Regioselective synthesis of 6-alkyl- and 6-prenylpolyhydroxyisoflavones and 6-alkylcoumaronochromone derivatives

Article abstract of DOI:10.1248/cpb.52.1285

The palladium-catalyzed coupling reaction of 6-iodoisoflavone, prepared from 3′-iodoacetophenone derivative, with 2-methyl-3-butyn-2-ol gave 6-alkynylisoflavone derivative, which was hydrogenated to give 6-alkylhydroxyisoflavone (luteone hydrate) (2). Dehydration of 2 gave 2′,4′,5,7-tetrahydroxy-6-prenylisoflavone (luteone) (1). Wighteone hydrate (3) was also synthesized from 6-iodotris(benzyloxy)isoflavone in a similar manner. 6-Alkyl-4′5,7-trihydroxy-coumaronochromone (4) was synthesized by oxidative cyclization of 2 with o-chloranil.

Full text of DOI:10.1248/cpb.52.1285

November 2004
Chem. Pharm. Bull. 52(11) 1285—1289 (2004)
1285
Regioselective Synthesis of 6-Alkyl- and 6-Prenylpolyhydroxyisoflavones
and 6-Alkylcoumaronochromone Derivatives
*
Masao TSUKAYAMA, Hironari WADA, Yasuhiko KAWAMURA, Kazuyo YAMASHITA, and
Masaki NISHIUCHI
Department of Chemical Science and Technology, Faculty of Engineering, The University of Tokushima; Minamijosanjima-
cho, Tokushima 770–8506, Japan. Received April 23, 2004; accepted July 14, 2004
The palladium-catalyzed coupling reaction of 6-iodoisoflavone, prepared from 3ꢀ-iodoacetophenone deriva-
tive, with 2-methyl-3-butyn-2-ol gave 6-alkynylisoflavone derivative, which was hydrogenated to give 6-alkylhy-
droxyisoflavone (luteone hydrate) (2). Dehydration of 2 gave 2ꢀ,4ꢀ,5,7-tetrahydroxy-6-prenylisoflavone (luteone)
(1). Wighteone hydrate (3) was also synthesized from 6-iodotris(benzyloxy)isoflavone in a similar manner. 6-
Alkyl-4ꢀ5,7-trihydroxy-coumaronochromone (4) was synthesized by oxidative cyclization of 2 with o-chloranil.
Key words iodoisoflavone; prenylisoflavone; luteone; regioselective prenylation; coumaronochromone; o-chloranil
coumaronochromone (4), which is considered to be a precur-
sor of lupinalbin B, has yet to be isolated from natural
sources. We have examined the simple and general applica-
bility of DDQ or o-chloranil to the synthesis of alkylpolyhy-
droxycoumaronochromones from the corresponding 2ꢁ-hy-
droxyisoflavones.18) We wish to report here the synthesis of
compound 4 by oxidative cyclization of compound 2 with o-
chloranil.
Prenyl (ꢀ3-methyl-2-butenyl)isoflavones and (3-hydroxy-
3-methylbutyl)isoflavones, which contain an alkyl or alkenyl
group in the A- and/or B-ring, are widely distributed in na-
ture and have antifungal activity.1—4) Luteone, known as a
phytoalexin, was first isolated in 1973 from immature fruits
of Lupinus luteus (Leguminosae).5) The structure was as-
signed as 2ꢁ,4ꢁ,5,7-tetrahydroxy-6-(3-methyl-2-butenyl)iso-
flavone (1) by spectroscopic and chemical studies. The same
isoflavone 1 was also isolated from healthy leaves or roots of
white lupin (Lupinus albus L., cv Kievskij Mutant)4,6) and the
roots of yellow lupin (Lupinus leuteus L., cv. Barpin) to-
gether with luteone hydrate, the structure of which was as-
signed to be 2ꢁ,4ꢁ,5,7-tetrahydroxy-6-(3-hydroxy-3-methyl-
butyl)isoflavone (2) by spectroscopic analysis.7) Luteone hy-
drate (2) was isolated as a fungal metabolite of luteone (1)
with cultures of Aspergillus flavus and Botrytis cinerea.8)
Wighteone hydrate [4ꢁ,5,7-trihydroxy-6-(3-hydroxy-3-methyl-
butyl)isoflavone] (3) was also isolated as a fungal metabolite
of wighteone [4ꢁ,5,7-trihydroxy-6-(3-methyl-2-butenyl)iso-
flavone]2,6,7,9) with cultures of A. flavus and B. cinerea.10) In
view of the isolation of 1 and 2 from the same natural source,
it is considered that 2 is a precursor of 1 and dehydration of 2
would lead to 1. The total syntheses of isoflavones 1, 2, and
3 have not been achieved yet, although the dimethyl ether
of luteone (1) has been synthesized.11) The reason seems to
be due to the difficulty in introducing an alkyl or alkenyl
group regioselectively into the isoflavone nucleus and the
selectivity of protection and consequent deprotection. Fur-
thermore, 6-alkylpolyhydroxyisoflavones are isomerized to
the corresponding isomers, 8-alkylpolyhydroxyisoflavones,
by bases.12,13) We need to solve these problems for the re-
gioselective synthesis of these phloroglucin-type 6-prenyl-
isoflavones. In our previous paper,14) we reported the regiose-
lective synthesis of prenylisoflavones. As a continuation of
our studies on the regioselective synthesis of alkyl- and
prenylisoflavones, we wish to report here on the first synthe-
ses of 1, 2, and 3 using the palladium (0)-catalyzed coupling
reaction15) of the corresponding iodoisoflavone with 2-methyl-
3-butyn-2-ol.16) Recently, the new coumaronochromones
(ꢀbenzofuro[2,3-b][1]benzopyran-11-ones) lupilutin (8-alkyl-
coumaronochromone from the root of yellow lupin)7) and
lupinalbin B (6-prenylcoumaronochromone from the root of
white lupin)17) have also been isolated. However, 6-alkyl-
Results and Discussion
The catalytic hydrogenation of 2ꢁ,4ꢁ-bis(benzyloxy)-6ꢁ-
methoxymethoxyacetophenone14) over Pd/C, followed by io-
dination of the resulting 2ꢁ,4ꢁ-dihydroxyacetophenone 5 with
I2 and H5IO619) gave the 3ꢁ-iodoacetophenone 6 in 92% yield.
Compound 6 was converted into bis(benzyloxy)acetophe-
none 7, the structure of which was determined by direct com-
parison with a sample of the isomer [2ꢁ,4ꢁ-bis(benzyloxy)-5ꢁ-
iodo-6ꢁ-methoxymethoxyacetophenone (mp 99—100 °C)14)]
1
and H-NMR-NOE analysis. The mixture of 7 with the iso-
mer showed a marked decrease in the melting point relative
to that of each compound. Compound 7 was not obtainable
by the I2-CF3CO2Ag method.14) Condensation of 7 with 2,4-
bis(benzyloxy)benzaldehyde in the presence of sodium hy-
droxide gave 6ꢁ-methoxymethoxychalcone 8, and then the
methoxymethyl group in the chalcone was cleaved by treat-
ment with dilute HCl to give 3ꢁ-iodo-6ꢁ-hydroxychalcone 9
in 86% yield. Oxidative rearrangement of acetate 10, pre-
pared from 9, with thallium(III) nitrate trihydrate (TTN),20)
followed by hydrolysis of the resulting mixture 11 with aque-
ous sodium hydroxide gave the desired 6-iodoisoflavone 12
in 40% yield and the chalcone 9, the structures of which
were identified by 1H-NMR spectral analysis. On the basis of
the results, it was shown that deacetylation of 10 with TTN
took place more easily than the oxidative rearrangement of
the phenyl group of 10 to give the chalcone 9. Therefore 9
was converted into benzoate 13, which was oxidatively re-
arranged with TTN to give the corresponding acetal 14 eas-
ily. The crude acetal 14 was hydrolyzed with aqueous sodium
hydroxide to give the 6-iodoisoflavone 12 in 70% yield via
two steps from 13. The coupling reaction of 12 with 2-
methyl-3-butyn-2-ol in the presence of Pd(0) in triethylamine
gave 6-(3-hydroxy-3-methylbutynyl)isoflavone 15 in 71%
yield. The catalytic hydrogenation of 15 gave 2ꢁ,4ꢁ,5,7-
∗ To whom correspondence should be addressed. e-mail: tukayama@chem.tokushima-u.ac.jp
© 2004 Pharmaceutical Society of Japan

1286
Vol. 52, No. 11
Chart 1
Table 1. 1H-NMR (400 MHz, CD3COCD3) Data for Prenyl- and Alkylisoflavones 1, 2, Luteone, and Luteone Hydratea)
6ꢁ-H
Compound
2-H
8-H
3ꢁ-H
5ꢁ-H
Me
CH2
CHꢀC
OH
2ꢁ-H
1
8.14 s
8.14 s
8.15 s
6.53 s
6.53 s
6.52 s
6.48 d
(Jꢀ2.4)
6.48 d
6.44 dd
(Jꢀ2.4, 8.3) (Jꢀ8.3)
6.43 dd 7.12 d
7.12 d
1.65 s
1.78 s
1.65 s
1.78 s
1.26 s
(6H)
3.37 d
(Jꢀ7.3)
3.37 br d
(Jꢀ7.3)
1.71 m
5.28 t
(Jꢀ7.3)
5.28 br t
(Jꢀ7)
8.31 br s, 8.43 br s
9.23 br s, 13.06 s
13.05 s
Natural product7)
(1)
2
(Incomplete) (Jꢀ2.4, 8.9) (Jꢀ8.9)
6.49 d
(Jꢀ2.4)
6.44 dd
(Jꢀ2.4, 8.3) (Jꢀ8.3)
7.12 d
3.59 br s
2.79 m
8.32 s, 8.43 s
9.29 br s, 13.05 s
13.04 s
Natural product7)
8.14 s
8.15 s
6.51 s
6.47 s
6.48 d
6.43 dd
7.12 d
1.25 s
(6H)
1.26 s
(6H)
1.71 m
2.81 m
1.71 m
2.78 m
(2)
3
(Incomplete) (Jꢀ2.4, 8.8) (Jꢀ8.8)
6.90 d
(Jꢀ8.8)
6.90 d
(Jꢀ8.8)
7.45 d
(Jꢀ8.8)
7.45 d
8.50 br s, 9.65 br s
13.33 s
(Jꢀ8.8)
a) s, singlet; d, doublet; dd, double doublet; t, triplet; br, broad; m, multiplet.
tetrahydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone (2) in The tosylate 17 was dehydrated with TsOH·H2O to give a
1
96% yield. The H-NMR spectrum of 2 was identical to that mixture of 6-prenylisoflavone 18 and the regioisomer 6-(3-
1
of a natural sample of luteone hydrate7) (Table 1) and other methyl-3-butenyl)isoflavone 21. The H-NMR spectrum of
physical properties (see Experimental). On the basis of these the tosylate mixture (18 and 21) showed the ratio of 18 to 21
results, the structure of luteone hydrate was confirmed by to be 85 : 15 [peaks due to CH2CHꢀC(CH3)2 at dꢀ3.36 (2H,
the first synthesis of 2ꢁ,4ꢁ,5,7-tetrahydroxy-6-(3-hydroxy-3- d) and CH2CH2C(CH3)ꢀCH2 at dꢀ4.57 (2H, s)]. The mix-
methylbutyl)isoflavone (2).
ture (18 and 21) reacted quantitatively with benzohydroxi-
Exhaustive benzoylation (7 h) of 2 afforded partly the moyl chloride14) in dry CH2Cl2 at room temperature to give a
isomer [2ꢁ,4ꢁ,7-tris(benzoyloxy)-5-hydroxy-8-(3-hydroxy-3- mixture of the unchanged 6-prenylisoflavone 18 and the ter-
methylbutyl)isoflavone]. To prevent the isomerization, the minal alkene-cyclic adduct, and then 18 was purified by sil-
partial benzoylation of compound 2 gave 2ꢁ,4ꢁ,7-tris(benzoyl- ica gel column chromatography. The detosylation of 18 with
oxy)isoflavone 16 for 30 min in 85% yield, and subsequently BCl3, followed by hydrolysis of the resultant compound 19
compound 16 was tosylated for 20 min to give 5-tosyloxy- with 10% NaOH in a mixture of methanol and dioxane at
isoflavone 17 in 91% yield. Compound 17 was dehydrated room temperature, gave 2ꢁ,4ꢁ,5,7-tetrahydroxy-6-(3-methyl-
with BF3·OEt2 at room temperature to give 6-prenyl-5-tosyl- 2-butenyl)isoflavone (1) in 66% yield (1H-NMR in Table 1),
oxyisoflavone 18 (20%), 5-hydroxy-6-prenylisoflavone 19 which was converted into the tetraacetate derivative 22. The
(25%), and dihydropyran derivative 20 (45%), respectively. 1H-NMR, IR, and UV spectral data for 1 were completely
In this reaction, it was shown that part of 18 was initially identical to those of a natural sample of luteone.5,6) On the
detosylated, and the resulting compound 19 was subse- basis of these results, the structure of luteone was confirmed
quently cyclized to give 20. The formation of 20 strongly for the first time by the synthesis of 2ꢁ,4ꢁ,5,7-tetrahydroxy-6-
supported the structure of 2 and decreased the yield of 19. (3-methyl-2-butenyl)isoflavone (1).

November 2004
1287
Chart 2
Condensation of 7 with 4-benzyloxybenzaldehyde and the ica gel column chromatography (AcOEt : hexaneꢀ2 : 1 as a solvent) and re-
crystallized from a mixture of AcOEt and hexane to give dihydroxyace-
tophenone 5 (2.28 g, 94%) as colorless needles, mp 118—120 °C; H-NMR
(CDCl3) dꢀ2.65 (3H, s, COCH3), 3.52 (3H, s, OCH3), 5.25 (2H, s,
OCH2O), 5.25 (1H, s, C4ꢁ-OH), 6.04 (1H, d, Jꢀ2.4 Hz, Ar-H), 6.14 (1H, d,
subsequent hydrolysis of the resultant chalcone 23 gave 6ꢁ-
hydroxychalcone 24, which was converted into the corre-
sponding benzoate 25. The oxidative rearrangement of 25
1
with TTN for 20 h, followed by the hydrolysis of the resultant
acetal 26, gave the corresponding 4ꢁ-benzyloxy-6-iodo-
isoflavone 27 in 30% yield via three steps from 24. The yield
of compound 27 was lower than that of the 2ꢁ,4ꢁ-bis(benzyl-
oxy)-6-iodoisoflavone 12. The reason depends on the number
of the electron-releasing subtituents in the B-ring.12,21)
The coupling reaction of 27 with 2-methyl-3-butyn-2-ol in
the presence of Pd(0) gave 6-(3-hydroxy-3-methyl-1-bu-
tynyl)isoflavone 28 in 57% yield. The catalytic hydrogena-
tion of 28 over Pd/C gave 4ꢁ,5,7-trihydroxy-6-(3-hydroxy-3-
methylbutyl)isoflavone (3) in 92% yield. The 1H-NMR spec-
trum and other physical properties were identical to those of
a natural sample of wighteone hydrate10) (Table 1). On the
basis of these results, the structure of wighteone hydrate was
confirmed by the synthesis of 4ꢁ,5,7-trihydroxy-6-(3-hy-
droxy-3-methylbutyl)isoflavone (3).
The oxidative cyclization of the 2ꢁ-hydroxyisoflavone 2
with o-chloranil (2.2 eq) [the reduction potential (0.83 V) is
lower than that (1.0 V) of DDQ]22,23) in dioxane gave the de-
sired coumaronochromone 4 at 80 °C for 2 h in good yield.
Compound 4 was easily converted into diacetate 29 at 0 °C
using the acetic anhydride-pyridine method.
The present regioselective synthesis of iodoisoflavones
and the palladium (0)-catalyzed coupling reaction of
iodoisoflavones with 2-methyl-3-butyn-2-ol have been shown
to be efficient and useful procedures for the syntheses of
prenyl- and alkylpolyhydroxyisoflavones and O-alkylated
prenylisoflavones.
Jꢀ2.4 Hz, Ar-H), 13.79 (1H, s, C6ꢁ-OH). Anal. Calcd for C10H12O5: C,
56.60; H, 5.70. Found: C, 56.61; H, 5.60.
2ꢀ,4ꢀ-Dihydroxy-3ꢀ-iodo-6ꢀ-methoxymethoxyacetophenone (6) The
acetophenone 5 (3.16 g, 14.8 mmol) was dissolved in EtOH (30 ml), and io-
dine (1.88 g, 7.4 mmol) and periodic acid (674 mg, 3 mmol) in water (10 ml)
were added to the solution; the mixture was then stirred for 30 min at 40 °C.
The mixture was cooled and diluted with water to give compound 6 as color-
less needles (4.63 g, 92%), mp 160—161 °C; 1H-NMR (CDCl3) dꢀ2.69
(3H, s, COCH3), 3.52 (3H, s, OCH3), 5.28 (2H, s, OCH2O), 5.98 (1H, s, C4ꢁ-
OH), 6.44 (1H, s, C5ꢁ-H), 14.97 (1H, s, C2ꢁ-OH). Anal. Calcd for C10H11IO5:
C, 35.52; H, 3.28. Found: C, 35.23; H, 3.17.
2ꢀ,4ꢀ-Bis(benzyloxy)-3ꢀ-iodo-6ꢀ-methoxymethoxyacetophenone (7) To
a mixture of 6 (1.0 g, 2.95 mmol), K2CO3 (2.03 g, 15 mmol), and DMF
(8 ml), a solution of benzyl chloride (0.75 ml, 6.5 mmol) in DMF (1 ml) was
added dropwise with stirring under nitrogen at 70 °C for 30 min. The reac-
tion mixture was extracted with CHCl3, washed with diluted HCl and water,
and dried (Na2SO4). The resulting compound was recrystallized from a mix-
ture of MeOH and AcOEt to yield 7 (623 mg, 80%) as colorless needles, mp
96—98 °C; 1H-NMR (CDCl3) dꢀ2.47 (3H, s, COCH3), 3.46 (3H, s, OCH3),
4.97 (2H, s, ArCH2O), 5.15 (2H, s, OCH2O), 5.18 (2H, s, ArCH2O), 6.65
(1H, s, C5ꢁ-H), 7.32—7.60 (10H, m, Ar-Hꢂ10). Anal. Calcd for C24H23IO5:
C, 55.61; H, 4.47. Found: C, 55.66; H, 4.48.
2,4,2
ꢀ,4
ꢀ-Tetrakis(benzyloxy)-3ꢀ-iodo-6ꢀ-methoxymethoxychalcone (8)
and 2,4,2
ꢀ
,4 -Tetrakis(benzyloxy)-6
ꢀ
ꢀ-hydroxy-3ꢀ-iodochalcone (9)
A
mixture of the acetophenone 7 (1.84 g, 3.54 mmol) and 2,4-bis(benzyloxy)-
benzaldehyde (1.70 g, 5.3 mmol) was stirred in the presence of KOH (2.0 g,
35 mmol) in EtOH (120 ml) at 80 °C for 45 min. Ice-water and 10% HCl
were added to the reaction mixture to give 6ꢁ-methoxymethoxychalcone 8 as
yellow precipitates. The collected crude solid 8 was dissolved in a mixture
of CHCl3 (60 ml) and MeOH (60 ml). Concentrated HCl (3 ml) was added to
the solution, and then the mixture was stirred at 40 °C for 1 h. The whole so-
lution was extracted with CHCl3, and the chloroform extract was washed
with water and dried (Na2SO4). After removal of the solvent, the resulting
compound was recrystallized from a mixture of CHCl3 and MeOH to give
6ꢁ-hydroxychalcone 9 (2.35 g, 86% from 7) as yellow needles, mp 158—
160 °C; 1H-NMR (CDCl3) dꢀ4.82, 5.00, 5.07, and 5.20 (each 2H, s,
Experimental
All the melting points were measured on a Yanaco MP-J3 micro melting- PhCH2), 6.38 (1H, dd, Jꢀ2.4 and 8.8 Hz, C5-H), 6.41 (1H, s, C5ꢁ-H), 6.54
point apparatus and are uncorrected. The 1H-NMR spectra were measured (1H, d, Jꢀ2.4 Hz, C3-H), 7.1—7.53 (21H, m, Ar-Hꢂ20, C6-H), 7.90, and
with a JEOL EX400 spectrometer (400 MHz), using tetramethylsilane as in- 8.29 (each 1H, d, Jꢀ15.6 Hz, CHꢀ), 13.77 (1H, s, C2-OH). Anal. Calcd for
ternal standard (d, ppm). The IR spectra were recorded on a Hitachi 215
spectrophotometer, and the UV spectra were recorded on a Hitachi 124 spec-
trophotometer. Elemental analyses were performed with a Yanaco CHN
C43H35IO6: C, 66.67; H, 4.55. Found: C, 66.43; H, 4.62.
6ꢀ-Acetoxy-2,4,2ꢀ,4ꢀ-tetrakis(benzyloxy)-3ꢀ-iodochalcone (10) and
2ꢀ,4ꢀ,5,7-Tetrakis(benzyloxy)-6-iodoisoflavone (12) The chalcone 9 (540
corder model MT-5. Column chromatography and thin-layer chromatogra- mg, 0.70 mmol) was converted into acetate 10 at 70 °C for 30 min using an
phy (TLC) were carried out on Kieselgel 60 (70—230 mesh) and Kieselgel
60 F-254 (Merck).
acetic anhydride (20 ml)-pyridine (2 ml) method. After the addition of water
to the reaction mixture, the whole mixture was extracted with CHCl3 and the
2ꢀ,4ꢀ-Dihydroxy-6ꢀ-methoxymethoxyacetophenone (5) 2ꢁ,4ꢁ-Bis(ben- extract was washed with water and dried (Na2SO4). After the resulting ac-
zyloxy)-6ꢁ-methoxymethoxyacetophenone (4.5 g, 11.46 mmol) was hy- etate 10 (530 mg) and TTN (420 mg, 0.9 mmol) were stirred in a solution of
drogenolyzed over Pd/C (5%) (450 mg) in MeOH (100 ml) and AcOEt
(100 ml) at 18—23 °C until uptake of hydrogen ceased. After removal of the added to the reaction mixture, and the whole solution was stirred at room
solvent under reduced pressure, the resulting compound was purified by sil-
temperature for 1 h to give white precipitates. After removal of the precipi-
MeOH (25 ml) and CHCl3 (10 ml) at 30 °C for 4 h, 10% HCl (15 ml) was

1288
Vol. 52, No. 11
(ꢄNaOAc) 273sh, 269 (4.44), and 340 (3.93). Anal. Calcd for C20H20O7: C,
64.51, H, 5.41. Found: C, 64.22; H, 5.46.
tates by filtration, the filtrate was extracted with CHCl3, and the extract was
washed with water and dried (Na2SO4). The resulting crude acetal 11 in
dioxane (10 ml) and MeOH (10 ml) was stirred with 10% aqueous NaOH
(8 ml) at room temperature for 2 h, and then water and 10% HCl were added
to the reaction mixture to give precipitates. The collected precipitates were
extracted with CHCl3, washed with water, and dried (Na2SO4). The resulting
compound was chromatographed over a silica gel flash column (CHCl3 as a
solvent) to give the isoflavone 12 (218 mg, 40% from 9), and recrystallized
from a solution of MeOH and CHCl3) as pale yellow needles, mp 174—
176.5 °C.
2ꢀ,4ꢀ,7-Tris(benzoyloxy)-5-hydroxy-6-(3-hydroxy-3-methylbutyl)iso-
flavone (16) A mixture of 2 (420 mg, 1.12 mmol), benzoyl chloride (0.47
ml, 4 mmol), and K2CO3 (1.55 g, 11 mmol) in Me2CO (20 ml) was refluxed
with stirring under nitrogen for 30 min. After removal of K2CO3 and the sol-
vent, the residue was extracted with ethyl acetate, washed with 5% HCl and
water, and dried (Na2SO4). The resulting compound was purified by silica
gel column chromatography (CHCl3 : Me2COꢀ10 : 1 as a solvent) and fur-
ther recrystallized from a mixture of MeOH and AcOEt to give 16 (650 ml,
1
85%) as pale yellow needles, mp 154—155 °C; H-NMR (CDCl3) dꢀ1.19
2,4,2ꢀ,4ꢀ-Tetrakis(benzyloxy)-6ꢀ-benzoyloxy-3ꢀ-iodochalcone (13)
A
(6H, s, CH3ꢂ2), 1.69 and 2.72 (each 2H, m, CH2), 6.84 (1H, s, C8-H),
7.26—7.70 (13H, m, Ar-Hꢂ13), 7.98 (1H, s, C2-H), 8.1—8.25 (5H, m, Ar-
Hꢂ5), 12.92 (1H, s, C5-OH). Anal. Calcd for C41H32O10: C, 71.92; H, 4.71.
Found: C, 71.91; H, 4.78.
mixture of the chalcone 9 (3.0 g, 3.87 mmol), benzoyl chloride (0.68 ml,
5.9 mmol), and K2CO3 (2.68 g, 19 mmol) in DMF (35 ml) was stirred under
nitrogen at 60 °C for 30 min. After removal of K2CO3 and the solvent under
reduced pressure, the residue was extracted with CHCl3, washed with 10%
HCl and water, and dried (Na2SO4). The resulting compound was purified by
silica gel column chromatography (CHCl3 : hexaneꢀ10 : 1 as a solvent) and
further recrystallized from MeOH–Me2CO to give 13 (3.18 g, 92%) as pale
yellow needles, mp 126—128 °C; 1H-NMR (CDCl3) dꢀ4.99, 5.01, 5.04,
and 5.18 (each 2H, s, PhCH2), 6.51 (1H, s, C3-H), 6.53 (1H, s, C5-H), 6.77
(1H, s, C5ꢁ-H), 7.03 and 7.79 (each 1H, d, Jꢀ16.1 Hz, CHꢀ), 7.20—8.10
(25H, m, Ar-Hꢂ25). Anal. Calcd for C50H39IO7: C, 68.34; H, 4.47. Found:
C, 68.13; H, 4.70.
2ꢀ,4ꢀ,7-Tris(benzoyloxy)-6-(3-hydroxy-3-methylbutyl)-5-tosyloxy-
isoflavone (17) A mixture of 16 (820 mg, 1.19 mmol), TsCl (342 mg, 1.8
mmol), and K2CO3 (1.66 g, 12 mmol) in Me2CO (35 ml) was refluxed with
stirring under nitrogen for 20 min. After removal of K2CO3 and the solvent,
the residue was extracted with AcOEt, washed with 5% HCl and water, and
dried (Na2SO4). The resulting compound was recrystallized from a mixture
of CHCl3 and MeOH to give 17 (906 mg, 91%) as colorless needles, mp
116—119 °C; 1H-NMR (CDCl3) dꢀ1.13 (6H, s, CH3ꢂ2), 1.39 (1H, s, OH),
1.71 and 2.82 (each 2H, m, CH2), 2.45 (3H, s, Ar-CH3), 7.26—7.70 (15H,
m, Ar-Hꢂ15), 7.87 (1H, s, C2-H), 7.9—8.2 (8H, m, Ar-Hꢂ8). Anal. Calcd
for C48H38O12S: C, 68.73; H, 4.57. Found: C, 68.47; H, 4.76.
Dehydration of 2ꢀ,4ꢀ,7-Tris(benzoyloxy)-6-(3-hydroxy-3-methylbutyl)-
5-tosyloxyisoflavone (17) with Boron Trifluoride Diethyl Etherate To a
solution of 17 (50 mg, 0.06 mmol) in dry CH2Cl2 (2 ml) was added a solution
of BF3·OEt2 (0.05 mmol) in CH2Cl2 (0.4 ml); the mixture was stirred under
nitrogen at room temperature for 2 h. To the reaction mixture was added
aqueous NH4Cl, and the whole solution was extracted with chloroform,
washed with water, and dried (Na2SO4). The resulting compound was chro-
matographed over a silica gel column (CHCl3 as a solvent) to give 5-tosyl-
oxyisoflavone 18 [10 mg (20%) as colorless needles, mp 188—189 °C], 5-
hydroxyisoflavone 19 [10 mg (25%) as pale yellow needles, mp 177—
179 °C], and dihydropyranoisoflavone 20 [18 mg (45%) as colorless prisms],
mp 187—190 °C; 1H-NMR (CDCl3) dꢀ1.41 (6H, s, CH3ꢂ2), 1.81 and 2.68
(each 2H, t, Jꢀ6.8 Hz, CH2), 6.81 (1H, s, C8-H), 7.2—7.7 (12H, m, Ar-H),
7.81 (1H, s, C2-H), 8.09—8.23 (6H, m, Ar-H). Anal. Calcd for C41H30O9: C,
73.87; H, 4.54. Found: C, 73.65; H, 4.80.
1-[6-Benzoyloxy-2,4-bis(benzyloxy)-3-iodophenyl]-2-[2,4-bis(benzyl-
oxy)phenyl]-3,3-dimethoxypropan-1-one (14) and 2,4,2ꢀ,4ꢀ-Tetrakis(ben-
zyloxy)-6-iodoisoflavone (12) A mixture of the chalcone 13 (1.61 g, 1.83
mmol) and TTN (1.24 g, 2.8 mmol) was stirred in a solution of MeOH
(150 ml) and CHCl3 (60 ml) at 40 °C for 4 h, then 10% HCl (35 ml) was
added to the mixture at room temperature and the whole was further stirred
at that temperature for 1 h to give white precipitates. After removal of the
precipitates by filtration, the filtrate was extracted with CHCl3 and the ex-
tract was washed with water and dried (Na2SO4). The organic solvent was
removed under reduced pressure, and the resulting crude acetal 14 was dis-
solved in a mixture of dioxane (80 ml) and MeOH (100 ml), and then hy-
drolyzed with 10% aqueous NaOH at room temperature for 2 h. Water and
10% HCl were added to the reaction mixture to give precipitates. The col-
lected precipitates were extracted with CHCl3, washed with water, and dried
(Na2SO4). The resulting compound was chromatographed over a silica gel
column (CHCl3 as a solvent) to give the 6-iodoisoflavone 12, which was re-
crystallized from a mixture of MeOH and CHCl3 as pale yellow needles
(995 mg, 70% from 13), mp 174—176 °C; 1H-NMR (CDCl3) dꢀ5.02, 5.03,
5.05, and 5.25 (each 2H, s, PhCH2), 6.63 (1H, dd, Jꢀ2.4 and 8.5 Hz, C5ꢁ-H),
6.67 (1H, d, Jꢀ2.4 Hz, C3ꢁ-H), 6.73 (1H, s, C8-H), 7.20—7.75 (21H, m, Ar-
Hꢂ21), 7.78 (1H, s, C2-H). Anal. Calcd for C43H33IO6: C, 66.85; H, 4.30.
Found: C, 66.64; H, 4.58.
2ꢀ,4ꢀ,7-Tris(benzoyloxy)-6-(3-methyl-2-butenyl)-5-tosyloxyisoflavone
(18) To a solution of 17 (1.0 g, 1.19 mmol) in dry toluene (6 ml) was added
TsOH·H2O (1.81 ml of a 5.25ꢂ10ꢃ1 mol dmꢃ3 in acetic acid); the mixture
was stirred under nitrogen at 110 °C for 45 min. The reaction mixture was
extracted with ether, washed with 5% aqueous NaHCO3, 2% HCl, and water,
and dried (Na2SO4). The resulting compound was chromatographed over a
silica gel-flashed column (CHCl3 as a solvent) to give a mixture of 6-
1
Acetal 14: mp 56—58 °C; H-NMR (CDCl3) dꢀ2.92 and 3.14 (each 3H,
s, OCH3), 4.7—5.0 (6H, m, PhCH2ꢂ3), 5.09 (2H, s, PhCH2), 5.15 and 5.47
(each 1H, d, Jꢀ8.8 Hz, CH), 6.25 (1H, dd, Jꢀ3 and 8.6 Hz, Ar-H), 6.37 (1H,
d, Jꢀ3 Hz, Ar-H), 6.54 (1H, s, Ar-H), 7.09 (1H, d, Jꢀ8.6 Hz, Ar-H), 7.05—
8.15 (25H, m, Ar-Hꢂ25).
1
alkenylisoflavones (745 mg) as colorless needles. The H-NMR spectrum of
the mixture was shown to be an 85 : 15 mixture of the 6-(3-methyl-2-
butenyl)isoflavone 18 and the isomer 6-(3-methyl-3-butenyl)isoflavone 21.
The mixture (18 and 21) in CH2Cl2 (0.5 ml) was added to a solution of
benzohydroximoyl chloride (63 mg, 0.4 mmol) and NEt3 (0.13 ml, 0.94
mmol) in CH2Cl2 (2 ml) in an ice-bath, and then the reaction mixture was
stirred at room temperature for 20 h. The reaction mixture was quenched
with saturated aqueous NH4Cl and extracted with CH2Cl2, washed with
water, and dried (Na2SO4). The resulting compound was chromatographed
over a silica gel column (CHCl3 : Me2COꢀ15 : 1 as a solvent) to give the 6-
prenylisoflavone 18, which was recrystallized from a mixture of CHCl3 and
2ꢀ,4ꢀ,5,7-Tetrakis(benzyloxy)-6-(3-hydroxy-3-methyl-1-butynyl)iso-
flavone (15) To a solution of 12 (1.5 g, 1.94 mmol) and 2-methyl-3-butyn-
2-ol (0.56 ml, 6 mmol) in a mixture of NEt3 (25 ml) and DMF (9 ml), were
added PdCl2 (17 mg, 0.1 mmol), PPh3 (51 mg, 0.19 mmol), and CuI (18 mg,
0.1 mmol); the mixture was then stirred under nitrogen at 75 °C for 2 h. The
reaction mixture was filtered through charcoal and the filtrate was concen-
trated under reduced pressure and extracted with AcOEt; the extract was
then washed with 2% HCl and water and dried (Na2SO4). The resulting com-
pound was purified by silica gel column chromatography (CHCl3 : AcOEt
ꢀ10 : 1 as a solvent) and further recrystallized from a mixture of MeOH and
1
hexane as colorless needles (500 mg, 68% from 17), mp 188—189 °C; H-
1
NMR (CDCl3) dꢀ1.38 and 1.45 (each 3H, s, CH3), 2.44 (3H, s, Ar-CH3),
3.36 (2H, d, Jꢀ6.4 Hz, CH2), 4.92 (1H, br t, Jꢀ6.4 Hz, ꢀCH), 7.2—7.7
(15H, m, Ar-Hꢂ15), 7.86 (1H, s, C2-H), 8.0—8.2 (8H, m, Ar-Hꢂ8). Anal.
Calcd for C48H36O11S: C, 70.23; H, 4.42. Found: C, 70.19; H, 4.59.
Me2CO to give 15 (1.32 g, 71%) as colorless prisms, mp 173—174°C; H-
NMR (CDCl3) dꢀ1.51 (6H, s, CH3ꢂ2), 5.04, 5.06, 5.15, and 5.20 (each 2H,
s, PhCH2), 6.68 (1H, d, Jꢀ2.4 Hz, C3ꢁ-H), 6.69 (1H, s, C8-H), 7.20—7.70
(21H, m, Ar-Hꢂ21), 7.77 (1H, s, C2-H). Anal. Calcd for C48H40O7: C,
79.10; H, 5.53. Found: C, 78.86; H, 5.63.
2ꢀ,4ꢀ,5,7-Tetrahydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone (Luteone
Hydrate) (2) The isoflavone 15 (2.31 g, 3.17 mmol) was hydrogenolyzed
over Pd/C (5%) (400 mg) in MeOH (120 ml) and dioxane (100 ml) at room
temperature until uptake of hydrogen ceased. After removal of the solvent
under reduced pressure, the resulting compound was recrystallized from a
mixture of MeOH and CH2Cl2 to give 2 (1.13 g, 96%) as pale yellow prisms,
mp 229—231 °C; IR (KBr) n 3350, 2975, 1645, 1620, 1460, 1310, 1065,
and 830 cmꢃ1; UV lmax nm (log e) (MeOH) 265 (4.45), 290sh (4.19), and
347sh (3.58); (ꢄAlCl3) 208sh (3.53), 240sh (4.10), and 267 (4.46);
2ꢀ,4ꢀ,7-Tris(benzoyloxy)-5-hydroxy-6-(3-methyl-2-butenyl)isoflavone
(19) A mixture of 18 (160 mg, 0.19 mmol) and BCl3 (0.14 ml; 1 mol solu-
tion: Aldrich) on dry CH2Cl2 (2 ml) was stirred under argon at 15 °C for
15 min. The reaction mixture was quenched with saturated NH4Cl and ex-
tracted with CH2Cl2, washed with water, and dried (Na2SO4). The resulting
compound was purified by silica gel column chromatography (CHCl3 as a
solvent) and crystallized fron CHCl3–hexane to give 19 (123 mg, 95%) as
1
pale yellow needles, mp 177—179 °C; H-NMR (CDCl3) dꢀ1.55 and 1.59
(each 3H, s, CH3), 3.34 (2H, d, Jꢀ7.3 Hz, CH2), 5.12 (1H, t, Jꢀ7.3 Hz,
ꢀCH), 6.80 (1H, s, C8-H), 7.3—7.7 (15H, m, Ar-Hꢂ15), 7.97 (1H, s, C2-

November 2004
1289
H), 8.1—8.2 (6H, m, Ar-Hꢂ6), 12.90 (1H, s, C5-OH). Anal. Calcd for chromone (29) To a dioxane solution (12 ml) of the 2ꢁ-hydroxyisoflavone
C41H30O9: C, 73.87; H, 4.54. Found: C, 73.73; H, 4.76. 2 (350 mg; 0.93 mmol), o-chloranil (303 mg, 1.2 mmol) was added and
2ꢀ,4ꢀ,5,7-Tetrahydroxy-6-(3-methyl-2-butenyl)isoflavone (Luteone) (1) stirred at 80 °C for 10 min, and subsequently o-chloranil (305 mg, 1.2 mmol)
Compound 19 (150 mg, 0.22 mmol) in MeOH (2 ml) and dioxane (2 ml) was was again added to the mixture, and the whole was stirred at 80 °C for 2 h.
hydrolyzed with 10% aqueous NaOH (2 ml) under argon at room tempera- After removal of the solvent, unreacted o-chloranil was removed by silica
ture for 1 h. To the reaction mixture water and diluted HCl were added; the gel column chromatography (AcOEt : CHCl3ꢀ2 : 1 as a solvent) and the ob-
organic solvent was then evaporated under reduced pressure. The residue tained coumaronochromone 4 was converted into the diacetate 29 by treat-
was extracted with ether, washed with water, and dried (Na2SO4). The com- ment with acetic anhydride (20 ml)–pyridine (1.5 ml) at 0 °C for 30 min. The
pound was chromatographed over a silica gel column (CHCl3 : AcOEtꢀ2 : 1
as a solvent) to give 6-prenylisoflavone 1 (52 mg, 66%), which was crystal-
resulting compound was purified by silica gel column chromatography
(AcOEt : CHCl3ꢀ2 : 1 as a solvent) to give 29 (205 mg, 61% via two steps
lized from CH2Cl2–hexane as pale yellow prisms, mp 223—225°C; IR from 2) as colorless needles, mp 271—274 °C; 1H-NMR (CDCl3) dꢀ1.31
(KBr) n 3425, 3300, 3100 br., 1650, 1615, 1590, 1550, 1215, 1060,
(6H, s, CH3ꢂ2), 1.55 (1H, s, OH), 1.71 and 2.73 (each 2H, m, CH2), 2.36
and 2.39 (each 3H, s, COCH3), 6.87 (1H, s, C8-H), 7.20 (1H, dd, Jꢀ1.9 and
815 cmꢃ1; UV lmax nm (log e) (MeOH) 266 (4.56), 280 (4.33), 340 (3.63),
(ꢄAlCl3) 271 (4.41), (ꢄNaOAc) 269 (4.55), 340 (3.83). Anal. Calcd for 8.3 Hz, C5ꢁ-H), 7.39 (1H, d, Jꢀ1.9 Hz, C3ꢁ-H), 8.08 (1H, d, Jꢀ8.3 Hz, C6ꢁ-
C20H18O6: C, 67.79; H, 5.12. Found: C, 67.55; H, 5.21.
2ꢀ,4ꢀ,5,7-Tetraacetoxy-6-(3-methyl-2-butenyl)isoflavone (22) Compound
1 (159 mg, 0.45 mmol) was converted into tetraacetate 22 by treatment with
H), 13.16 (1H, s, C5-OH). Anal. Calcd for C24H22O9: C, 63.43; H, 4.88.
Found: C, 63.53; H, 4.85.
4ꢀ,5,7-Trihydroxy-6-(3-hydroxy-3-methylbutyl)coumaronochromone
acetic anhydride (2 ml)-pyridine (0.3 ml) at 110 °C for 2 h. The resulting (4) Compound 29 (120 mg, 0.26 mmol) in a mixture of MeOH–dioxane
compound was purified by silica gel column chromatography (AcOEt :
was hydrolyzed with 10% aqueous NaOH at room temperature for 1 h. The
hexaneꢀ2 : 1 as a solvent) to give 22 as colorless pastes (188 mg, 80%); 1H- resulting compound was recrystallized from a mixture of H2O and MeOH to
NMR (CDCl3) dꢀ1.68 and 1.75 (each 3H, s, CH3), 2.16, 2.30, 2.36, and give 4 (66 mg, 67%) as colorless needles, mp 260—262 °C; 1H-NMR
2.40 (each 3H, s, COCH3), 3.23 (2H, br d, CH2), 5.00 (1H, br t, ꢀCH), (DMSO-d6) dꢀ1.16 (6H, s, CH3ꢂ2), 1.52 and 2.61 (each 2H, m, CH2), 4.18
7.04—7.29 (4H, m, Ar-H), 7.80 (1H, s, C2-H).
4,2 ,4 -Tris(benzyloxy)-6 -hydroxy-3 -iodochalcone (24) A mixture of 7.11 (1H, d, Jꢀ2.0 Hz, C3ꢁ-H), 7.74 (1H, d, Jꢀ8.9 Hz, C6ꢁ-H), 9.94 and
the acetophenone 7 (300 mg, 0.58 mmol) and 4-benzyloxybenzaldehyde 10.80 (each 1H, br s, OH), 13.13 (1H, s, C5-OH). Anal. Calcd for C20H18O7:
(1H, br s, OH), 6.61 (1H, s, C8-H), 6.92 (1H, dd, Jꢀ2.0 and 8.9 Hz, C5ꢁ-H),
ꢀ
ꢀ
ꢀ
ꢀ
(188 mg, 0.9 mmol) in EtOH (50 ml) was stirred in the presence of KOH
C, 64.86; H, 4.90. Found: C, 64.69; H, 4.82.
(330 mg, 6 mmol) at 80 °C for 1 h. The resulting 6ꢁ-methoxymethoxychal-
cone 23 was worked up in the same manner as in the case of the 6ꢁ-hydroxy- References and Notes
chalcone 8 to 6ꢁ-hydroxy-4-benzyloxychalcone 24, which was recrystallized
from a mixture of CHCl3 and MeOH as yellow needles (334 mg, 87% via
two steps from 7), mp 124—125 °C; 1H-NMR (CDCl3) dꢀ4.86, 5.10 and
5.21 (each 2H, s, PhCH2), 6.24 (1H, s, C5-H), 6.84 (2H, d, Jꢀ8.8 Hz, C3-
and C5-H), 6.99—7.53 (17H, m, Ar-H), 7.83 and 7.88 (each 2H, d, Jꢀ15.4
Hz, CHꢀ), 13.57 (1H, s, C6-OH). Anal. Calcd for C36H29IO5: C, 64.68; H,
4.37. Found: C, 64.47; H, 4.61.
1) Dewick P. M., “The Flavonoids: Advances in Research Since 1980,”
ed. by Harborne J. B., Chapman and Hall, London,1988.
2) Ingham J. L., Tahara S., Harborne J. B., Z. Naturforsch. 38c, 194—200
(1983).
3) Woodward M. D., Phytochemistry, 18, 363—365 (1979).
4) Harborne J. B., Ingham J. L., King L., Payne M., Phytochemistry, 15,
1485—1487 (1976).
4ꢀ,5,7-Tris(benzyloxy)-6-iodoisoflavone (27) A mixture of 24 (300 mg,
0.45 mmol), benzoyl chloride (0.08 ml, 0.7 mmol), and K2CO3 (433 mg,
3.1 mmol) in DMF (8 ml) was stirred under the same conditions as in the
case of the benzoate 13 to give 6ꢁ-benzoyloxy-3ꢁ-iodochalcone 25. A mix-
ture of 25 and TTN (300 mg, 0.68 mmol) was stirred in a solution of MeOH
(25 ml) and CHCl3 (10 ml) at 40 °C for 20 h. The resulting crude acetal 26 in
dioxane (10 ml) and MeOH (10 ml) was hydrogenated with 10% aqueous
NaOH at room temperature for 2 h. The reaction mixture was worked up in
the same manner as in the case of the 6-iodoisoflavone 12 to give 4ꢁ,5,7-
tris(benzyloxy)-6-iodoisoflavone 27, which was recrystallized from a mix-
ture of CHCl3 and MeOH as pale yellow needles (86 mg, 30% via three
5) Fukui H., Egawa H., Koshimizu K., Mitsui T., Agric. Biol. Chem., 37,
417—421 (1973).
6) Tahara S., Ingham J. L., Nakahara S., Mizutani J., Harborne J. B., Phy-
tochemistry, 23, 1889—1900 (1984).
7) Hashidoko Y., Tahara S., Mizutani J., Agric. Biol. Chem., 50, 1797—
1807 (1986).
8) Tahara S., Nakahara S., Mizutani J., Ingham J. L., Agric. Biol. Chem.,
48, 1471—1477 (1984).
9) Ingham J. L., Keen N. T., Hymowitz T., Phytochemistry, 16, 1943—
1946 (1977).
10) Tahara S., Nakahara S., Ingham J. L., Mizutani J., Nippon Nôgeika-
gaku Kaishi, 59, 1039—1044 (1985).
11) Jain A. C., Kumar A., Gupta R. C., J. Chem. Soc., Perkin Trans. 1,
1979, 279—287 (1979).
1
steps from 24), mp 154—157 °C; H-NMR (CDCl3) dꢀ5.07, 5.10 and 5.27
(each 2H, s, PhCH2), 6.75 (1H, s, C8-H), 7.04 (2H, d, Jꢀ8.8 Hz, C3ꢁ- and
C5ꢁ-H), 7.30 (15H, m, Ar-H), 7.77 (2H, d, Jꢀ8.8 Hz, C2ꢁ- and C6ꢁ-H), 7.81
(1H, s, C2-H). Anal. Calcd for C37H27IO5: C, 64.87; H, 4.08. Found: C, 12) Tsukayama M., Kawamura Y., Tamaki H., Kubo T., Horie T., Bull.
64.65; H, 4.23.
Chem. Soc. Jpn., 62, 826—832 (1989).
4ꢀ,5,7-Tris(benzyloxy)-6-(3-hydroxy-3-methylbutynyl)isoflavone (28)
To a solution of 27 (640 mg, 0.96 mmol) and 2-methyl-3-butyn-2-ol (0.28
ml, 3 mmol) in a mixture of NEt3 (15 ml) and DMF (5 ml) were added PdCl2
(8.5 mg, 0.05 mmol), PPh3 (25 mg, 0.1 mmol), and CuI (9.1 mg, 0.05 mmol);
the mixture was then stirred under nitrogen at 80 °C for 1 h. The reaction
mixture was worked up in the same manner as in the case of the 6-
alkynylisoflavone 15 to give 6-(3-hydroxy-3-methylbutynyl)isoflavone 28,
13) Varady J., Tetrahedron Lett., 48, 4273—4275 (1965).
14) Tsukayama M., Li H., Tsurumoto K., Nishiuchi M., Kawamura Y.,
Bull. Chem. Soc. Jpn., 71, 2673—2680 (1998).
15) Sonogashira K., Tohda Y., Hagihara N., Tetrahedron Lett., 50, 4467—
4470 (1975).
16) Tsukayama M., Wada H., Kishida M., Nishiuchi M., Kawamura Y.,
Chem. Lett., 2000, 1362—1363 (2000).
which was recrystallized from a mixture of MeOH and Me2CO as colorless 17) Tahara S., Ingham J. L., Mizutani J., Agric. Biol. Chem., 49, 1775—
needles (340 mg, 57%), mp 171—173 °C; 1H-NMR (CDCl3) dꢀ1.50 (6H, s,
1783 (1985).
CH3ꢂ2), 1.78 (1H, s, OH), 5.10 and 5.21 (6H, s, PhCH2ꢂ3), 6.72 (1H, s, 18) Tsukayama M., Oda A., Kawamura Y., Nishiuchi M., Yamashita K.,
C8-H), 7.03 (2H, d, Jꢀ8.3 Hz, C3ꢁ- and C5ꢁ-H), 7.30—7.52 (15H, m, Ar-H), Tetrahedron Lett., 42, 6163—6166 (2001).
7.67 (2H, d, Jꢀ8.3 Hz, C2ꢁ- and C6ꢁ-H), 7.79 (1H, s, C2-H). Anal. Calcd for 19) Ahluwalia V. K., Prakash C., Jolly R. S., J. Chem. Soc., Perkin Trans.
C41H34O6: C, 79.08; H, 5.50. Found: C, 78.94; H, 5.53. 1, 1981, 1697—1702 (1981).
4ꢀ,5,7-Trihydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone (Wighteone 20) Farkas L., Gottsegen À., Nórgrádi M., Antus S., J. Chem. Soc., Perkin
Hydrate) (3) The isoflavone 28 (720 mg, 1.15 mmol) in a solution of Trans. 1, 1974, 305—312 (1974).
MeOH (30 ml) and dioxane (30 ml) was hydrogenolyzed over Pd/C (5%) 21) Horie T., Shibata K., Yamashita K., Fujii K., Tsukayama M., Ohtsuru
(80 mg) at room temperature until uptake of hydrogen ceased. The resulting Y., Chem. Pharm. Bull., 46, 222—230 (1998).
compound was recrystallized from a mixture of water and MeOH to give 3 22) Becker H.-D., “The Chemistry of the Quinoid Compounds, Part 1,” ed.
(367 mg, 92%) as colorless needles, mp 230—232 °C (lit.,7) 225—228 °C);
by Patai S., John Wiley & Sons, London, 1974, pp. 335—423.
1H-NMR (see Table 1). Anal. Calcd for C20H20O6: C, 67.41; H, 5.66. Found: 23) Becker H.-D., Björk A., Adler E., J. Org. Chem., 45, 1596—1600
C, 67.22; H, 5.48.
(1980).
4ꢁ,7-Diacetoxy-5-hydroxy-6-(3-hydroxy-3-methylbutyl)coumarono-