Synthesis of α-methyldeoxybenzoins

Article abstract of DOI:10.1039/a904946k

Reduction of hydroxy and/or methoxy-substituted isoflavones using LiAlH₄ in refluxing THF provides an easy access to a number of α-methyldeoxybenzoins, possible metabolites of phytoestrogens in man. The synthesis of O-demethylangolensin 2b, 6′-hydroxyangolensin 2c, angolensin 2d, 1-(2,4-dihydroxyphenyl)-2-phenylpropan-1-one 2e, 1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)propan-1-one2f, 4′-O-methylangolensin 2g, 1-(2-hydroxy-4-methoxyphenyl)-2-phenylpropan-1-one 2h, and 1-(2-hydroxyphenyl)-2-phenylpropan-1-one 2i is described. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a904946k

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Synthesis of ꢀ-methyldeoxybenzoins
A. Salakka and K. Wähälä*
Laboratory of Organic Chemistry, Department of Chemistry, PO Box 55, FIN-00014,
University of Helsinki, Finland. E-mail: Kristiina.Wahala@helsinki.fi
Received (in Cambridge, UK) 21st June 1999, Accepted 30th July 1999
Reduction of hydroxy and/or methoxy-substituted isoflavones using LiAlH4 in refluxing THF provides an easy
access to a number of α-methyldeoxybenzoins, possible metabolites of phytoestrogens in man. The synthesis of
O-demethylangolensin 2b, 6Ј-hydroxyangolensin 2c, angolensin 2d, 1-(2,4-dihydroxyphenyl)-2-phenylpropan-1-one
2e, 1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)propan-1-one 2f, 4Ј-O-methylangolensin 2g, 1-(2-hydroxy-4-
methoxyphenyl)-2-phenylpropan-1-one 2h, and 1-(2-hydroxyphenyl)-2-phenylpropan-1-one 2i is described.
Recently, it has been established that α-methyldeoxybenzoins
are likely metabolites of naturally occurring isoflavones such as
genistein 1a, daidzein 1b, biochanin A 1c and formononetin 1d.
The α-methyldeoxybenzoins as such are rare in the plant king-
dom. The sole known example is angolensin 2d which occurs in
the heartwood of Pterocarpus angolensis, in P. indicana and in
Afromosia species.1–5 Angolensin methyl1,2 and cadinyl (sesqui-
terpenoid) ethers1,2 are also known to occur naturally.
Interest in the metabolism of the dietary isoflavones in man is
now rapidly increasing. It is now known that formononetin 1d
is first converted to daidzein 1b and thence to O-demethyl-
angolensin (ODMA, 2b),6 a member of the α-methyldeoxy-
benzoin group of compounds. ODMA 2b was first identified
from the urine and plasma of sheep7–9 and cattle.6,9 Later it was
isolated from the urine of chimpanzees10 and humans,11–13
human plasma,14,15 human faeces,16,17 and from cow milk.18
Angolensin 2d, the methylated analog of ODMA, has been
found only in the urine of sheep.19 The tentative identification
of a new α-methyldeoxybenzoin, 6Ј-hydroxy-O-demethylango-
lensin 2a, in human urine was recently announced.20,21 We have
since confirmed this by comparison with an authentic synthetic
sample.22
also been reported.30 However, there are no mentions of hydride
reductions of unprotected hydroxy-substituted isoflavones in
the literature. The co-occurrence of α-methyldeoxybenzoins
with various isoflavonoid derivatives, and their origin as
reduced metabolites of the latter, prompted us to study the syn-
thesis of α-methyldeoxybenzoins directly from isoflavone start-
ing materials by reduction. This would be highly expedient as
we already have an easy and general access to a number of
isoflavones by a one-pot reaction.31,32 Following our prelimin-
ary report of the first synthesis of 6Ј-hydroxy-O-demethyl-
angolensin 2a, by reduction of genistein with LiAlH4 in
refluxing THF,33 we now describe an improved synthetic path-
way and spectroscopic details for angolensin 2d, O-demethyl-
angolensin 2b and for seven additional α-methyldeoxybenzoins,
many of them new (Table 1) (see Scheme 1).
Known syntheses of α-methyldeoxybenzoins mostly
encompass numerous steps giving poor overall yields, as, for
example, in the synthesis of 4Љ-hydroxy-2Ј,4Ј-dimethoxy-α-
methyldeoxybenzoin by an 8-step route involving the photolysis
of an α-hydroxydihydrochalcone.5 Similarly, there is a multistep
route to angolensin and ODMA by way of a Friedel–Crafts
reaction of 1,3-dimethoxybenzene and 2-methoxypropionic
acid.11,23 More recently, α-methyldeoxybenzoins have been
prepared by a base-catalysed C-methylation of deoxybenzoins,
giving angolensin and its methylated analogs.24 A free OH at
C-2Ј is compatible whereas a 4Ј-OH is methylated. Our experi-
ence is that 2Ј,4Ј-dihydroxydeoxybenzoins give complex mix-
tures of products, also by 4Ј- and α,α-dialkylation, with various
procedures under basic conditions.25
O-Methylated and -benzylated analogs of angolensin have
been prepared directly from angolensin by methylation1,26,27 or
benzylation.1
Certain reductions of isoflavones are reported to furnish
α-methyldeoxybenzoins. Catalytic hydrogenation of the
unsubstituted isoflavone in basic medium leads mainly to 2Ј-
hydroxy-α-methyldeoxybenzoin presumably via the ring-
opened α-methylene derivate.28 Also, Birch reduction using lith-
ium in liquid ammonia converts protected isoflavones to the
corresponding α-methyldeoxybenzoins.29 Some reductions of
protected isoflavones with LiAlH4 giving ring-opened ketones
and further α-methyldeoxybenzoins as minor products have
Scheme 1 Reduction of isoflavones with LiAlH4.
J. Chem. Soc., Perkin Trans. 1, 1999, 2601–2604
This journal is © The Royal Society of Chemistry 1999
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Scheme 2 Suggested reaction pathways for the LAH reduction of isoflavones.
Table 1 Reduction of isoflavones with LiAlH4 in refluxing THF
As the situation is somewhat different with the 7-H or 7-MeO
analogs 1,2-attack at the propenone carbonyl predominates.
Amount of
LiAlH4 (mol
equiv.)
Reaction
time
(t/h)
Starting
material
Yield
(%)
Products
Experimental
Mps were determined in open capillary tubes with an Electro-
thermal apparatus and are uncorrected. IR spectra were
recorded from KBr discs on a FTIR Biorad FTS-7 instrument.
UV spectra were recorded in 94% ethanol solution with a
CARY 5E UV-VIS-NIR spectrophotometer. 1H and 13C NMR
spectra were recorded on a Varian GEMINI-200 FT NMR
1a
1b
1c
1d
1e
1f
5.5
5.5
4.3
3.3
3.3
3.3
2.5
24
1
2
1.5
1.5
2a33
2b
66
42
70
42
60
34
17
50
27
50
29
48
27
2ca
2d
2ea
2fa
3da
3aa
2g
1
spectrometer using the standard H/13C dual probe (chemical
1g
1h
1i
2.5
2.5
2.5
0.25
0.25
0.25
shifts in ppm). J-Values are given in Hz. LR and HR mass
spectra were obtained with a JEOL JMS SX102 mass spec-
trometer operating at 70 eV. TLC was conducted on Merck
silica gel 60 F254 plates, and Merck silica gel 60 (0.040–0.063
mm, 230–400 mesh) was used for flash chromatography. Tetra-
hydrofuran (THF) was dried by distilling over CaH2 before use.
3ba
2h
3ca
2i
a New compound.
General procedure
In Table 1 there are collected the starting isoflavone 1a–i, the
amount of reducing agent used and the reaction time needed
for the completion of reduction is judged by TLC monitoring.
A solution of an isoflavone 1 (0.2 g) in THF (10 cm3) was added
over 0.5 h to a stirred slurry of lithium aluminium hydride (2.5–
5.5 mol equiv., see Table 1) in refluxing THF (5 cm3). After
further refluxing (see Table 1), the reaction mixture was cooled
and poured into saturated aq. NH4Cl at 0 ЊC. The mixture was
neutralized with 2 M HCl and extracted with EtOAc. The
extract was washed with water, dried over Na2SO4 and evapor-
ated. The residue was purified by flash chromatography.
Results and discussion
As seen in the Table, the amount of reagent used was adjusted
to take into account the number of free OH groups. It is also
clearly seen how an increasing number of free OH groups
requires a longer reaction time (in refluxing THF), presumably
due to a combination of electronic and solubility effects.
The α-methyldeoxybenzoins are formed without compli-
cations except when there is no hydroxy substituent at the
isoflavone 7-position. In such cases prop-2-en-1-ols are the
main products. For example, the reduction of 4Ј,7-dimethoxy-
isoflavone 1g gives 1-(2-hydroxy-4-methoxyphenyl)-2-(4-meth-
oxyphenyl)prop-2-en-1-ol 3a and 4Ј-O-methylangolensin 2g in
a ratio of 2 to 1. Contrary to some earlier proposals,28 we
assume that the initial step in these reductions is a 1,4-addition
to the enone system, driven by the 4-oxypyrylium contributor
(A) to the isoflavone structure. This is then followed by ring
opening to a prop-2-en-1-one, in turn reduced by another 1,4-
addition to give the deoxybenzoin enolates, or by a 1,2-addition
to give the propenols (Scheme 2). We suggest that the effect
of the 7-hydroxy substituent is to provide a further resonance
contributor (B) where the propenone carbonyl is lacking, thus
favouring conjugate hydride attack at the propene terminus.
O-Demethylangolensin 2b, 1-(2,4-dihydroxyphenyl)-2-(4-hydroxy-
phenyl)propan-1-one
Flash chromatography eluent: n-hexane–acetone (1:1). White
crystals, mp 101 ЊC (from n-hexane–diethyl ether) (lit.,34
103 ЊC); λmax(EtOH)/nm 214 (ε/dm3 molϪ1 cmϪ1 21 700), 278
(15 300) and 318 (9600); νmax/cmϪ1 3303 (OH) and 1631 (CO);
δH([2H6]acetone) 1.43 (3H, d, J 6.8, 3-H3), 4.76 (1H, q, J 6.8,
2-H), 6.30 (1H, d, J 2.4, 3Ј-H), 6.37 (1H, dd, J 2.4 and 8.6,
5Ј-H), 6.78 (2H, d, J 8.6, 3Љ- and 5Љ-H), 7.20 (2H, d, J 8.5, 2Љ-H
and 6Љ-H) and 7.89 (1H, d, J 8.8, 6Ј-H); δC([2H6]acetone) 18.1
2602
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(C-3), 44.8 (C-2), 102.3 (C-3Ј), 107.3 (C-5Ј), 111.6 (C-1Ј), 115.1
(C-3Љ and -5Љ), 128.1 (C-2Љ and -6Љ), 132.3 (C-1Љ), 132.7 (C-6Ј),
155.8 (C-4Љ), 164.0 (C-2Ј), 165.6 (C-4Ј) and 204.8 (C-1); m/z 258
(Mϩ, 14%), 138 (8), 137 (100) and 121 (17) (Found: Mϩ,
258.0894. C15H14O4 requires M, 258.0892).
4Ј-O-Methylangolensin 2g, 1-(2-hydroxy-4-methoxyphenyl)-2-
(4-methoxyphenyl)propan-1-one
Flash chromatography eluent: n-hexane–acetone (7:4). White
crystals, mp 67 ЊC (from n-hexane–Et2O) (lit.,24 69–70 ЊC);
λmax(EtOH)/nm 215 (ε/dm3 molϪ1 cmϪ1 25 500), 227s (18 700),
276 (18 400) and 319 (11 000); νmax/cmϪ1 3439 (OH) and 1637
(CO); δH(CDCl3) 1.50 (3H, d, J 6.8, 3-H3), 3.75 (3H, s, 4Љ-
OCH3), 3.78 (3H, s, 4Ј-OCH3), 4.59 (1H, q, J 7.0, 2-H), 6.33
(1H, dd, J 8.8 and 2.5, 5Ј-H), 6.38 (1H, d, J 2.3, 3Ј-H), 6.84
(2H, d, J 8.8, 3Љ- and 5Љ-H), 7.21 (2H, d, J 8.8, 2Љ- and 6Љ-H) and
7.69 (1H, d, J 8.8, 6Ј-H); δC(CDCl3) 19.2 (C-3), 46.0 (C-2), 55.2
(OCH3), 55.5 (OCH3), 101.0 (C-3Ј), 107.6 (C-5Ј), 112.7 (C-1Ј),
114.3 (C-3Љ and -5Љ), 128.5 (C-2Љ and -6Љ), 131.9 (C-6Ј), 133.5
(C-1Љ), 158.5 (C-4Љ), 165.8 (C-2Ј), 166.1 (C-4Ј) and 204.9 (C-1);
m/z 286 (Mϩ, 30%), 284 (15), 269 (10), 151 (100), and 135 (40)
(Found: Mϩ, 286.1202. C17H18O4 requires M, 286.1205).
6Ј-Hydroxyangolensin 2c, 2-(4-methoxyphenyl)-1-(2,4,6-tri-
hydroxyphenyl)propan-1-one
Flash chromatography eluent: n-hexane–acetone (1:1). White
crystals, mp 107 ЊC (from benzene); λmax(EtOH)/nm 225 (ε/dm3
molϪ1 cmϪ1 11 500) and 294 (11 100); νmax/cmϪ1 3347 (OH) and
1630 (CO); δH([2H6]acetone) 1.40 (3H, d, J 7.0, 3-H3), 3.73 (3H,
s, OCH3), 5.27 (1H, q, J 6.9, 2-H), 5.89 (2H, s, 3Ј- and 5Ј-H), 6.8
(2H, d, J 8.8, 3Љ-H and 5Љ-H) and 7.23 (2H, d, J 8.8, 2Љ-H and
6ЉH); δC([2H6]acetone) 19.9 (C-3), 49.4 (C-2), 55.3 (OCH3), 96.0
(C-3Ј and -5Ј), 104.8 (C-1Ј), 114.4 (C-3Љ and -5Љ), 130.0 (C-2Љ
and -6Љ), 135.3 (C-1Љ), 159.3 (C-4Љ), 165.3 (C-2Ј, -4Ј and -6Ј) and
207.1 (C-1); m/z 288 (Mϩ, 18%), 270 (5), 167 (6), 153 (100)
and 135 (45) (Found: Mϩ, 288.1000. C16H16O5 requires M,
288.0998).
1-(2-Hydroxy-4-methoxyphenyl)-2-phenylpropan-1-one 2h
Flash chromatography eluent: n-hexane–acetone (7:4). White
crystals, mp 109 ЊC (from n-hexane) (lit.,29 108 ЊC); λmax(EtOH)/
nm 213 (ε/dm3 molϪ1 cmϪ1 18 100), 280 (13 300), 231 (7770) and
318 (7570); νmax/cmϪ1 3428 (OH) and 1630 (CO); δH(CDCl3)
1.53 (3H, d, J 7.0, 3-H3), 3.79 (3H, s, 4Ј-OCH3), 4.64 (1H, q,
J 6.8, 2-H), 6.32 (1H, dd, J 2.6 and 8.8, 5Ј-H), 6.39 (1H, d, J 2.4,
3Ј-H), 7.19–7.32 (5H, m, Ar-H) and 7.69 (1H, d, J 8.8, 6Ј-H);
δC(CDCl3) 19.2 (C-3), 47.0 (C-2), 55.6 (OMe), 101.1 (C-3Ј),
107.7 (C-5Ј), 112.8 (C-1Ј), 127.1 (C-4Љ), 127.6 (C-2Љ and -6Љ),
129.1 (C-3Љ and -5Љ), 132.1 (C-6Ј), 141.6 (C-1Љ), 165.9 (C-2Ј),
166.2 (C-4Ј) and 204.7 (C-1); m/z 256 (Mϩ, 7%), 162 (5), 152
(10), 151 (100), 117 (10) and 58 (40) (Found: Mϩ, 256.1090.
C16H16O3 requires M, 256.1099).
Angolensin 2d, 1-(2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)-
propan-1-one
Flash chromatography eluent: CH2Cl2–EtOAc (7:1). Pale
yellowish crystals, mp 84 ЊC (from benzene) (lit.,24 86–87 ЊC);
λmax(EtOH)/nm 215 (ε/dm3 molϪ1 cmϪ1 37 400), 280 (26 800) and
319 (17 000); νmax/cmϪ1 3353 (OH) and 1630 (CO); δH(CDCl3)
1.49 (3H, d, J 7.0, 3-H3), 3.75 (3H, s, 4Љ-OMe), 4.57 (1H, q,
J 6.8, 2-H), 6.27 (1H, d J 2.5, 3Ј-H), 6.32 (1H, dd, J 2.6 and
8.8, 5Ј-H), 6.84 (2H, d, J 8.6, 3Љ- and 5Љ-H), 7.20 (2H, d,
J 8.7, 2Љ- and 6Љ-H), 7.68 (1H, d, J 8.8, 6Ј-H) and 12.00 (1H,
br s, OH); δC(CDCl3) 19.2 (C-3), 45.9 (C-2), 55.3 (OMe),
103.5 (C-3Ј), 108.1 (C-5Ј), 112.8 (C-1Ј), 114.4 (C-3Љ and -5Љ),
128.6 (C-2Љ and -6Љ), 132.8 (C-6Ј), 133.5 (C-1Љ), 158.4 (C-4Љ),
162.8 (C-2Ј), 165.6 (C-4Ј) and 205.4 (C-1); m/z 272 (Mϩ,
36%), 151 (5), 149 (5), 138 (17), 137 (100), 136 (15), 135 (60),
105 (5) and 91 (5) (Found: Mϩ, 272.1047. C16H16O4 requires
M, 272.1048).
1-(2-Hydroxyphenyl)-2-phenylpropan-1-one 2i
Flash chromatography eluent: n-hexane–acetone (7:4). Color-
less oil; λmax(EtOH)/nm 213 (ε/dmϪ3 molϪ1 cmϪ1 19 100), 255
(9140) and 329 (4050); νmax/cmϪ1 2978 (OH) and 1638 (CO);
δH(CDCl3) 1.54 (3H, d, J 7.0, 3-H3), 4.73 (1H, q, J 6.6, 2-H),
6.78 (1H, t, J 8.3, 5Ј-H), 6.94 (1H, d, J 7.4, 3Ј-H), 7.19–7.42 (6H,
m, Ar-H) and 7.79 (1H, d, J 8.0, 6Ј-H); δC(CDCl3) 19.3 (C-3),
47.3 (C-2), 118.7 (C-1Ј and -3Ј), 118.9 (C-5Ј), 127.2 (C-4Љ), 127.6
(C-2Љ and -6Љ), 129.1 (C-3Љ and -5Љ), 130.5 (C-6Ј), 136.2 (C-4Ј),
141.2 (C-1Љ), 163.2 (C-2Ј) and 206.6 (C-1); m/z 226 (Mϩ, 11%),
194 (5), 122 (8), 121 (100), 105 (12), 77 (7) and 58 (35) (Found:
Mϩ, 226.0996. C15H14O2 requires M, 226.0994).
1-(2,4-Dihydroxyphenyl)-2-phenylpropan-1-one 2e
Flash chromatography eluent: CH2Cl2–EtOAc (7:2). White
crystals, mp 137 ЊC (from n-hexane–Et2O); λmax(EtOH)/nm 213
(ε/dm3 molϪ1 cmϪ1 22 200), 282 (15 300), 234 (8650) and 317
(9540); νmax/cmϪ1 3357 (OH) and 1631 (CO); δH([2H6]acetone)
1.48 (3H, d, J 6.8, 3-H3), 4.88 (1H, q, J 6.6, 2-H), 6.30 (1H, d,
J 2.2, 3Ј-H), 6.36 (1H, dd, J 2.4 and 8.8, 5Ј-H), 7.16–7.43 (5H,
m, Ar-H) and 7.90 (1H, d, J 9.0, 6Ј-H); δC([2H6]acetone) 19.5
(C-3), 47.1 (C-2), 103.7 (C-3Ј), 108.8 (C-5Ј), 113.1 (C-1Ј), 127.8
(C-4Љ), 128.5 (C-2Љ and -6Љ), 129.8 (C-3Љ and -5Љ), 134.1 (C-6Ј),
143.1 (C-1Љ), 165.5 (C-2Ј), 167.1 (C-4Ј) and 205.8 (C-1); m/z 242
(Mϩ, 12%), 138 (10), 137 (100), 105 (13), 77 (5) and 58 (46)
(Found: Mϩ, 242.0944. C15H14O3 requires M, 242.0943).
1-(2-Hydroxy-4-methoxyphenyl)-2-(4-methoxyphenyl)prop-2-en-
1-ol 3a
Flash chromatography eluent: n-hexane–acetone (7:4). Amor-
phous solid; λmax(EtOH)/nm 205 (ε/dmϪ3 molϪ1 cmϪ1 13 100)
and 254 (5130); νmax/cmϪ1 3350 (OH); δH(CDCl3) 3.70 (3H, s,
OCH3), 3.75 (3H, s, OCH3), 5.21 (1H, s, 3-H), 5.43 (1H, s, 3-H),
5.80 (1H, s, 1-H), 6.32 (1H, dd, J 8.4 and 2.4, 5Ј-H), 6.41 (1H, d,
J 2.4, 3Ј-H), 6.78–6.86 (3H, m, 6Ј-, 3Љ- and 5Љ-H), 7.30 (2H, d,
J 6.7, 2Љ- and 6Љ-H) and 7.97 (1H, br s, OH); δC(CDCl3) 55.2
(2 × OCH3), 75.4 (C-1), 102.4 (C-3), 105.8 (C-3Ј), 113.6 (C-5Ј),
113.9 (C-3Љ and -5Љ), 117.6 (C-1Ј), 128.1 (C-2Љ and -6Љ), 129.2
(C-6Ј), 131.0 (C-1Љ), 148.0 (C-2), 156.9 (C-2Ј), 159.2 (C-4Ј) and
160.5 (C-4Љ); m/z 286 (Mϩ, 2%), 282 (20), 269 (18), 268 (100,
Mϩ Ϫ 18), 267 (80), 253 (21), 239 (10), 224 (8), 153 (17) and 134
(10) (Found: Mϩ, 286.1219. C17H18O4 requires M, 286.1176).
1-(2-Hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)propan-1-
one 2f
Flash chromatography eluent: n-hexane–acetone (1:1). White
crystals, mp 142 ЊC (from n-hexane–diethyl ether); λmax(EtOH)/
nm 214 (ε/dm3 molϪ1 cmϪ1 24 800), 227s (17 600), 276 (18 100)
and 320 (10 400); νmax/cmϪ1 3465 (OH) and 1629 (CO); δH([2H6]-
acetone) 1.43 (3H, d, J 6.8, 3-H3), 3.83 (3H, s, OCH3), 4.79 (1H,
q, J 6.9, 2-H), 6.38 (1H, d, J 2.6, 3Ј-H), 6.41 (1H, dd, J 8.2 and
2.6, 5Ј-H), 6.78 (2H, d, J 8.6, 3Љ- and 5Љ-H), 7.20 (2H, d, J 8,6,
2Љ- and 6Љ-H) and 7.94 (1H, d, J 8.3, 6Ј-H); δC([2H6]acetone)
19.5 (C-3), 46.4 (C-2), 56.1 (OCH3), 101.8 (C-3Ј), 108.1 (C-5Ј),
115.2 (C-1Ј), 116.7 (C-3Љ and -5Љ), 129.6 (C-2Љ and -6Љ), 133.7
(C-6Ј), 134.2 (C-1Љ), 157.5 (C-4Љ), 167.1 (C-2Ј and -4Ј) and 207.1
(C-1); m/z 272 (Mϩ, 18%), 152 (15), 151 (100), 137 (14), 135 (8),
121 (8) (Found: Mϩ, 272.1052. C16H16O4 requires M, 272.1048).
1-(2-Hydroxy-4-methoxyphenyl)-2-phenylprop-2-en-1-ol 3b
Flash chromatography eluent: n-hexane–acetone (7:4). Amor-
phous solid. λmax(EtOH)/nm 205 (ε/dm3 molϪ1 cmϪ1 27 300),
236 (10 200) and 282 (2670); νmax/cmϪ1 3449 (OH) and 3146
(OH); δH(CDCl3) 3.72 (3H, s, 4Ј-OCH3), 5.31 (1H, s, 3-H), 5.51
(1H, s, 3-H), 5.85 (1H, s, 1-H), 6.34 (1H, dd, J 2.5 and 8.5,
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2 B. C. B. Bezuidenhoudt, E. V. Brandt, D. G. Roux and P. H. van
5Ј-H), 6.44 (1H, d, J 2.6, 3Ј-H), 6.86 (1H, d, J 8.4, 6Ј-H) and
7.20–7.41 (5H, m, Ar-H); δC(CDCl3) 55.8 (OMe), 75.8 (C-1),
103.0 (C-3), 106.4 (C-3Ј), 115.6 (C-5Ј), 118.3 (C-1Ј), 127.6 (C-2Љ
and -6Љ), 128.5 (C-4Љ), 129.0 (C-3Љ and -5Љ), 129.8 (C-6Ј), 139.5
(C-1Љ), 149.5 (C-2), 157.5 (C-2Ј) and 161.1 (C-4Ј); m/z 254 (Mϩ,
5%), 239 (18), 238 (Mϩ Ϫ 18, 100), 237 (68), 223 (13), 194 (7),
165 (12), 161 (22), 117 (11) and 58 (34) (Found: Mϩ, 256.1084.
C16H16O3 requires M, 256.1099).
Rooyen, J. Chem. Soc., Perkin Trans. 1, 1980, 2179.
3 R. G. Cooke and I. D. Rae, Aust. J. Chem., 1964, 17, 379.
4 F. E. King, T. J. King and A. J. Warwick, J. Chem. Soc., 1952, 1920.
5 B. C. B. Bezuidenhoudt, E. V. Brandt and D. G. Roux, J. Chem. Soc.,
Perkin Trans. 1, 1981, 263.
6 H. Adlerceutz, Front. Gastrointest. Res., 1988, 14, 165.
7 D. A. Shutt and R. I. Cox, J. Endocrinol., 1972, 52, 299.
8 T. J. Batterham, D. A. Shutt, N. K. Hart, A. W. H. Braden and
H. J. Tweeddale, Aust. J. Agric. Res., 1971, 22, 131.
9 A. W. H. Braden, R. I. Thain and D. A. Shutt, Aust. J. Agric. Res.,
1971, 22, 663.
1-(2-Hydroxyphenyl)-2-phenylprop-2-en-1-ol 3c
10 H. Adlercreutz, P. I. Musey, T. Fotsis, C. Bannwart, K. Wähälä,
T. Mäkelä, G. Brunow and T. Hase, Clin. Chim. Acta, 1986, 158,
147.
11 C. Bannwart, H. Adlercreutz, T. Fotsis, K. Wähälä, T. Hase and
G. Brunow, Finn. Chem. Lett., 1984, 11, 120.
12 H. Adlercreutz, T. Fotsis, C. Bannwart, K. Wähälä, T. Mäkelä,
G. Brunow and T. Hase, J. Steroid Biochem., 1986, 25, 791.
13 H. Adlercreutz, T. Fotsis, C. Bannwart, K. Wähälä, G. Brunow and
T. Hase, Clin. Chim. Acta, 1991, 199, 263.
14 H. Adlercreutz, H. Markkanen and S. Watanabe, Lancet, 1993,
342, 1209.
15 L. Coward, M. Kirk, N. Albin and S. Barnes, Clin. Chim. Acta,
1996, 247, 121.
16 H. Adlercreutz, T. Fotsis, M. S. Kurzer, K. Wähälä, T. Mäkelä and
T. Hase, Anal. Biochem., 1995, 225, 101.
17 M. S. Kurzer, J. W. Lampe, M. C. Martini and H. Adlercreutz,
Cancer Epidemiol. Biomarkers Prev., 1995, 4, 353.
Flash chromatography eluent: n-hexane–acetone (7:4). Amor-
phous solid. λmax(EtOH)/nm 205 (ε/dm3 molϪ1 cmϪ1 24 500),
240 (8680) and 278 (2680); νmax/cmϪ1 3497 (OH) and 3179
(OH); δH(CDCl3) 5.27 (1H, s, 3-H), 5.51 (1H, s, 3-H), 5.91 (1H,
s, 1-H), 6.79 (1H, dt, J 1.3 and 7.5, 5Ј-H), 6.89 (1H, dd, J 1.2
and 8.2, 3Ј-H), 6.98 (1H, dd, J 1.7 and 7.6, 6Ј-H), 7.18 (dt, 1H,
J 1.7 and 7.7, 4Ј-H), 7.28–7.41 (5H, m, Ar-H) and 7.7 (1H, br s,
OH); δC(CDCl3) 76.3 (C-1), 115.5 (C-3), 117.2 (C-3Ј), 119.9
(C-5Ј), 124.7 (C-1Ј), 127.6 (C-2Љ and -6Љ), 128.1 (C-4Љ), 128.5
(C-6Ј), 128.6 (C-3Љ and -5Љ), 129.4 (C-4Ј), 138.7 (C-1Љ), 148.6
(C-2) and 155.8 (C-2Ј); m/z 226 (Mϩ, 3%), 222 (8), 209 (16), 208
(Mϩ Ϫ 18, 100), 207 (93), 194 (10), 178 (26), 165 (10), 131 (30)
and 104 (15) (Found: Mϩ, 226.0996. C15H14O2 requires M,
226.0993).
18 H. Adlercreutz, T. Fotsis, C. Bannwart, T. Mäkelä, K. Wähälä,
G. Brunow and T. Hase, Advances in Mass Spectroscopy – 85,
Proceedings of the 10th International Mass Spectroscopy Conference,
ed. J. F. L. Todd, John Wiley, Chichester, 1986, p. 2179.
19 K. R. Price and G. R. Fenwick, Food Add. Contam., 1985, 2, 73.
20 G. E. Kelly, C. Nelson, M. A. Waring, G. E. Joannou and A. Y.
Reeder, Clin. Chim. Acta, 1993, 223, 9.
21 G. E. Joannou, G. E. Kelly, A. Y. Reeder, M. Waring and C. Nelson,
J. Steroid Biochem. Mol. Biol., 1995, 54, 167.
22 S. Heinonen, K. Wähälä and H. Adlercreutz, Anal. Biochem., 1999,
in press.
1-(2-Hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)prop-2-en-
1-ol 3d
Flash chromatography eluent: n-hexane–acetone (1:1) Amor-
phous solid. λmax(EtOH)/nm 206 (ε/dm3molϪ1 cmϪ1 41 700), 237
(12 600) and 260 (15 400); νmax/cmϪ1 3354 (OH); δH([2H6]-
acetone) 3.68 (3H, s, OCH3), 5.35 (1H, s, 3-H), 5.39 (1H, s, 3-
H), 5.99 (1H, s, 1-H), 6.30 (1H, dd, J 2.4 and 8.4, 5Ј-H), 6.36
(1H, d, J 2.6, 3Ј-H), 6.73 (2H, d, J 8.6, 3Љ-H and 5Љ-H), 7.01
(1H, d, J 8.4, 6Ј-H), 7.30 (2H, d, J 8.8, 2Љ-H and 6Љ-H); δC([2H6]-
acetone) 55.4 (OCH3), 72.1 (C-1), 102.4 (C-3), 105.7 (C-3Ј),
111.5 (C-5Ј), 115.8 (C-3Љ and -5Љ), 121.4 (C-1Ј), 128.9 (C-2Љ and
-6Љ), 129.9 (C-6Ј), 132.2 (C-1Љ), 151.1 (C-2), 157.6 (C-2Ј), 157.9
(C-4Ј) and 161.1 (C-4Љ); m/z 272 (Mϩ, 8%), 268 (6), 255 (18), 254
(100), 253 (65), 239 (26), 161 (9), 153 (21), 127 (12) and 121 (16)
(Found: Mϩ, 272.1047. C16H16O4 requires M, 272.1048).
23 V. N. Gupta and T. R. Seshadri, Proc. Indian Acad. Sci., Sect. A,
1956, 44, 223.
24 A. C. Jain and P. Paliwar, Indian J. Chem., Sect. B, 1988, 27, 985.
25 K. Wähälä, PhD Thesis, University of Helsinki, 1992.
26 J. W. Clark-Lewis and R.W. Jemison, Aust. J. Chem., 1965, 18, 1791.
27 C. D. Foxall and J. W. W. Morgan, J. Chem. Soc., 1963, 5573.
28 V. Szabó and E. Antal, Acta Chim. Acad. Sci. Hung., 1976, 90, 381.
29 Á. Major, Z. Nagy and M. Nógrádi, Acta Chim. Acad. Sci. Hung.,
1980, 104, 85.
30 M. Süsse, S. Johne and M. Hesse, Helv. Chim. Acta, 1992, 75, 457.
31 K. Wähälä and T. Hase, J. Chem. Soc., Perkin Trans. 1, 1991, 3005.
32 K. Wähälä, T. Hase and H. Adlercreutz, Proc. Soc. Exp. Biol. Med.,
1995, 208, 27.
33 K. Wähälä, A. Salakka and H. Adlercreutz, Proc. Soc. Exp. Biol.
Med., 1998, 217, 293.
Acknowledgements
Funding to A. S. from the Foundation of Emil Aaltonen and to
K. W. from the University of Helsinki is gratefully acknow-
ledged. We thank Dr Jorma Matikainen for running the mass
spectra.
34 R. A. Micheli, A. N. Booth, A. L. Livingston and E. M. Bickoff,
J. Med. Pharm. Chem., 1962, 5, 321.
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