Total synthesis of chiricanine A, arahypin-1, trans -arachidin-2, trans -arachidin-3, and arahypin-5 from peanut seeds

Article abstract of DOI:10.1021/np100696f

The first and efficient syntheses of the naturally occurring prenylated stilbenes chiricanine A (2), arahypin-1 (3), trans-arachidin-2 (4), trans-arachidin-3 (5), and arahypin-5 (6) are described. Syntheses of 2 and 3 were accomplished by either a converg

Full text of DOI:10.1021/np100696f

ARTICLE
pubs.acs.org/jnp
Total Synthesis of Chiricanine A, Arahypin-1, trans-Arachidin-2,
trans-Arachidin-3, and Arahypin-5 from Peanut Seeds
Byung Ho Park, Hee Jin Lee, and Yong Rok Lee*
School of Chemical Engineering and Technology, Yeungnam University, Gyeongsan 712-749, Korea
S Supporting Information
b
ABSTRACT: The first and efficient syntheses of the naturally
occurring prenylated stilbenes chiricanine A (2), arahypin-1
(3), trans-arachidin-2 (4), trans-arachidin-3 (5), and arahypin-5
(6) are described. Syntheses of 2 and 3 were accomplished by
either a convergent sequence or a one-step reaction starting
from pinosylvin. Syntheses of 4, 5, and 6 were achieved from
(E)-3,5-bis-methoxymethyl-40-triisopropylsilyloxystilbene ob-
tained by a Horner-Wadsworth-Emmons reaction between
a benzaldehyde possessing bis-methoxymethyl ether groups
and a benzyl phosphonate with a triisopropylsilyloxy group.
he peanut (Arachis hypogaea), which is a species in the
legume family (Leguminosae), has been cultivated around
’ RESULTS AND DISCUSSION
T
Recently we developed new methodology for the formation of
pinosylvin (10), bearing a stilbene skeleton, starting from 3,5-
dimethoxybenzaldehyde (7) and benzyl phosphonate (8)
through a Horner-Wadsworth-Emmons reaction followed
by demethylation as shown in Scheme 1.24 As an application of
this methodology, we describe herein an efficient synthesis of
chiricanine A (2), arahypin-1 (3), trans-arachidin-2 (4), trans-
arachidin-3 (5), and arahypin-5 (6), each with a prenyl group on
the stilbene skeleton.
An initial attempt toward the syntheses of chiricanine A (2)
and arahypin-1 (3) was made using pinosylvin (10) as the
starting material (Scheme 2). Reaction of 10 with 2.2 equiv of
methoxymethyl chloride in the presence of NaH afforded 11 in
82% yield. Treatment of 11 with n-butyllithium followed by
addition of prenyl bromide to trap the intermediate anion
afforded the expected compound 12 (61%), which was depro-
tected with concentrated HCl in methanol to give 2 in 67% yield.
The spectroscopic data of synthetic 2 were identical to those of
the natural product reported in the literature.9 In addition, when
11 was treated with n-BuLi in THF, followed by addition of
isovaleraldehyde, 13 was obtained in 71% yield. Elimination of
the OH group in 13 with POCl3 in pyridine afforded 14 in 61%
yield. To complete the synthesis of 3, deprotection of 14 with
concentrated HCl in methanol gave desired product 3 in low
yield (25%) due to instability of the compound. The trans-
configuration was confirmed by observation of the expected
chemical shifts and coupling constants of two olefinic H-atoms at
δ 6.31 (d, J = 16.5 Hz) and 6.15 (dd, J = 16.5, 6.6 Hz). When
other Brønsted acids such as p-TsOH, TFA, and CSA were used,
the world and has become an economically and nutritionally
important crop.1 Approximately 50 different genera of fungi are
parasitic on the peanut,2 of which Aspergillus flavus and Aspergillus
parasiticus are very dangerous and important because of their
ability to produce carcinogenic aflatoxins.3 However, the peanut
plant can resist fungal attacks by promptly producing stilbene-
derived phytoalexins.4 A study of a natural phytoalexin-based
peanut resistance has attracted the attention of researchers
because the knowledge and understanding of this mechanism
of resistance can be crucial for breeding new fungi-resistant
peanut cultivars.5 Recently, several types of stilbene derivatives
(1-6) as fungi-resistant materials were isolated from peanut
seeds challenged by an Aspergillus caelatus strain6 and have been
shown to play a defensive role against invasive fungi.7 Resveratrol
(1) is known to exert a variety of promising biological activities
and is beneficial to human health.8 Chiricanine A (2) was also
isolated from Lonchocarpus chiricanus9 and has shown antifungal
activity against Cladosporium cucumerinum.9 Importantly, poly-
phenols bearing the stilbene moiety occur widely in nature10 and
have a variety of interesting biological properties, including anti-
microbial,11 antimalarial,12 antioxidant,13 antileukemic,14 anti-
platelet aggregative,15 anticarcinogenic,16 anti-HIV,17 protein
tyrosine kinase inhibitory,18 anti-inflammatory,19 antimutagenic,20
antifungal,21 and hepatoprotective22 activities. In particular, the
presence of a prenyl group on the aromatic ring of stilbenoids can
lead to a remarkable increase in corresponding bioactivities.23
This range of important biological activities and properties has
stimulated research into the synthesis of naturally occurring
stilbenoids. The structures of natural products 2-6 have been
established by spectroscopic analyses, but no total syntheses of
chiricanine A (2), arahypin-1 (3), trans-arachidin-2 (4), trans-
arachidin-3 (5), and arahypin-5 (6) have been reported.
Received: September 28, 2010
Published: February 24, 2011
r
Copyright
2011 American Chemical Society and
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Chart 1
Scheme 1
Scheme 2
the yield did not increase. Thus, another new approach to the
synthesis of 3 was attempted from pinosylvin (10), as a one-step
reaction. Interestingly, treatment of 10 with isovaleraldehyde in
the presence of 20 mol % ethylenediamine diacetate in refluxing
benzene for 24 h gave 3 in 54% yield. The spectral data of
synthetic 3 were in agreement with those previously reported.6
Next, the synthesis of naturally occurring trans-arachidin-2 (4)
was attempted (Scheme 3). The Horner-Wadsworth-Emmons
reaction between benzaldehyde (15), having MOM ether
groups, and benzyl phosphonate (16), with a triisopropylsilyloxy
group, in the presence of potassium tert-butoxide in THF gave
desired compound 17 in 82% yield. Deprotonation at the
2-position of the bis-MOM ether of 17 with n-BuLi in THF
followed by addition of prenyl bromide provided 18 in 80% yield.
Deprotection of 18 with concentrated HCl in methanol provided
19 in 80% yield, which was treated with TBAF to give 4 in
75% yield.
Finally, the syntheses of naturally occurring trans-arachidin-3
(5) and arahypin-5 (6) were carried out starting from 17 as
outlined in Scheme 4. Deprotection of the two MOM ether
groups with concentrated HCl solution in methanol gave 20 in
80% yield. Treatment of 20 with isovaleraldehyde in the presence
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ARTICLE
Scheme 3
Scheme 4
of 20 mol % ethylenediamine diacetate afforded 21 in 52% yield.
Cleavage of the TIPS group with TBAF gave 5 in 74% yield. To
complete the synthesis of arahypin-5 (6), a benzopyran forma-
tion reaction was next attempted. Reaction of 20 with 3-methyl-
2-butenal in the presence of 20 mol % EDDA in refluxing xylene
for 5 h gave cycloadduct 22 in 55% yield. Deprotection of 22 with
TBAF in THF gave 6 in 95% yield.
In conclusion, total synthesis of naturally occurring and
biologically interesting chiricanine A (2), arahypin-1 (3), trans-
arachidin-2 (4), trans-arachidin-3 (5), and arahypin-5 (6) is
described. The synthesis of 2 and 3 was accomplished by either
a convergent sequence or a one-step reaction starting from
pinosylvin (10). The syntheses of 4, 5, and 6 were achieved
from stilbene 17 obtained by a Horner-Wadsworth-Emmons
reaction of benzaldehyde 15, having MOM ether groups, with
benzyl phosphonate 16, with a triisopropylsilyloxy group, in a
straightforward fashion.
Jasco FTIR 5300 spectrophotometer. HRMS were carried out at the
Korea Basic Science Institute. Abbreviations: MOM = methoxymethyl,
TIPS = triisopropylsilyl, TBAF = tetrabutylammonium fluoride, EDDA =
ethylenediamine diacetate.
(E)-3,5-Bis-methoxymethoxystilbene (11). Methoxymethyl
chloride (0.51 g, 6.3 mmol) was added to a solution of 10 (0.509 g,
2.4 mmol) and NaH (0.288 g, 12.0 mmol) in DMF (20 mL) at 0 °C. The
reaction mixture was stirred at room temperature for 12 h, and then H2O
(40 mL) was added at 0 °C. The reaction mixture was extracted with
EtOAc (3 ꢀ 30 mL), and the extract was washed with saturated NH4Cl
solution (30 mL) and H2O (30 mL), dried (MgSO4), and evaporated
under reduced pressure. Flash chromatography on silica gel using
1
hexane/ethyl acetate (20:1) afforded 11 (0.591 g, 82%) as an oil.: H
NMR (300 MHz, CDCl3) δ 7.41 (2H, d, J = 7.2 Hz), 7.26 (2H, dd, J =
7.5, 7.2 Hz), 7.17 (1H, t, J = 7.5 Hz), 7.01 (1H, d, J = 16.0 Hz), 6.93 (1H,
d, J = 16.0 Hz), 6.79 (2H, s), 6.57 (1H, s), 5.01 (4H, s), 3.41 (6H, s); 13C
NMR (75 MHz, CDCl3) δ 158.5, 158.5, 139.5, 137.0, 129.3, 128.6,
128.6, 128.3, 127.7, 126.5, 126.5, 107.8, 107.8, 104.2, 94.4, 94.4, 56.0,
56.0; IR (neat) 2953 (C-H), 2825 (C-H), 1591, 1454, 1400, 1282,
1213, 1147, 1084, 1035, 962, 923, 841, 752 cm-1; HREIMS, 70 eV, m/z
300.1364 (calcd for C18H20O4 300.1362).
’ EXPERIMENTAL SECTION
General Experimental Procedures. Merck precoated silica gel
plates (Art. 5554) with a fluorescent indicator were used for analytical
TLC. Flash column chromatography (CC) was performed using silica
gel 9385 (Merck). All experiments were carried out in a nitrogen
atmosphere. 1H and 13C NMR spectra were recorded on a Bruker
model ARX (300 and 75 MHz, respectively) spectrometer in CDCl3,
CD3OD, or acetone-d6 as the solvent. IR spectra were recorded on a
(E)-3,5-Bis-methoxymethoxy-2-(3-methylbut-2-enyl)stil-
bene (12). n-BuLi (0.72 mL, 2.5 M in hexane, 1.8 mmol) was added at
0 °C to a solution of 11 (0.451 g, 1.5 mmol) in THF (20 mL), and the
resulting solution was stirred at 0 °C for 2 h. Prenyl bromide (0.238 g, 1.6
mmol) was added dropwise to the reaction mixture at 0 °C, which was
stirred at room temperature for 10 h. The reaction mixture was
quenched with saturated NH4Cl solution (20 mL) and extracted with
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EtOAc (3 ꢀ 30 mL). The combined extracts were washed with water
(30 mL), dried (MgSO4), and evaporated under reduced pressure. Flash
chromatography on silica gel using hexane/EtOAc (20:1) afforded 12
(0.337 g, 61%) as an oil: 1H NMR (300 MHz, CDCl3) δ 7.49 (2H, d, J =
7.2 Hz), 7.34 (2H, dd, J = 7.5, 7.2 Hz), 7.23 (1H, t, J = 7.5 Hz), 7.03 (2H,
s), 6.94 (2H, s), 5.24 (4H, s), 5.21(1H, t, J = 7.2 Hz), 3.50 (6H, s), 3.39
(2H, d, J = 7.2 Hz), 1.79 (3H, s), 1.67 (3H, s); 13C NMR (75 MHz,
CDCl3) δ 155.8, 155.8, 137.3, 136.3, 131.1, 128.8, 128.6, 128.6, 128.3,
127.5, 126.5, 126.5, 122.7, 119.9, 106.2, 106.2, 94.5, 94.5, 56.0, 56.0, 25.8,
22.8, 17.5; IR (neat) 2912 (C-H), 1600, 1576, 1438, 1394, 1316, 1211,
1153, 1102, 1048, 944, 750 cm-1; HREIMS, 70 eV, m/z 368.1990 (calcd
for C23H28O4 368.1988).
56.2, 33.1, 22.7, 22.7; IR (neat) 2955 (C-H), 1600, 1447, 1393, 1152,
1044, 965, 824, 739 cm-1; HREIMS, 70 eV, m/z 368.1985 (calcd for
C23H28O4 368.1988).
Arahypin-1 (3) from Compound 14. To a solution of 14 (0.184 g,
0.5 mmol) in MeOH (5 mL) was added concentrated HCl (0.5 mL),
and the reaction mixture was stirred at room temperature for 10 h. The
reaction was diluted with saturated NaHCO3 solution (30 mL) and
extracted with EtOAc (3 ꢀ 30 mL). Removal of solvent at reduced
pressure left an oily residue, which was then purified by CC on silica
gel with hexane/EtOAc (4:1) to give 3 (0.035 g, 25%) as an oil: IR
(neat) 3409 (OH), 2949 (C-H), 1624, 1574, 1433, 1360, 1301, 1028,
1
975, 828 cm-1; H NMR (300 MHz, CDCl3) δ 7.46 (2H, d, J =
Chiricanine A (2). To a solution of 12 (0.184 g, 0.5 mmol) in
MeOH (5 mL) was added concentrated HCl (0.2 mL), and the reaction
mixture was stirred at room temperature for 10 h. The reaction mixture
was diluted with saturated NaHCO3 solution (30 mL) and extracted
with EtOAc (3 ꢀ 30 mL). Removal of solvent at reduced pressure left an
oily residue, which was then purified by CC on silica gel with hexane/
7.6 Hz), 7.33 (2H, t, J = 7.6 Hz), 7.24 (1H, t, J = 7.6 Hz), 7.03 (1H, d,
J = 16.2 Hz), 6.93 (1H, d, J = 16.2 Hz), 6.63 (2H, s), 6.31 (1H, d, J =
16.5 Hz), 6.15 (1H, dd, J = 16.5, 6.6 Hz), 5.34 (1H, br s), 2.60-2.49
(1H, m), 1.13 (6H, d, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ
153.8, 153.8, 145.7, 137.6, 137.0, 129.1, 128.6, 128.6, 127.9, 127.6,
126.5, 126.5, 117.3, 111.8, 105.8, 105.8, 32.2, 22.3, 22.3; HREIMS, 70
eV, m/z 280.1466 (calcd for C19H20O2 280.1463).
1
EtOAc (4:1) to give 2 (0.094 g, 67%) as an oil: H NMR (300 MHz,
CDCl3) δ 7.46 (2H, d, J = 7.2 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.24 (1H, t, J
= 7.2 Hz), 6.99 (1H, d, J = 16.5 Hz), 6.91 (1H, d, J = 16.5 Hz), 6.57 (2H,
s), 5.27 (1H, t, J = 6.9 Hz), 3.42 (2H, d, J = 6.9 Hz), 1.82 (3H, s), 1.76
(3H, s); 13C NMR (75 MHz, CDCl3) δ 155.0, 155.0, 137.2, 136.8,
135.6, 128.7, 128.7, 128.6, 128.0, 127.6, 126.5, 126.5, 121.3, 113,2, 106.5,
106.5, 25.8, 22.5, 17.9; IR (neat) 3412 (O-H), 2973 (C-H), 2925
Arahypin-1 (3) from Compound10. Toasolutionof10(0.212g,
1.0 mmol) and isovaleraldehyde (0.129 g, 1.5 mmol) in benzene (20 mL)
was added ethylenediamine diacetate (36 mg, 0.2 mmol) at room
temperature. The reaction mixture was refluxed for 10 h and then cooled
to room temperature. Evaporation of solvent and purification by CC on
silica gel using hexane/EtOAc (4:1) gave 3 (0.151 g, 54%) as an oil. The
spectral data were the same as described above.
(C-H), 1611, 1584, 1445, 1352, 1264, 1158, 1051, 963, 826, 743 cm-1
HREIMS, 70 eV, m/z 280.1466 (calcd for C19H20O2: 280.1463).
;
(E)-3,5-Bis-methoxymethoxy-40-triisopropylsilyloxystil-
bene (17). To a solution of aldehyde 15 (0.679 g, 3.0 mmol) and
benzyl phosphonate 16 (1.202 g, 3.0 mmol) in THF (30 mL) was added
t-BuOK (0.717 g, 6.4 mmol) at 0 °C. The reaction mixture was stirred at
0 °C for 5 h. The reaction was quenched by addition of H2O (30 mL)
and extracted with EtOAc (3 ꢀ 30 mL). The combined organic layer was
washed with NH4Cl solution (30 mL), H2O (30 mL), and brine
(30 mL), dried over MgSO4, and concentrated at reduced pressure.
The removal of the solvent under reduced pressure left an oily residue,
which was then purified by CC on silica gel using hexane/EtOAc (4:1)
to give 17 (1.163 g, 82%) as an oil: 1H NMR (300 MHz, CDCl3) δ 7.35
(2H, d, J = 9.0 Hz), 7.01 (1H, d, J = 16.2 Hz), 6.88-6.81 (5H, m), 6.60
(1H, t, J = 2.0 Hz), 5.17 (4H, s), 3.48 (6H, s), 1.41-1.20 (3H, m), 1.09
(18H, d, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 158.2, 158.2, 155.7,
139.7, 129.8, 128.8, 127.5, 127.5, 126.0, 119.8, 119.8, 107.4, 107.4, 103.6,
94.2, 94.2, 55.7, 55.7, 17.6 (6 carbons), 12.4 (3 carbons); IR (neat) 2952
(C-H), 2868 (C-H), 1597, 1509, 1463, 1396, 1275, 1151, 1037, 918,
841 cm-1; HREIMS, 70 eV, m/z 472.2646 (calcd for C27H40O5Si
472.2645).
(E)-3,5-Bis-methoxymethoxy-2-(1-hydroxy-3-methylbutyl)-
stilbene (13). n-BuLi (0.8 mL, 2.5 M in hexane, 2.0 mmol) was added
at 0 °C to a solution of 11 (0.541 g, 1.8 mmol) in THF (20 mL), and the
resulting solution was stirred at 0 °C for 2 h. Isovaleraldehyde (0.164 g,
1.9 mmol) was added dropwise to the reaction mixture at 0 °C, which
was stirred at room temperature for 10 h. The reaction mixture was
quenched with saturated NH4Cl solution (20 mL) and extracted with
EtOAc (3 ꢀ 30 mL). The extract was washed with H2O (30 mL), dried
(MgSO4), and evaporated under reduced pressure. Flash chromatogra-
phy on silica gel using hexane/EtOAc (4:1) afforded 13 (0.494 g, 71%)
as an oil: 1H NMR (300 MHz, CDCl3) δ 7.49 (2H, d, J = 7.2 Hz), 7.34
(2H, t, J = 7.2 Hz), 7.24 (1H, t, J = 7.2 Hz), 7.01 (1H, d, J = 16.2 Hz), 7.07
(1H, d, J = 16.2 Hz), 6.97 (2H, s), 5.28-5.25 (1H, m), 5.26 (4H, s), 3.50
(6H, s), 1.93-1.84 (1H, m), 1.80-1.71 (1H, m), 1.67-1.58 (1H, m),
0.99 (3H, d, J = 6.6 Hz), 0.95 (3H, d, J = 6.6 Hz); 13C NMR (75 MHz,
CDCl3) δ 155.5, 155.5, 137.7, 137.0, 129.0, 128.6, 128.6, 128.2, 127.6,
126.5, 126.5, 121.3, 106.3, 106.3, 94.5, 94.5, 66.3, 56.2, 56.2, 47.0, 25.0,
23.2, 22.4; IR (neat) 3600 (O-H), 2953 (C-H), 1603 (C-H), 1576,
1448, 1215, 1152, 1100, 1042, 921, 751 cm-1; HREIMS, 70 eV, m/z
386.2097 (calcd for C23H30O5 386.2093).
(E)-3,5-Bis-methoxymethoxy-2-{(E)-3-methylbut-1-enyl)}-
stilbene (14). Compound 13 (0.425 g, 1.1 mmol) was dissolved in
pyridine (10 mL), and the reaction mixture was cooled to 0 °C. POCl3
(0.506 g, 3.3 mmol) was added dropwise. The reaction was stirred at
room temperature for 1 h, then heated at 100 °C for 1 h. After cooling to
room temperature, the reaction mixture was diluted with EtOAc
(50 mL) and poured into 2 N HCl (50 mL), and the phases were
separated. The aqueous phase was extracted with EtOAc (3 ꢀ 30 mL).
The extract was washed with 2 N HCl (50 mL) and brine (50 mL), dried
(MgSO4), and concentrated under reduced pressure. Flash chromatog-
raphy on silica gel using hexane/EtOAc (4:1) afforded 14 (0.259 g, 64%)
as an oil: 1H NMR (300 MHz, CDCl3) δ 7.50 (2H, d, J = 7.2 Hz), 7.34
(2H, t, J = 7.2 Hz), 7.25 (1H, t, J = 7.2 Hz), 7.01 (1H, d, J = 16.2 Hz), 7.07
(1H, d, J = 16.0 Hz), 6.95 (2H, s), 6.60-6.58 (2H, m), 5.24 (4H, s), 3.52
(6H, s), 2.53-2.43 (1H, m), 1.10 (6H, d, J = 6.6 Hz); 13C NMR (75
MHz, CDCl3) δ 155.9, 155.9, 143.1, 137.2, 136.5, 128.7, 128.6, 128.6,
128.5, 128.5, 127.6, 126.5, 126.5, 117.2, 107.2, 107.2, 94.9, 94.9, 56.2,
(E)-3,5-Bis-methoxymethoxy-2-(3-methylbut-2-enyl)-40-
triisopropylsilyloxystilbene (18). n-BuLi (0.44 mL, 2.5 M in
hexane, 1.1 mmol) was added at 0 °C to a solution of 17 (0.473 g,
1.0 mmol) in THF (20 mL), and the resulting solution was stirred at
0 °C for 2 h. Prenyl bromide (0.164 g, 1.1 mmol) was added dropwise to
the reaction mixture at 0 °C, which was stirred at room temperature for
10 h. The reaction was quenched with saturated NH4Cl solution
(20 mL) and extracted with EtOAc (3 ꢀ 30 mL). The combined
extracts were washed with H2O (30 mL), dried (MgSO4), and evapo-
rated under reduced pressure. Flash chromatography on silica gel using
1
hexane/EtOAc (5:1) afforded 18 (0.433 g, 80%) as an oil: H NMR
(300 MHz, CDCl3) δ 7.36 (2H, d, J = 7.8 Hz), 7.01-6.84 (6H, m), 5.23
(4H, s), 5.22 (1H, t, J = 6.5 Hz), 3.50 (6H, s), 3.39 (2H, d, J = 6.5 Hz),
1.78 (3H, s), 1.67 (3H, s), 1.38-1.19 (3H, m), 1.11 (18H, d, J = 6.6 Hz);
13C NMR (75 MHz, CDCl3) δ 155.8, 155.8, 155.7, 136.8, 131.0, 130.4,
128.0, 127.6, 127.6, 126.7, 122.8, 120.1, 120.1, 119.5, 106.0, 106.0, 94.5,
94.5, 56.0, 56.0, 25.8, 22.8, 17.9 (6 carbons), 17.8, 12.7 (3 carbons);
IR (neat) 2947 (C-H), 1599, 1511, 1452, 1271, 1156, 1053, 916 cm-1
HREIMS, 70 eV, m/z 540.3268 (calcd for C32H48O5Si 540.3271).
;
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(E)-3,5-Dihydroxy-2-(3-methylbut-2-enyl)-40-triisopropyl-
silyloxystilbene (19). To a solution of 18 (0.27 g, 0.5 mmol) in
MeOH (5 mL) was added concentrated HCl (0.5 mL), and the reaction
mixture was stirred at room temperature for 10 h. The mixture was
diluted with saturated NaHCO3 solution (30 mL) and extracted with
EtOAc (3 ꢀ 30 mL). Removal of solvent at reduced pressure left an oily
residue, which was then purified by CC on silica gel with hexane/EtOAc
(4:1) to give 19 (0.181 g, 80%) as an oil: IR (neat) 2946 (C-H), 2865
2871 (C-H), 1601, 1510, 1447, 1268, 1168, 1036, 909 cm-1; HREIMS,
70 eV, m/z 452.2743 (calcd for C28H40O3Si 452.2747).
trans-Arachidin-3 (5). To the solution of 21 (0.045 g, 0.1 mmol)
in THF (10 mL) was added TBAF (0.2 mL, 0.2 mmol, 1.0 M in THF) at
0 °C, and the reaction mixture was stirred at room temperature for 3 h.
The reaction mixture was quenched by the addition of saturated NH4Cl
solution (30 mL) and extracted with EtOAc (3 ꢀ 30 mL). The organic
layer was washed with water (30 mL), dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The residue was purified by
CC with hexane/EtOAc (4:1) and afforded 5 (0.022 g, 74%) as an oil: IR
(neat) 3393 (O-H), 2931 (C-H), 1598, 1512, 1435, 1246, 1034,
(C-H), 1598, 1509, 1456, 1391, 1269, 1155, 1103, 1051, 916, 838 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.33 (2H, d, J = 8.7 Hz), 7.01 (1H, d, J =
16.2 Hz), 6.85 (2H, d, J = 8.7 Hz), 6.76 (1H, d, J = 16.8 Hz), 6.53 (2H, s),
5.40 (1H, br s), 5.27 (1H, t, J = 6.6 Hz), 3.41 (2H, d, J = 6.6 Hz), 1.82
(3H, s), 1.75 (3H, s), 1.34-1.20 (3H, m), 1.11 (18H, d, J = 6.9 Hz); 13C
NMR (75 MHz, CDCl3) δ 155.8, 155.0, 155.0, 137.2, 135.3, 130.2,
128.3, 127.6, 127.6, 125.9, 121.5, 120.1, 120.1, 112.8, 106.2, 106.2, 25.7,
22.5, 17.8 (7 carbons), 12.6 (3 carbons); HREIMS, 70 eV, m/z 452.2745
(calcd for C28H40O3Si 452.2747).
1
821 cm-1; H NMR (300 MHz, CDCl3) δ 7.36 (2H, d, J = 8.7 Hz),
6.97 (1H, d, J = 16.2 Hz), 6.80 (2H, d, J = 8.7 Hz), 6.77 (1H, d, J =
16.2 Hz), 6.60 (2H, s), 6.29 (1H, d, J = 16.5 Hz), 6.12 (1H, dd, J = 16.5,
6.6 Hz), 5.09 (1H, s), 2.60-2.49 (1H, m), 1.13 (6H, d, J = 6.6 Hz); 13C
NMR (75 MHz, acetone-d6) δ 158.2, 157.1, 157.1, 141.3, 137.7, 130.0,
128.7, 128.7, 128.6, 126.6, 119.3, 116.5, 116.5, 112.7, 106.1, 106.1, 34.0,
23.3, 23.3; HREIMS, 70 eV, m/z 296.1409 (calcd for C19H20O3 296.1412).
(E)-2,2-Dimethyl-7-[2-(4-triisopropylsilanyloxyphenyl)-
vinyl]-2H-chromen-5-ol (22). To a solution of 20 (0.115 g,
0.3 mmol) and 3-methyl-2-butenal (0.034 g, 0.4 mmol) in benzene
(20 mL) was added ethylenediamine diacetate (11 mg, 0.06 mmol) at
room temperature. The reaction mixture was refluxed for 10 h and
then cooled to room temperature. Evaporation of solvent and CC on
silica gel using hexane/EtOAc (5:1) gave 22 (0.074 g, 55%) as an oil:
IR (neat) 3396 (O-H), 3028 (dC-H), 2943 (C-H), 2865 (C-H),
1600, 1565, 1509, 1462, 1271, 1168, 1139, 1115, 1060, 912, 884 cm-
1; 1H NMR (300 MHz, CDCl3) δ 7.32 (2H, d, J = 8.4 Hz), 6.95 (1H,
d, J = 16.2 Hz), 6.83 (2H, d, J = 8.4 Hz), 6.74 (1H, d, J = 16.2 Hz), 6.63
(1H, d, J = 9.9 Hz), 6.57 (1H, s), 6.46 (1H, s), 5.56 (1H, d, J = 9.9 Hz),
1.34 (6H, s), 1.26-1.11 (3H, m), 1.01 (18H, d, J = 6.9 Hz); 13C NMR
(75 MHz, CDCl3) δ 155.9, 154.0, 151.6, 138.8, 130.2, 128.9, 128.6,
127.7, 127.7, 126.1, 120.1, 120.1, 116.6, 109.0, 106.9, 106.1, 76.0,
27.8, 27.8, 17.9 (6 carbons), 12.7 (3 carbons); HREIMS, 70 eV, m/z
450.2593 (calcd for C28H38O3Si 450.2590).
trans-Arachidin-2 (4). To the solution of 19 (0.136 g, 0.3 mmol)
in THF (10 mL) was added TBAF (0.6 mL, 0.6 mmol, 1.0 M in THF) at
0 °C, and the reaction mixture was stirred at room temperature for 3 h.
The reaction mixture was quenched by addition of saturated NH4Cl
solution (30 mL) and extracted with EtOAc (3 ꢀ 30 mL). The organic
layer was washed with water (30 mL), dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The resulting residue was
purified by CC with hexane/EtOAc (4:1) to afford 4 (0.067 g, 75%) as
an oil: 1H NMR (300 MHz, acetone-d6) δ 8.41 (1H, s), 8.07 (1H, s),
7.38 (2H, d, J = 8.7 Hz), 6.93 (1H, d, J = 16.2 Hz), 6.84-6.79 (3H, m),
6.59 (2H, s), 5.30 (1H, t, J = 7.2 Hz), 3.35 (2H, d, J = 7.2 Hz), 1.76 (3H,
s), 1.64 (3H, s); 13C NMR (75 MHz, acetone-d6) δ 158.0, 157.0, 157.0,
137.3, 130.8, 130.1, 128.6, 128.6, 128.2, 127.0, 124.4, 116.5, 116.5, 115.3,
105.8, 105.8, 26.0, 23.2, 18.0; IR (neat) 3389 (O-H), 2926 (C-H),
1599, 1513, 1437, 1358, 1250, 1166, 1047, 819 cm-1; HREIMS, 70 eV,
m/z 296.1414 (calcd for C19H20O3 296.1412).
(E)-3,5-Dihydroxy-40-triisopropylsilyloxystilbene (20). To a
solution of 17 (0.473 g, 1.0 mmol) in MeOH (5 mL) was added
concentrated HCl (1.0 mL), and the reaction mixture was stirred at
room temperature for 10 h. The reaction was diluted with saturated
NaHCO3 solution (30 mL) and extracted with EtOAc (3 ꢀ 30 mL).
Removal of solvent at reduced pressure left an oily residue, which was
then purified by CC on silica gel with hexane/EtOAc (4:1) to give 20
(0.308 g, 80%) as an oil: IR (neat) 3389 (O-H), 2946 (C-H), 1602,
Arahypin-5 (6). To the solution of 22 (0.045 g, 0.1 mmol) in THF
(10 mL) was added TBAF (0.2 mL, 0.2 mmol, 1.0 M in THF) at 0 °C,
and the mixture was stirred at room temperature for 3 h. The reaction
mixture was quenched by the addition of saturated NH4Cl solution
(30 mL) and extracted with EtOAc (3 ꢀ 30 mL). The organic layer was
washed with H2O (30 mL), dried over anhydrous Na2SO4, and
concentrated under reduced pressure. The residue was purified by
CC with hexane/EtOAc (5:1), yielding 6 (0.028 g, 95%) as an oil: IR
1
1510, 1270, 1156, 1007, 911 cm-1; H NMR (300 MHz, CDCl3) δ
(neat) 3412 (O-H), 1600, 1512, 1441, 1252, 1010, 819, 761 cm-1
;
7.33 (2H, d, J = 8.7 Hz), 6.97 (1H, d, J = 16.2 Hz), 6.84 (2H, d, J = 8.7
Hz), 6.79 (1H, d, J = 16.2 Hz), 6.52 (2H, d, J = 2.1 Hz), 6.23 (1H, t, J =
2.1 Hz), 1.30-1.22 (3H, m), 1.09 (18H, d, J = 7.2 Hz); 13C NMR (75
MHz, CDCl3) δ 156.7, 156.7, 156.0, 140.4, 130.0, 129.2, 127.8, 127.8,
125.8, 120.1, 120.1, 106.0, 106.0, 101.9, 17.9 (6 carbons), 12.6 (3
carbons); HREIMS, 70 eV, m/z 384.2118 (calcd for C23H32O3Si
384.2121).
1H NMR (300 MHz, CD3OD) δ 7.35 (2H, d, J = 8.7 Hz), 6.96 (1H, d,
J = 16.2 Hz), 6.80 (1H, s), 6.78 (2H, d, J = 8.7 Hz), 6.64 (1H, d, J = 9.9
Hz), 6.51 (1H, s), 6.46 (1H, s), 5.57 (1H, d, J = 9.9 Hz), 1.40 (6H, s);
13C NMR (75 MHz, CD3OD) δ 158.4, 155.4, 154.5, 140.4, 130.5,
129.5, 129.3, 129.0, 129.0, 126.9, 118.3, 116.6, 116.6, 110.4, 106.9,
106.7, 76.9, 28.2, 28.2; HREIMS, 70 eV, m/z 294.1256 (calcd for
C19H18O3 294.1256).
(E)-3,5-Dihydroxy-2-{(E)-3-methylbut-1-enyl)}-40-triiso-
propylsilyloxystilbene (21). To a solution of 20 (0.154 g, 0.4 mmol)
and isovaleraldehyde (0.043 g, 0.5 mmol) in benzene (20 mL) was added
ethylenediamine diacetate (14 mg, 0.08 mmol) at room temperature. The
reaction mixture was refluxed for 10 h and then cooled to room
temperature. Evaporation of solvent and CC on silica gel using hexane/
ethylacetate (5:1) gave 21 (0.094 g, 52%) as an oil: 1H NMR (300 MHz,
CDCl3) δ 7.34 (2H, d, J = 8.7 Hz), 7.32 (1H, br s), 6.97 (1H, d, J =
16.2 Hz), 6.86 (2H, d, J = 8.7 Hz), 6.78 (1H, d, J = 16.2 Hz), 6.60 (2H, s),
6.31 (1H, d, J = 16.5 Hz), 6.13 (1H, dd, J = 16.5, 6.6 Hz), 5.30 (1H, br s),
2.60-2.48 (1H, m), 1.30-1.22 (3H, m), 1.14-1.09 (24H, m); 13C NMR
(75 MHz, CDCl3) δ 156.0, 153.8, 153.8, 145,5, 130.1, 128.8, 128.3, 127.7,
127.7, 125.8, 120.1, 120.1, 117.4, 111.3, 105.5, 105.5, 32.3, 22.4, 22.4, 17.9
(6 carbons), 12.6 (3 carbons); IR (neat) 3422 (O-H), 2945 (C-H),
’ ASSOCIATED CONTENT
1
Supporting Information. Copies of H and 13C NMR
S
b
spectra for compounds 2-6, 11-14, and 17-22. This informa-
tion can be accessed free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Tel: þ82-53-810-2529. Fax: þ82-53-810-4631. E-mail: yrlee@
yu.ac.kr.
648
dx.doi.org/10.1021/np100696f |J. Nat. Prod. 2011, 74, 644–649

Journal of Natural Products
ARTICLE
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This work was supported by grant no. RTI04-01-04 from the
Regional Technology Innovation Program of the Ministry of
Knowledge Economy (MKE).
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