzyl-
3-C-b-D-(2,3,4,6-tetra-O-benzyl)glucopyranosylphloro-
acetophenone (5) as the key intermediate. The
C-Glycoside 5 was synthesized by the glycosylation of
3,5-benzyl protected phloroacetophenone 4 with benzyl-
protected glucosyl fluoride in the presence of catalytic
amount of BF3ÆOEt2 in a yield of 96%.12 In this report,
we propose 5 as a candidate for a key intermediate in
Genistein 8-C-glucoside (1), a naturally occurring isoflav-
one C-glycoside, has been isolated together with puerarin
(2) from Pueraria lobota, a popular Chinese herbal med-
icine,1 and from Lupinus luteus L.,2 or from the bark of
Dalbergia nitidula Welw. ex Bak.3 Genistein 8-C-gluco-
side (1) inhibits HOCl-induced damage to human eryth-
rocytes4 and would be expected to be useful as an
antioxidant and a radioprotective agent, since it prevents
the destruction of cytochrome P-450 in a dose-dependent
manner and exerts a protective effect against gamma irra-
diation in rats.5 Orobol 8-C-glucoside (3) is also a natu-
rally occurring isoflavone C-glycoside and has been
isolated from the bark of D. monetaria as a major constit-
uent6 and from the bark of D. nitidula Welw. ex Bak.3 The
fact that 3 shows strong mitogenic and colony-stimulat-
ing, factor-inducing activities, suggests that it might act
on hematopoietic system.6 Thus, both isoflavone C-gly-
cosides have some important biological activities, which
*
Corresponding author. Tel./fax: +81 238 26 3121; e-mail: shingo-s@
yz.yamagata-u.ac.jp
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.03.038

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S. Sato et al. / Carbohydrate Research 341 (2006) 1091–1095
the total synthesis of 5,7,40-trihydroxy- and 5,7,30,40-tetra-
hydroxy-8-C-b-D-glucosylisoflavones, namely genistein
and orobol 8-C-glucosides, which have not yet been syn-
thesized. Since the final demethylation step was difficult
and gave a poor yield in the total synthesis of 2,9 our ap-
proach employs the benzyl group, which can be deprotec-
ted readily under mild hydrogenation conditions, as a
protecting group for all hydroxyl groups. In the synthesis
of 1 and 3 starting from 5, the synthesis of the chalcone by
aldol condensation with benzyl-protected hydroxybenz-
aldehydes, followed by the formation of acetals by oxida-
tive rearrangement of the chalcones and synthesis of
isoflavones by a subsequent acid-catalyzed cyclization
of the acetals, as was employed in the synthesis of 2,9 were
employed. Although thallium(III) nitrate (TTN) was
used here as a oxidant in the key oxidative rearrangement
based on the reports of Eade et al.9a and Lee et al.,9b it
might be possible to use environmentally benign and re-
cently developed diacetoxyiodobenzene (DIB) as an
alternative reagent.13 As a further final deprotecting step,
debenzylation involves much milder conditions than
those required for demethylation. We describe here the
first and effective total synthesis of two isoflavone C-
glycosides, namely genistein 8-C-b-D-glucoside (1) and
orobol 8-C-b-D-glucoside (3) (Scheme 1).
gave chalcones 6 and 7 in 98% and 92% yields, respec-
tively. After acetylation of the 2-hydroxyl group of 6
and 7 (94% and 90%), oxidative rearrangement, by treat-
ment with 2 equiv of TTN in dimethoxymethane and
methanol gave the dimethyl acetals (d 3.11, 3.35,
OMe · 2; 2.99, 3.23, OMe · 2), respectively, which were
refluxed without further purification in the presence of
a 10% HCl–methanol solution in 1,4-dioxane for 1 day,9b
to afford the desired isoflavones 10 and 12 and their 4-O-
debenzylated products 11 and 13 in a total yield of 47%
and 60% from 8 and 9, respectively. No influence of the
benzyl protecting group was observed in the oxidative
rearrangement reaction or the acid-catalyzed cyclization.
The subsequent debenzylation of 10 and 11 and 12 and 13
was performed by hydrogenolysis using 20 wt % of
Pd(OH)2/C14,8e in EtOAc and MeOH under an H2 atmo-
sphere to yield 1 and 3 in 94% and 86% yield, respectively,
without the reduction of the olefin. Under hydrogenoly-
sis using 10% Pd–C in the presence of aqueous HCl, the
yield in either case was low, 41% and 38%, respectively.
Since this debenzylation reaction proceeded in good
yield, as a consequence, the total synthesis of 1 and 3
starting from 4 was accomplished in relatively good over-
all yields of 39% and 41%, respectively. The 13C NMR
spectral data for the compounds were in agreement with
data obtained for the natural products (see Table 1).
2. Results and discussion
3. Conclusion
The aldol condensation of 5 with 4-benzyloxy- and 3,4-
dibenzyloxybenzaldehyde in 1,4-dioxane at room tem-
perature in the presence of sodium methoxide (NaOMe)
Two naturally occurring isoflavone C-glycosides,
genistein, and orobol 8-C-glucosides, were effectively
R
BnO
O
BnO
BnO
CHO
BnO
O
OBn
O
OBn
R
BnO
BnO
OBn
Ac
BnO
O
OBn
Ac
BnO
BnO
BnO
BnO
F
BnO
(a)
(b)
BnO
BnO
OBn
OBn
OR'
OH
OH
6:
8:
R, R' = H
R = H, R' = Ac
7: R = OBn, R' = H
9: R = OBn, R' = Ac
4
(c)
5
OBn
OBn
BnO
O
OH
OH
HO
O
BnO
HO
8
BnO
O
HO
9 O
(f)
(d) (e)
2
3
7
1'
6
10
4
5
4'
OR'
O
R'
O
2'
OBn
OH
3'
R
R
10: R = H, R' = Bn
11: R = H, R' = H
12: R = OBn, R' = Bn
13: R = OBn, R' = H
1: R = H, R' = OH
2: R = H, R' = H
3: R = OH, R' = OH
Scheme 1. Total synthesis of genistein and orobol C-b-D-glucosides (1, 3). Reagents and conditions: (a) BF3ÆOEt2, ꢀ78 ꢁC to rt, 5: Y 96%; (b)
MeONa in 1,4-dioxane, reflux for 20 h, 6: Y 98%, 7: Y 92%; (c) Ac2O–pyridine–DMAP, rt, 6 h, 8: Y 94%, 9: Y 90%; (d) TTN (2 equiv) in MeOH–
CHCl3, reflux for 26 h; (e) 10% HCl in MeOH–1,4-dioxane, reflux for 22 h, Y 47% (10:11 = 70:30), Y 60% (12:13 = 50:50); (f) H2–20% Pd(OH)2/C, in
EtOAc–MeOH, rt for 5 h, 1: Y 94%, 3: Y 86%.

S. Sato et al. / Carbohydrate Research 341 (2006) 1091–1095
Table 1. 13C NMR spectral data for genistein and orobol 8-C-
1093
4.2. Aldol condensation
glycosides (1 and 3)
4.2.1. 4,40,60-Tribenzyloxy-20-hydroxy-30-C-(2,3,4,6-tetra-
O-benzyl-b-D-glucopyranosyl)chalcone (6). To a solution
of 5 (1.24 g, 1.43 mmol) and p-benzyloxybenzaldehyde
(0.33 g, 1.57 mmol) in 1,4-dioxane (20 mL), was added
10 mL of a 28% NaOMe–MeOH (solution), followed
by stirring at room temperature for 20 h. The reaction
mixture was poured into 100 mL of a 2 M HCl
solution and extracted twice with EtOAc. The combined
extracts were washed with water and brine, dried over
MgSO4, and then evaporated in vacuo. The residue was
purified by flash-column chromatography on silica gel
(7:1 hexane–EtOAc) to give 6 (1.49 g, 98%) as a viscous
Compound
1
3
Carbon
Natural1
Synthetic
Natural3b Synthetic
(DMSO-d6) (CD3OD) (CD3OD) (CD3OD)
2
3
4
5
6
7
8
9
153.6
122.0
180.4
160.7
98.7
162.9
103.9
156.2
104.5
121.2
130.1
115.1
157.0
154.7
124.4
182.5
163.4
100.4
164.7
106.5
158.0
104.4
123.1
131.3
116.1
158.8
154.6
124.2
182.3
163.2
100.2
164.4
106.3
157.7
104.1
123.5
116.3
145.9
146.5
117.3
121.6
75.2
154.7
124.6
182.6
163.5
100.4
164.8
106.5
158.0
104.6
123.7
116.4
146.3
146.9
117.4
121.7
75.5
10
10
20
22
30
yellow oil: ½aꢁD ꢀ1.58 (c 1.015, CHCl3); IR (KBr) m
1
3060, 3030, 2868, 1622, 1579 cmꢀ1; H NMR (CDCl3)
40
50
d 3.50–3.68 (m, 5H, H-300, -400, -500, -600ab), 4.35 (br t,
1H, J 9.8 Hz, H-200), 4.90 (d, 1H, J 9.8 Hz, H-100), 6.50
(s, 1H, ArH), 6.91–7.51 (m, 39H, ArH), 7.61 (d, 1H, J
15.4 Hz, trans-vinyl H), 7.65 (d, 1H, J 15.4 Hz, trans-vi-
nyl H), 14.01 (br s, 1H, OH); FABMS (m/z) 1065
(M+H)+. Anal. Calcd for C70H64O10: C, 78.92; H,
6.06. Found: C, 78.54; H, 6.02.
60
G1
G2
G3
G4
G5
G6
73.1
70.5
78.4
70.2
81.3
61.2
75.4
72.8
80.1
71.8
82.6
62.9
72.7
79.9
71.6
82.3
72.9
80.1
71.8
82.7
62.7
62.9
4.2.2. 3,4,40,60-Tetrabenzyloxy-20-hydroxy-30-C-(200,300,
400,600-tetra-O-benzyl-b-D-glucopyranosyl)chalcone (7).
Chalcone 7 was produced in a yield of 88% (2.60 g)
as a viscous yellow oil from 5 (2.20 g, 2.53 mmol) and
3,4-dibenzyloxybenzaldehyde (0.97 g, 3.05 mmol) in the
same manner as for the synthesis of 6. Data for 7:
synthesized by aldol condensation of the benzyl-
protected C-b-D-glucopyranosylphloroacetophenone,
oxidative rearrangement using TTN, followed by acid-
catalyzed cyclization and a final deprotection.
21
½aꢁD ꢀ5.42 (c 0.775, CHCl3); IR (KBr) m 3062, 3030,
4. Experimental
2861, 1624, 1580, 1558, 1508, 1454, 1429, 1260, 1151,
1
1136, 1066, 1028 cmꢀ1; H NMR (CDCl3) d 3.50–3.69
The solvents used in this reaction were all prepared by
distillation. Separation and purification involved the
use of flash-column chromatography using silica gel
(230–400 mesh, Fuji-Silysia Co. Ltd, BW-300), and
column chromatography using Sephadex LH-20 gel.
Melting points were determined on a Shibayama
micro-melting point apparatus and are uncorrected.
Optical rotations were recorded on a JASCO DIP-370
polarimeter. Absorption spectra were measured using
a Hitachi U-3000 spectrophotometer. IR measurements
were achieved using a Horiba FT-720 IR spectrometer.
NMR spectra were recorded on a Varian Inova 500
spectrometer using Me4Si as the internal standard. Mass
spectra were obtained by the fast-atom bombardment
(FAB) method using 3-nitrobenzyl alcohol (NBA) as a
matrix on a JEOL JMS-AX505HA. Elemental analyses
were performed on a Perkin–Elmer PE 2400 II
instrument.
(m, 5H, H-300, -400, -500, -600ab), 4.33 (br t, 1H, J 9.9 Hz,
H-200), 4.90 (d, 1H, J 9.9 Hz, H-100), 6.49 (s, 1H, ArH),
6.88–7.48 (m, 43H, ArH), 7.57 (d, 1H, J 15.6 Hz,
trans-vinyl H), 7.62 (d, 1H, J 15.6 Hz, trans-vinyl H),
13.75 (br s, 1H, OH); FABMS (m/z) 1171 (M+H)+.
Anal. Calcd for C77H70O11: C, 78.95; H, 6.02. Found:
C, 78.76; H, 6.04.
4.3. Acetylation of chalcone
4.3.1. 20-Acetoxy-4,40,60-tribenzyloxy-30-C-(2,3,4,6-tetra-
O-benzyl-b-D-glucopyranosyl)chalcone (8). Chalcone 6
(2.69 g, 2.30 mmol) and DMAP (30 mg) were dissolved
in Ac2O (50 mL) and pyridine (18 mL) and stirred at
room temperature for 20 h. The reaction mixture was
poured into water and extracted twice with EtOAc.
The combined extracts were washed with 1 M HCl,
water, and brine, and then dried over MgSO4,
followed by evaporation. The residue was purified by
flash-column chromatography on silica gel (3:1 hexane–
EtOAc) to give 8 (2.5 g, 90%) as a pale-yellow oil:
4.1. Preparation of 5
21
Preparation of 5 was carried out according to previously
½aꢁD ꢀ23.4 (c 0.76, CHCl3); IR (KBr) m 3062, 3032,
published reports.12a,b
2923, 2862, 1774, 1603 cmꢀ1; H NMR (CDCl3) d 2.04
1

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S. Sato et al. / Carbohydrate Research 341 (2006) 1091–1095
(s, 3H, ArOAc), 3.47–4.13 (m, 5H, H-300, -400, -500, -600ab),
4.65 (dd, 1H, J 9.2, 9.8 Hz, H-200), 4.82 (d, 1H, J 9.8 Hz,
H-100), 6.41 (s, 1H, ArH), 6.82 (d, 1H, J 16.1 Hz, trans-
vinyl H), 6.86–7.45 (m, 44H, ArH and trans-vinyl H);
FABMS (m/z) 1107 (M+H)+. Anal. Calcd for
C72H66O11: C, 78.10; H, 6.01. Found: C, 77.77; H, 5.84.
4.4.2. 7,40-Dibenzyloxy-5-hydroxy-8-C-(2,3,4,6-tetra-O-
benzyl-b-D-glucopyranosyl)isoflavone (11). Pale-yellow
21
viscous oil: ½aꢁD ꢀ35.6 (c 1.280, CHCl3); IR (KBr) m
3062, 3030, 2906, 2866, 1649, 1608, 1581, 737,
1
696 cmꢀ1; H NMR (CDCl3) d 6.41, 6.42 (each s, 1H,
ArH),* 6.76–7.52 (m, 34H, ArH), 7.90 (s, 1H, H-2),
13.19, 13.24 (each s, 1H, ArOH);* FABMS (m/z) 973
(M+H)+. Anal. Calcd for C63H56O10: C, 77.76; H,
5.80. Found: C, 77.43; H, 5.51.
4.3.2. 20-Acetoxy-3,4,40,60-tetrabenzyloxy-30-C-(2,3,4,6-
tetra-O-benzyl-b-D-glucopyranosyl)chalcone
(9). The
acetylation of 7 was carried out in the same manner as
for 6 to give 9 as a pale-yellow viscous oil in a yield of
4.5. Synthesis of isoflavone system in the orobol series
22
90%: ½aꢁD ꢀ25.6 (c 1.000, CHCl3); IR (KBr) m 3062,
1
3030, 2913, 2868, 1774, 1604 cmꢀ1; H NMR (CDCl3)
The oxidative rearrangement of 9 (0.37 g) was carried
out in the same manner as for 8. A solution of the
crude oxidative-rearrangement products of 9 in 1,4-
dioxane (1 mL), MeOH (5 mL), and 10% HCl
(0.5 mL) was refluxed for 22 h. The reaction mixture
was extracted twice with toluene. The combined
extracts were washed with water and brine, then dried
over anhyd Na2SO4, and evaporated in vacuo. The
residue was separated by flash-column chromatography
on silica gel (2:1 hexane–EtOAc) to give 12 (0.12 g,
30%) and 13 (0.14 g, 30%) as a pale-yellow oil,
respectively.
d 2.03 (s, 3H, ArOAc), 3.45–4.10 (m, 5H, H-300, -400,
-500, -600ab), 4.97 (dd, 1H, J 9.2, 9.8 Hz, H-200), 4.97 (d,
1H, J 9.8 Hz, H-100), 6.37 (s, 1H, ArH), 6.79 (d, 1H, J
16.1 Hz, trans-vinyl H), 6.86–7.45 (m, 44H, ArH and
trans-vinyl H); FABMS (m/z) 1215 (M+H)+. Anal.
Calcd for C79H72O12: C, 78.19; H, 5.98. Found: C,
78.15; H, 5.83.
4.4. Synthesis of the isoflavone system in the genistein
series
TTN (0.33 g, 0.74 mmol) was added to a solution of 8
(0.41 g, 0.37 mmol) in (MeO)3CH (10 mL) and MeOH
(10 mL). The mixed solution was stirred at 40 ꢁC for
23 h and then poured into water (100 mL) and extracted
twice with toluene. The combined extracts were washed
with water and brine and then dried over anhyd MgSO4,
and evaporated in vacuo to give pale-brown solids as the
oxidative-rearrangement product that was used without
purification in the next reaction. A solution of the resi-
due in 1,4-dioxane (1 mL), MeOH (5 mL) and 10%
HCl (0.5 mL) was refluxed for 20 h. The reaction mix-
ture was extracted twice with toluene. The combined
extracts were washed with water and brine and then
dried over anhyd Na2SO4, and the solution evaporated
in vacuo. The residue was separated by flash-column
chromatography on silica gel (5:1 hexane–EtOAc) to
give the fraction including 10, which was further recrys-
tallized from Et2O–EtOAc to give 10 (0.12 g, 33%) as
pale-yellow prisms, and 11 (0.05 g, 14%) as a pale-yellow
oil.
4.5.1. 5,7,30,40-Tetrabenzyloxy-8-C-(2,3,4,6-tetra-O-benz-
yl-b-D-glucopyranosyl)isoflavone (12). Pale-yellow vis-
21
cous oil: ½aꢁD ꢀ28.3 (c 1.04, CHCl3); IR (KBr) m 3062,
1
3030, 2904, 2866, 1649, 1599, 1510, 737, 696 cmꢀ1; H
NMR (CDCl3 at 140 ꢁC) d 3.50–3.75 (m, 5H, H-
300,400,500,600ab), 4.23 (br t, 1H, J 9.5, 8.9 Hz, H-200), 5.02
(d, 1H, J 9.6 Hz, H-100), 6.80, 6.81 (s, 1H, ArH),* 6.94–
7.58 (m, 43H, ArH), 8.00 (s, 1H, H-2); FABMS (m/z)
1169 (M+H)+. Anal. Calcd for C77H68O11: C, 79.09;
H, 5.86. Found: C, 79.05; H, 6.04.
4.5.2. 7,30,40-Tribenzyloxy-5-hydroxy-8-C-(2,3,4,6-tetra-
O-benzyl-b-D-glucopyranosyl)isoflavone (13). Pale-yel-
21
low oil: ½aꢁD ꢀ22.7 (c 1.04, CHCl3); IR (KBr) m 3062,
1
3030, 2927, 2864, 1651, 1581, 1508, 737, 696 cmꢀ1; H
NMR (CDCl3) d 6.40, 6.42 (each s, 1H, ArH),* 6.85–
7.50 (m, 38H, ArH), 7.80 (s, 1H, H-2), 13.19, 13.22 (each
s, 1H, ArOH);* FABMS (m/z) 1063 (M+H)+. Anal.
Calcd for C70H62O11: C, 77.90; H, 5.79. Found: C,
77.63; H, 5.89.
4.4.1. 5,7,40-Tribenzyloxy-8-C-(2,3,4,6-tetra-O-benzyl-b-
D-glucopyranosyl)isoflavone (10). Pale-yellow prisms:
4.6. Synthesis of genistein-8-C-glucoside (1)
21
mp 148–149 ꢁC; ½aꢁD ꢀ33.9 (c 0.985, CHCl3); IR
(KBr) m 3062, 3030, 2897, 2864, 1653, 1608, 1568, 735,
To a solution of 10 (0.15 g, 0.14 mmol) and 11 (0.05 g,
0.05 mmol) in MeOH (3 mL) and EtOAc (3 mL) was
added 20 wt % of Pd(OH)2/C (20 mg). The suspension
was stirred vigorously under an H2 atmosphere for 5 h
at room temperature. The catalyst was then removed
by filtration through Celite, followed by washing with
MeOH. The filtrate was evaporated in vacuo and puri-
fied by flash-column chromatography on silica gel
1
696 cmꢀ1; H NMR (CDCl3) d 3.56–4.25 (m, 5H, H-
300,400,500,600ab), 4.23 (br t, 1H, J 9.5, 9.3 Hz, H-200), 4.50
(d, 1H, J 9.5 Hz, H-100), 6.39, 6.40 (each s, 1H, ArH),*
6.73–7.57 (m, 39H, ArH), 7.80 (s, 1H, H-2),* two peaks
were observed, corresponding to rotamers; FABMS
(m/z) 1063 (M+H)+. Anal. Calcd for C70H62O10: C,
79.07; H, 5.88. Found: C, 78.90; H, 5.67.

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8. (a) Chopin, J.; Dellamonica, G. C-Glycosylflavonoids. In
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London, 1988; pp 63–97; (b) Chopin, J.; Durix, A.;
Bouillant, M. L. Tetrahedron Lett. 1966, 3657–3661; (c)
Mahling, J.-A.; Jung, K.-H.; Schmidt, R. R. Liebigs Ann.
Chem. 1995, 461–466; (d) Frick, W.; Schmidt, R. R.
Liebigs Ann. Chem. 1989, 565–570; (e) Oyama, K.-i.;
Kondo, T. J. Org. Chem. 2004, 69, 5240–5246; (f)
Nakatsuka, T.; Tomimori, Y.; Fukuda, Y.; Nukada, H.
Bioorg. Med. Chem. Lett. 2004, 14, 3201–3203; (g) Furuta,
T.; Kimura, T.; Kondo, S.; Mihara, H.; Wakimoto, T.;
Nukada, H.; Tsuji, K.; Tanaka, K. Tetrahedron 2004, 60,
9375–9379.
(15:55:2:1 acetone–EtOAc–H2O–AcOH) and subse-
quent column chromatography on Sephadex LH-20
gel (8:2 MeOH–H2O) to give 1 (57.2 mg, 94%) as a
pale-yellow amorphous powder.
21
30
Data for 1: ½aꢁD +17.9 (c 1.005, MeOH) [½aꢁD +13.0 (c
25
0.5, DMSO),1 ½aꢁD +4.7 (c 0.52, DMSO)2]; Rf 0.38
MeOH
(15:30:2:1 acetone–EtOAc–H2O–HOAc); UV
k
max
MeOH
(loge) 263.5 nm (4.57) [k
(loge) 265 nm (4.46);1
max
264 nm (4.47)2]; IR (KBr) m 3400, 2897, 2933, 1653,
1616, 1585 cmꢀ1 13C NMR (Table 1); FABMS (m/z)
;
433 (M+H)+. Anal. Calcd for C21H20O10ÆH2O: C,
56.00; H, 4.92. Found: C, 55.86; H, 5.10.
4.7. Synthesis of orobol-8-C-glucoside (3)
Debenzylation of 12 (0.12 g, 0.10 mmol) and 13 (0.14 g,
0.13 mmol) was carried out in the same manner as for 10
and 11, and 3 was obtained in 86% yield (88.6 mg) as a
21
pale-yellow amorphous powder: ½aꢁD +14.2 (c 0.790,
MeOH), Rf 0.32 (15:30:2:1 acetone–EtOAc–H2O–
MeOH
max
MeOH
(loge) 264.5 nm (4.47) (k
max
HOAc); UV k
264 nm3b). IR (KBr)
m 3367, 2931, 1655, 1616,
9. (a) Eade, R. A.; McDonald, F. J.; Pham, H.-P. Aust. J.
Chem. 1978, 31, 2699–2706; (b) Lee, D. Y. W.; Zhang,
W.-Y.; Karnati, V. V. R. Tetrahedron Lett. 2003, 44,
6857–6859.
1577 cmꢀ1 13C NMR (Table 1); FABMS (m/z) 449
;
(M+H)+. Anal. Calcd for C21H20O11Æ0.5H2O: C,
55.14; H, 4.63. Found: C, 55.46; H, 4.92.
10. Kumazawa, T.; Kimura, T.; Matsuba, S.; Sato, S.;
Onodera, J.-i. Carbohydr. Res. 2001, 324, 183–193.
11. Kumazawa, T.; Minatogawa, T.; Matsuba, S.; Sato, S.;
Onodera, J.-i. Carbohydr. Res. 2000, 329, 507–513.
12. (a) Kumazawa, T.; Ohki, K.; Ishida, M.; Sato, S.;
Onodera, J.-i.; Matsuba, S. Bull. Chem. Soc. Jpn. 1995,
68, 1379–1384; (b) Kumazawa, T.; Kimura, T.; Matsuba,
S.; Sato, S.; Onodera, J.-i. Carbohydr. Res. 2001, 334, 183–
193; (c) Kumazawa, T.; Akutsu, Y.; Matsuba, S.; Sato, S.;
Onodera, J.-i. Carbohydr. Res. 1999, 320, 129–137; (d)
Kumazawa, T.; Saito, T.; Matsuba, S.; Sato, S.; Onodera,
J.-i. Carbohydr. Res. 2000, 329, 855–859; (e) Kumazawa,
T.; Sato, S.; Matsuba, S.; Onodera, J.-i. Carbohydr. Res.
2001, 322, 103–108; (f) Kometani, T.; Kondo, H.;
Fujimori, Y. Synthesis 1988, 1005; (g) Matsumoto, T.;
Katsuki, M.; Suzuki, K. Tetrahedron Lett. 1988, 29, 6935–
6938.
Acknowledgement
The authors gratefully acknowledge the technical assist-
ance of Mr. Hiroaki Nishizawa.
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