Regioselective synthesis of 6-prenylpolyhydroxyisoflavone (wighteone) and wighteone hydrate with hypervalent iodine

Article abstract of DOI:10.1080/00397910500514121

The oxidative rearrangement of 3′-iodotetraalkoxychalcone with [hydroxyl(tosyloxy)iodo]benzene, followed by cyclization of the resultant acetal gave 6-iodotrialkoxyisoflavone. The coupling reaction of the isoflavone with 2-methyl-3-butyn-2-ol gave 6-alkynylisoflavone, whose hydrogenation gave wighteone hydrate. Wighteone was synthesized by dehydration of wighteone hydrate. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500514121

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Regioselective Synthesis of
6‐Prenylpolyhydroxyisoflavone (Wighteone)
and Wighteone Hydrate with Hypervalent
Iodine
Takanori Tokuoka a , Kazuyo Yamashita a , Yasuhiko Kawamura a , Masao
Tsukayama a & Mohammad M. Hossain a
a Department of Chemical Science and Technology, Faculty of Engineering ,
University of Tokushima , Tokushima, Japan
Published online: 24 Feb 2007.
To cite this article: Takanori Tokuoka , Kazuyo Yamashita , Yasuhiko Kawamura , Masao Tsukayama &
Mohammad M. Hossain (2006) Regioselective Synthesis of 6‐Prenylpolyhydroxyisoflavone (Wighteone) and
Wighteone Hydrate with Hypervalent Iodine, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:9, 1201-1211, DOI: 10.1080/00397910500514121
To link to this article: http://dx.doi.org/10.1080/00397910500514121
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Synthetic Communicationsw, 36: 1201–1211, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500514121
Regioselective Synthesis
of 6-Prenylpolyhydroxyisoflavone
(Wighteone) and Wighteone Hydrate
with Hypervalent Iodine
Mohammad M. Hossain, Takanori Tokuoka,
Kazuyo Yamashita, Yasuhiko Kawamura, and
Masao Tsukayama
Department of Chemical Science and Technology, Faculty of
Engineering, University of Tokushima, Tokushima, Japan
Abstract: The oxidative rearrangement of 30-iodotetraalkoxychalcone with [hydro-
xyl(tosyloxy)iodo]benzene, followed by cyclization of the resultant acetal gave
6-iodotrialkoxyisoflavone. The coupling reaction of the isoflavone with 2-methyl-3-
butyn-2-ol gave 6-alkynylisoflavone, whose hydrogenation gave wighteone hydrate.
Wighteone was synthesized by dehydration of wighteone hydrate.
Keywords: Synthesis, wighteone, 6-prenylisoflavone, 30-iodochalcone, hypervalent
iodine
Isoflavone derivatives are widely distributed in nature and are very important
as precursors of prenylisoflavones and pterocarpans.[1,2] In addition, isofla-
vone derivatives exhibit phytoalexin, antifungal, antiinflammatory, and anti-
cancer properties.[3–5] Hence, isoflavones have attracted considerable
attention in recent years. Wighteone 1, a prenylated isoflavone, was first
isolated from healthy leaves of Lupinus albus together with luteone in 1976,
but its structure was not fully identified at that time.[6] In 1977, wighteone 1
Received in Japan August 25, 2005
Address correspondence to Masao Tsukayama, Department of Chemical Science
and Technology, Faculty of Engineering, University of Tokushima, Tokushima 770-
8506, Japan. E-mail: tukayama@chem.tokushima-u.ac.jp
1201

1202
M. M. Hossain et al.
was isolated from fungus-inoculated stems of Glycine wightii as a phyto-
alexin, and the structure was assigned to be 40,5,7-trihydroxy-6-(3-methyl-2-
butenyl)isoflavone 1 on the basis of spectroscopic data.[3] Wighteone 1 was
also isolated as erythrinin B from the barks of Erythrina vareigata[7] and
from the roots of white lupin together with luteone.[8,9] Wighteone 1 was
also metabolized in a culture of Aspergillus flavus and transformed into
wighteone hydrate 2 as a major metabolite, whose structure was deter-
mined as 40,5,7-trihydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone 2 by
spectroscopic analysis.[10]
The total synthesis of wighteone 1 has yet to be achieved even though it
is an important compound because it shows unique biological activity.[10]
However, the isomer [lupiwighteone ¼ 40,5,7-trihydroxy-8-(3-methyl-2-
butenyl)isoflavone] of wighteone 1 has already been synthesized.[11,12] The
regioselective and direct introduction of alkenyl or alkyl group at the
6-position of isoflavone skeleton is relatively difficult, because it consists
of many protections and consequent deprotections, and the easy isomeriza-
tion of 6-alkylpolyhydroxyisoflavones into 8-alkylpolyhydroxyisoflavones
by bases.[13,14] Generally, isoflavones are synthesized by oxidative rearrange-
.
ment of chalcones with Tl(III)(NO3)3 3H2O, thallium(III) nitrate trihydrate
(TTN).[15,16]
Wighteone hydrate 2 was synthesized by oxidative rearrangement of the
corresponding 30-iodochalcone with TTN in low yield.[17] 5,7-Bis(benzy-
loxy)-6-iodo-30,40-methylenedioxyisoflavone was also obtained by the
oxidative rearrangement of the corresponding chalcone with TTN in low
yield (17%). These results show a limit and scope of TTN as an
oxidative reagent of chalcone. Moreover, TTN is toxic and has adverse
effects on the environment. Recently, it has been reported that hypervalent
iodine reagents such as [hydroxy(tosyloxy)iodo]benzene (HTIB)[18] and
[bis(trifluoroacetoxy) iodo]benzene (BTIB)[19] have become more useful
for the oxidative rearrangement of chalcones. We have achieved better
results by using hypervalent iodine as oxidizing agents for the conversions
of chalcones to acetals and isoflavones.[20] Moreover, unlike TTN, hyper-
valent iodine reagents are environmentally friendly and easy to prepare
and handle.[21] In continuation of our studies on the synthesis of pre-
nylisoflavones, we report here the first total synthesis of wighteone 1 and
wighteone hydrate 2 from the corresponding 30-iodochalcone using
[hydroxy(tosyloxy)iodo]benzene.[21]
RESULTS AND DISCUSSION
The introduction of iodine at the 30-position of 60-methoxymethoxyacetophe-
none 3, obtained by the catalytic hydrogenation (5% Pd/C) of 20,40-bis(benzy-
loxy)-60-methoxymethoxyacetophenone,[14] was carried out with iodine and
periodic acid[17,22] to give the desired 30-iodoacetophenone 4 in 94% yield.

Prenylpolyhydroxyisoflavone (Wighteone) and Wighteone Hydrate
1203
The benzylation of compound 4 with benzyl chloride in the presence
of K2CO3 in dimethyl formamide (DMF) gave 20,40-bis(benzyloxy)-30-iodo-
acetophenone 5 in 82% yield. Condensation of 5 with 4-benzyloxy-
benzaldehyde in the presence of alcoholic KOH solution gave
60-methoxymethoxychalcone 6 (Scheme 1).
60-Hydroxychalcone 7 was obtained in 85% yield from the crude
compound 6 by conc. HCl-mediated hydrolysis in a mixture of methanol
and chloroform (via two steps from 5). A crucial oxidative rearrangement
of 60-benzoyloxychalcone 8, prepared by benzoylation of 7, with HTIB in a
mixture of methanol and chloroform gave the crude acetal 9. The structure
1
of acetal 9 was confirmed by H NMR [d: 3.05 and 3.23, CH(OCH3)2]. The
subsequent hydrolysis of the crude 9 with 20% NaOH and in situ ring
closure afforded the desired 6-iodoisoflavone 10 in 67% yield (via two steps
from 8). The oxidative rearrangement and cyclization methodology is much
easier than the case of that with TTN. The coupling reaction of 10 with
2-methyl-3-butyn-2-ol in the presence of Pd(0)[23] in a mixture of triethyl-
amine and DMF gave 6-(3-hydroxy-3-methylbutynyl)isoflavone 11 in 91%
yield. The quantitative catalytic hydrogenation of 11 with 5% Pd/C in a
mixture of methanol and dioxane afforded 40,5,7-trihydroxy-6-(3-hydroxy-3-
methylbuyl)isoflavone 2 in 88% yield. The spectral data and other physical
properties of 2 were identical with those of the natural sample of wighteone
hydrate[10] (Table 1 and Experimental section). The exhaustive bezoylation
of 2 by bases in prolonged reaction time causes the isomerization of 6-alkyl-
polyhydroxyisoflavone to 8-alkylpolyhydroxyisoflavone.[13,14] Therefore, the
partial benzoylation of 2 was achieved in acetone at 458C for 20 min to give
the 5-hydroxyisoflavone 12 in 85% yield. The tosylation of 12 with p-TsCl
Scheme 1.

Table 1. 1H-NMR (400 MHz, CD3COCD3) data for 6-prenyl- and alkylisoflavones 1, 2, wighteone, and wighteone hydratea
Me
60-H
CH2
50-H
Compound
2-H
8-H
20-H
30-H
CH55C
OH
1
8.14s
(J ¼ 8.7)
8.15s
6.49s
(J ¼ 8.7)
6.49s
7.46d
1.78s
6.90d
(J ¼ 7.1)
6.90br.d
1.65s
(J ¼ 7.1)
1.65s
3.37d
3.37br.d
1.71m
5.28t
13.32s
Natural Product10) (1)
7.45br.d
1.78s
5.28br.t
8.43s
13.32s
(J ¼ 8.8)
8.15s
(J ¼ 8.8)
6.47s
(J ¼ 7.1)
6.91d
2.78m
(J ¼ 7.1)
1.26s
13.32s
2
7.46d
(6H)
(J ¼ 8.7)
8.14s
(J ¼ 8.7)
6.47s
Natural Product10) (2)
7.46br.d
(6H)
6.91br.d
2.78m
1.26s
13.31s
1.71m
(J ¼ 8.8)
(J ¼ 8.8)
as: singlet; d: doublet; t: triplet; br: broad; m: multiplet.

Prenylpolyhydroxyisoflavone (Wighteone) and Wighteone Hydrate
1205
under reflux in acetone for 2 h gave 5-tosylated isoflavone 13 in 84% yield.
.
Compound 13 was dehydrated with TsOH H2O in a solution of acetic acid
and toluene under reflux for 1.5 h to give a mixture of the desired 6-prenyliso-
flavone 14 and the regioisomer, 6-(3-methyl-3-butenyl)isoflavone 16. The 1H
NMR spectrum of the alkenyl mixture (14 and 16) showed the ratio of 14 to 16
to be 74 : 26 [peaks due to CH2CH55C(CH3)2 at d: 3.37 (2H, d) and CH2CH2-
C(CH3)55CH2 at d: 4.51 and 4.62 (each 1H, s)]. The treatment of the mixture
(14 and 16) with benzohydroximoyl chloride[17] in dry dichloromethane at
room temperature gave a mixture of the unchanged 6-pryenylisoflavone 14
and the terminal alkene-cyclic adduct, and then 14 was separated by silica-
gel column chromatography in 57% yield (via two steps from 13). The deto-
sylation of 14 with 1 M BCl3 solution in dichloromethane at room temperature
gave 5-hydroxyisoflavone 15 in 91% yield. The hydrolysis of 15 with 10%
NaOH in a mixture of methanol and dioxane at room temperature gave
40,5,7-trihydroxy-6-(3-methyl-2-butenyl)isoflavone 1 in 72% yield. The
spectral data and other physical properties of 1 were identical with those of
the natural sample of wighteone[10] (Table 1 and Experimental section). On the
basis of these results, the structure of wighteone was confirmed for the
first time by the synthesis of 40,5,7-trihydroxy-6-(3-methyl-2-butenyl)iso-
flavone 1. Synthetic wighteone 1 was converted into 6-prenyltriacetoxy-
isoflavone 17.
EXPERIMENTAL
All the melting points were taken on a Yanaco MP-J3 micro-melting-point
1
apparatus and are uncorrected. The H NMR spectra were recorded with a
JEOL EX-400 spectrophotometer (400 MHz) using tetramethylsilane (TMS)
as internal standard. The IR spectra were obtained on Hitachi 260-10 spectro-
photometer using KBr pellets. The UV spectra were obtained on Hitachi
U-2000 spectrophotometer. Elemental analyses were obtained on Yanaco
CHN corder model MT-5. Column chromatography and thin-layer chromato-
graphy (TLC) were carried out with Kieselgel 60 (70–230 mesh) and
Kieselgel 60 F-254 (Merck).
20,40-Dihydroxy-60-methoxymethoxyacetophenone (3): The palladium-
carbon-catalyzed hydrogenolysis of 20,40-bis(benzyloxy)-60-methoxymethoxy-
acetophenone[14] (4.8 g, 12.24 mmol) in a mixture of MeOH (100 ml) and
AcOEt (100 ml) was carried out at 208C until the uptake of hydrogen
ceased. The solvent was removed under reduced pressure, and the resulting
compound was recrystallized from a mixture of AcOEt and hexane to give
1
3 (2.48 g, 95%) as colorless crystals, mp 117–1198C. H NMR (CDCl3) d:
2.65 (3H, s, COCH3), 3.52 (3H, s, OCH3), 5.25 (2H, s, OCH2O), 6.04 (1H,
0
d, J ¼ 2.4 Hz, Ar-H), 6.14 (1H, d, J ¼ 2.4 Hz, Ar-H), 13.79 (1H, s, C2 -OH);
anal. calcd. for C10H12O5: C, 56.60; H, 5.70; found: C, 56.61; H, 5.60.

1206
M. M. Hossain et al.
20,40-Dihydroxy-30-iodo-60-methoxymethoxyacetophenone (4): Compound
3 (3.75 g, 17.61 mmol) was dissolved in ethanol (80 ml), followed by the suc-
cessive addition of iodine (2.22 g, 8.74 mmol) and periodic acid (806 mg,
3.53 mmol in water, 9 ml). The reaction mixture was stirred for 1 h at 408C.
Cooling and diluting the reaction mixture with water gave a crystalline
solid, which was recrystallized from the mixture of AcOEt and hexane to
give 4 (5.59 g, 94%) as pale yellow needles, mp 162–1648C. 1H NMR
(CDCl3) d: 2.69 (3H, s, COCH3), 3.52 (3H, s, OCH3), 5.28 (2H, s,
0
OCH2O), 5.98 (1H, s, C4 -OH), 6.44 (1H, s, C5 -H), 14.97 (1H, s, C2 -OH);
0
0
anal. calcd. for C10H11IO5: C, 35.52; H, 3.28; found: C, 35.32; H, 3.17.
20,40-Bis(benzyloxy)-30-iodo-60-methoxymethoxyacetophenone (5):
A
solution of benzyl chloride (4.1 g, 32.41 mmol) in DMF (5 ml) was added
slowly to a mixture of 4 (5.0 g, 14.79 mmol) and K2CO3 (10 g, 72.46 mmol)
in DMF (50 ml) under nitrogen. The reaction mixture was heated at 708C for
1 h, then cooled to rt, and extracted with CHCl3. The extract was washed
with 5% HCl and water and dried (Na2SO4), and the solvent was removed.
The residue was recrystallized from a mixture of AcOEt and MeOH to give
1
5 (6.3 g, 82%) as colorless needles, mp 98–998C. H NMR (CDCl3) d: 2.47
(3H, s, COCH3), 3.46 (3H, s, OCH3), 4.97 (2H, s, PhCH2), 5.15 (2H, s,
0
OCH2O), 5.18 (2H, s, PhCH2), 6.65 (1H, s, C5 -H), 7.32–7.6 (10H, m,
Ar-H); anal. calcd. for C24H23IO5: C, 55.61; H, 4.47; found: C, 55.66; H, 4.48.
4,20,40-Tris(benzyloxy)-60-methoxymethoxy-30-iodochalcone
(6)
and
4,20,40-tris(benzyloxy)-60-hydroxy-30-iodochalcone (7): A mixture of 5
(5.0 g, 9.64 mmol) and 4-benzyloxybenzaldehyde (2.66 g, 12.53 mmol) was
.
dissolved in alc KOH (5.40 g, 96.2 mmol in 150 ml of EtOH). The reaction
mixture was refluxed for 1 h and monitored by TLC to establish completion.
The reaction mixture was neutralized with 10% HCl and extracted with
CHCl3, and solvent was removed under reduced pressure to give a yellow
semisolid mass of 60-methoxymethoxychalcone 6, which was hydrolyzed
with conc. HCl in a mixture of MeOH (100 ml) and CHCl3 (100 ml) at
408C for 1 h. The hydrolyzed mixture was allowed to cool to rt, extracted
with CHCl3, washed with water, and dried (Na2SO4). The solvent was
removed under reduced pressure to give a solid mass, which was recrystallized
from CHCl3 and AcOEt to afford 60-hydroxychalcone 7 (5.48 g, 85% two steps
1
yield from 5) as yellow needles, mp 138–1408C. H NMR (CDCl3) d: 4.85,
0
5.10, and 5.21 (each 2H, s, PhCH2), 6.42 (1H, s, C5 -H), 6.82 (2H, d,
J ¼ 8.7 Hz, C3- and C5-H), 7.18–7.52 (17H, m, Ar-H), 7.85 (2H, d,
0
J ¼ 15.4 Hz, CH55CH), 13.77 (1H, s, C6 -OH); anal. calcd. for C36H29IO5:
C, 64.68; H, 4.37; found: C, 64.53; H, 4.54.
4,20,40-Tris(benzyloxy)-60-benzoyloxy-30-iodochalcone
chloride (1.27 g, 9.0 mmol) was slowly added to a mixture of chalcone 7
(6.0 g, 8.98 mmol) and K2CO3 (8.6 g, 62.3 mmol) in DMF (30 ml). The
(8):
Benzoyl

Prenylpolyhydroxyisoflavone (Wighteone) and Wighteone Hydrate
1207
reaction mixture was heated at 60–708C under nitrogen for 30 min and filtered
of K2CO3. Then the filtrate was neutralized with 5% HCl, extracted with
CHCl3, washed with water, and dried (Na2SO4). After removal of the
solvent a pale yellow crude mass was obtained. The crude was purified on
silica-gel column chromatography (CHCl3:hexane 3 : 2) and gave fluffy
1
crystalline solid of 8 (6.1 g, 88%), mp 47–488C. H NMR (CDCl3) d: 4.99,
0
5.07, and 5.21 (each 2H, s, PhCH2), 6.76 (1H, s, C5 -H), 6.88 (2H, d,
J ¼ 15.8 Hz, CH55CH), 6.89 (2H, d, J ¼ 8.7 Hz, C2- and C6-H), 7.27–7.63
(20H, m, Ar-H), 8.03 (2H, d, J ¼ 8.7 Hz, C3- and C5-H); anal. calcd for
C43H33IO6: C, 66.85; H, 4.31; found: C, 66.68; H, 4.45.
1-[6-Benzoyloxy-2,4-bis(benzyloxy)-3-iodophenyl]-2-[4-benzyloxyphe-
nyl]-3,3-dimethoxypropan-1-one (9) and 40,5,7-tris(benzyloxy)-6-iodoiso-
flavone (10): Compound 8 (6.65 g, 8.61 mmol) was dissolved in a mixture
of MeOH (80 ml) and CHCl3 (25 ml) followed by the addition of HTIB
(4.56 g, 11.63 mmol). The reaction mixture was stirred at rt under nitrogen
for 24 h. The excess HTIB was decomposed with 5% Na2SO3 solution
(2 ml), and then the reaction mixture was extracted with CHCl3, washed
with water, and dried (Na2SO4). Removal of the solvent under reduced
pressure gave crude acetal 9 (8.5 g) as a semisolid mass. This crude mass
was dissolved in a mixture of MeOH (60 ml) and CHCl3 (20 ml) followed
by the addition of 20% NaOH (35 ml) and stirred at 258C for 5 h. The
reaction mixture was neutralized with 10% HCl, extracted with CHCl3,
washed with water, and dried (Na2SO4). The solvent was removed under
reduced pressure to give yellow solid. The crude solid was purified by
column chromatography (CH2Cl2:hexane 3 : 1) and further recrystallized
from a mixture of AcOEt and MeOH (1 : 1) to give 6-iodoisoflavone 10
1
(3.82 g, 67%, two steps yield from 8), mp 154–1568C. H NMR (CDCl3) d:
5.07, 5.10, and 5.26 (each 2H, s, PhCH2), 6.74 (1H, s, C8-H), 7.03 (2H, d,
0
0
J ¼ 8.3 Hz, C3 - and C5 -H), 7.31–7.53 (15H, m, Ar-H), 7.77 (2H, d,
0
0
J ¼ 8.5 Hz, C2 - and C6 -H), 7.81 (1H, s, C2-H); anal. calcd for C36H27IO5:
C, 64.87; H, 4.08; found: C, 64.65; H, 4.22.
Acetal 9: 1H NMR (CDCl3) d: 3.05 and 3.23 (each 3H, s, OCH3), 4.92, 4.98,
and 5.11 (each 2H, s, PhCH2), 4.78 and 4.95 (each 1H, d, J ¼ 10.2 Hz, CH),
0
0
6.59 (1H, s, C8-H), 7.05 (2H, d, J ¼ 8.7 Hz, C3 - and C5 -H), 7.11 (2H, d,
0
0
J ¼ 8.6 Hz, C2 - and C6 -H), 7.15–7.71 (24H, m, Ar-H).
40,5,7-Tris(benzyloxy)-6-(3-hydroxy-3-methyl-1-butynyl)isoflavone (11):
Compound 10 (3.0 g, 4.49 mmol) was dissolved in DMF (15 ml) followed
by the successive addition of Et3N (70 ml), PdCl2 (41 mg, 0.23 mmol),
PPh3 (120 mg, 0.45 mmol), CuI (44 mg, 0.23 mmol), and finally 2-methyl-3-
butyn-2-ol (1.3 ml, 13.5 mmol). The reaction mixture was heated at 808C
under nitrogen for 2 h and then cooled to rt. The cool mixture was filtered
through sintered glass using celite, and the filtrate was extracted with

1208
M. M. Hossain et al.
AcOEt, washed with 5% HCl and water, and dried (Na2SO4). The solvent was
removed under reduced pressure, and the resulting solid was chromatographed
on silica-gel column (CH2Cl2:AcOEt 9 : 1) and further recrystallized from
AcOEt and Me2CO (2 : 1) to give 11 as a colorless crystalline solid (2.54 g,
1
91%), mp 170–1718C. H NMR (CDCl3) d: 1.50 and 1.54 (each 3H, s,
CH3), 5.10 (2H, s, PhCH2), 5.20 (4H, s, PhCH2 ꢀ 2), 6.71 (1H, s, C8-H),
0
0
0
7.04 (2H, d, J ¼ 8.7 Hz, C3 - and C5 -H), 7.68 (2H, d, J ¼ 8.3 Hz, C2 - and
0
C6 -H), 7.29–7.52 (15H, m, Ar-H), 7.79 (1H, s, C2-H); anal. calcd. for
C41H34O6: C, 79.08; H, 5.50; found: C, 79.11; H, 5.68.
40,5,7-Trihydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone (wighteone hy-
drate) (2): Compound 11 (1.0 g, 1.6 mmol) was hydrogenolyzed over 5%
Pd/C (120 mg) in a mixture of methanol (35 ml) and dioxane (35 ml) until
the uptake of hydrogen ceased. The resulting compound was recrystallized
from MeOH and Me2CO to give 2 (504 mg, 88%) as colorless solid, mp
230–2328C (lit.[10] 225–2288C). 1H NMR (Table 1); IR (KBr) n 3340,
3300, 2920, 1620, 1500, 1450, 1220, 1058 cm21; UV lmax nm (log 1)
(MeOH): 265sh (4.41), 214 (4.29), (þAlCl3) 269 (4.37), (þNaOAc) 335.5
(4.1), 274.5sh (4.39), 231sh (4.45); anal. calcd. for C20H20O6: C, 67.41; H,
5.66; found: C, 67.36; H, 5.80.
40,7-Bis(benzoyloxy)-5-hydroxy-6-(3-hydroxy-3-methylbutyl)isoflavone
(12): A mixture of 2 (650 mg, 1.82 mmol), benzoyl chloride (0.48 ml,
4.13 mmol), and K2CO3 (1.4 g, 10.14 mmol) in acetone (25 ml) was heated
at 458C under nitrogen for 25 min. Filtering off K2CO3 and removing the
solvent under reduced pressure gave a residue, which was extracted with
AcOEt, washed with 5% HCl and water, and dried (Na2SO4). The solvent
was removed under reduced pressure, and the resulting compound was recrys-
tallized from a mixture of CH2Cl2 and Me2CO to give 12 (880 mg, 85%) as
colorless needles, mp 160–1618C. 1H NMR (CDCl3) d: 1.20 (6H, s,
CH3 ꢀ 2), 1.74 and 2.77 (each 2H, m, CH2), 6.90 (1H, s, C8-H), 7.34 (2H,
0
0
d, J ¼ 8.5 Hz, C3 - and C5 -H), 7.25–7.68 (10H, m, Ar-H), 8.01 (1H, s, C2-H),
0
0
0
8.24 (2H, d, J ¼ 8.5 Hz, C2 - and C6 -H, Ar-H); 13.13 (1H, s, C5 -OH); anal.
calcd. for C34H28O8: C, 72.33; H, 5.00; found: C, 72.45; H, 5.10.
40,7-Bis(benzoyloxy)-6-(3-hydroxy-3-methylbutyl)-5-tosyloxyisoflavone
(13): A mixture of 12 (860 mg, 1.52 mmol), tosyl chloride (498 mg,
2.61 mmol), and K2CO3 (2.1 g, 15.2 mmol) in acetone (40 ml) was
refluxed under nitrogen for 2 h. The reaction mixture was cooled to rt, neu-
tralized with 5% HCl, extracted with AcOEt, washed with water, and dried
(Na2SO4). After removal of the solvent, the obtained crude solid was recrys-
tallized from a mixture of CHCl3 and Me2CO (10 : 3) to give 13 (925 mg,
84%) as colorless needles, mp 178–1818C. 1H NMR (CDCl3) d: 1.14
(6H, s, CH3 ꢀ 2), 1.33 (1H, br.s, OH), 1.74 and 2.82 (each 2H, m, CH2),
2.42 (3H, s, Ar-CH3), 7.25–7.74 (15H, m, Ar-H), 7.90 (1H, s, C2-H),

Prenylpolyhydroxyisoflavone (Wighteone) and Wighteone Hydrate
1209
0
0
0
7.96 (2H, d, J ¼ 8.5 Hz, C3 - and C5 -H), 8.23 (2H, d, J ¼ 8.5 Hz, C2 - and
0
C6 -H, Ar-H); anal. calcd. for C41H34O10S; C, 68.51; H, 4.77; found: C,
68.75; H, 4.81.
40,7-Bis(benzoyloxy)-6-(3-methyl-2-butenyl)-5-tosyloxyisoflavone
To a solution of 13 (1.0 g, 1.4 mmol) in dry toluene (10 ml) was added
(14):
p-TsOH H2O (2.4 ml of a 5.24 ꢀ 1021 M solution in acetic acid). The
.
reaction mixture was refluxed under nitrogen for 90 min. After cooling, the
reaction mixture was extracted with ether, washed with 5% NaHCO3 and
water, and dried (Na2SO4). After removal of the solvent, the obtained crude
was chromatographed on a silica-gel column (CHCl3 as a solvent) to give
1
6-alkenylisoflavone (748 mg) as crystalline solid. The H NMR spectrum
showed that it was a mixture of 6-(3-methyl-2-butenyl)isoflavone 14 and
the regioisomer, 6-(3-methyl-3-butenyl)isoflavone 16 (14 : 16 ¼ 74 : 26).
The mixture was dissolved in CH2Cl2 (4 ml) followed by the careful
addition of benzohydroximoyl chloride (133 mg, 0.86 mmol) and Et3N
(0.2 ml, 1.42 mmol) in an ice bath. The reaction mixture was then stirred at
258C under nitrogen for 8 h. The mixture was quenched with aqueous
NH4Cl and extracted with CH2Cl2, washed with water, and dried (Na2SO4).
The resulting compound was chromatographed on a silica-gel column
(CHCl3:Me2CO 15 : 1) to give the 6-prenylisoflavone 14, which was recrystal-
lized from a mixture of CHCl3 and Me2CO (5 : 1) to give 14 (554 mg, 57%
1
from 13) as a crystalline solid, mp 202–2048C. H NMR (CDCl3) d: 1.41
and 1.46 (each 3H, s, CH3), 2.40 (3H, s, Ar-CH3), 3.36 (2H, d, J ¼ 6.5 Hz,
CH2), 4.96 (1H, t, J ¼ 6.5 Hz,55CH), 7.25–7.70 (13H, m, Ar-H), 7.89 (1H,
s, C2-H), 7.92–8.25 (6H, m, Ar-H); anal. calcd. for C41H32O9S; C, 70.27;
H, 4.60; found: C, 70.05; H, 4.72.
40,7-Bis(benzoyloxy)-5-hydroxy-6-(3-methyl-2-butenyl)isoflavone
(15):
Compound 14 (400 mg, 0.57 mmol) was dissolved in dry CH2Cl2 (10 ml),
followed by the addition of BCl3 (0.58 ml, 1 M solution in CH2Cl2) in an
ice bath. The reaction mixture was stirred at 20–258C under nitrogen for
2.5 h. The resulting mixture was quenched with saturated NH4Cl solution,
extracted with CH2Cl2, washed with water, and dried (Na2SO4). The solvent
was removed under reduced pressure, and the obtained compound was
purified on a silica-gel column (CHCl3 as a solvent) and further recrystallized
from AcOEt to give 15 (285 mg, 91%) as colorless crystalline solid, mp 192–
1
1948C. H NMR (CDCl3) d: 1.58 and 1.60 (each 3H, s, CH3), 3.39 (2H, d,
J ¼ 6.8 Hz, CH2), 5.17 (1H, t, J ¼ 6.8 Hz, 55CH), 6.87 (1H, s, C8-H),
7.32–7.67 (10H, m, Ar-H), 8.00 (1H, s, C2-H), 8.20–8.24 (4H, m, Ar-H),
13.10 (1H, s, C5-OH); anal. calcd. for C34H26O7; C, 74.71; H, 4.79; found:
C, 74.57; H, 4.91.
40,5,7-Trihydroxy-6-(3-methyl-2-butenyl)isoflavone (wighteone) (1):
Compound 15 (180 mg, 0.32 mmol) was dissolved in a mixture of methanol

1210
M. M. Hossain et al.
(3 ml) and dioxane (3 ml) followed by the addition of 10% NaOH (2.0 ml,
5.0 mmol). The reaction mixture was stirred at 258C for 20 min. The
resulting mixture was neutralized with 2% HCl, and the organic layer was
evaporated under reduced pressure. The obtained residue was extracted with
AcOEt, washed with water, and dried (Na2SO4). The solvent was removed
under reduced pressure to give a solid mass, which was chromatographed
on a silica-gel column (AcOEt : CHCl3; 1 : 6), and the resulting compound
was recrystallized from a mixture of CHCl3 and EtOAc to give the targeted
6-prenylisoflavone 1 (80 mg, 72%) as a pale yellow crystalline solid, mp
205–2078C (lit.[10] 206–2088C). 1H NMR (Table 1); IR (KBr) n 3365,
3240br., 2930, 1650, 1615, 1510, 1215, 1065, 818 cm21; UV lmax nm (log 1)
(MeOH): 266sh (4.45), 214 (4.38), (þAlCl3) 268.5sh (4.41), (þNaOAc)
341 (3.93), 275.5 (4.43), 229sh (4.70); anal. calcd. for C20H18O5; C, 70.99;
H, 5.36; found: C, 70.88; H, 5.52.
40,5,7-Triacetoxy-6-(3-methyl-2-butenyl)isoflavone (17): Acetylation of 1
(40 mg, 0.11 mmol) was achieved by the acetic anhydride–pyridine method
at 1108C for 2 h. The obtained gummy mass was chromatographed on a
1
silica-gel column (CHCl3:hexane 5 : 1) to give 17 in 71% yield. H NMR
(CDCl3) d: 1.67 and 1.75 (each 3H, s, CH3), 2.31, 2.35, and 2.43 (each 3H,
s, COCH3), 3.32 (2H, br.d, CH2), 5.01 (1H, br.t, 55CH), 7.12–7.26 (5H, m,
Ar-H), 7.86 (1H, s, C2-H).
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