Journal of Natural Products
Article
m), 2.03 (3H, s), 1.98 (3H, s), 1.97 (3H, s), 1.96 (3H, s); 13C NMR
(75 MHz, DMSO) δ 170.5, 170.0, 169.8, 169.7, 154.8, 150.0, 137.9,
133.8, 104.6, 102.2, 101.6, 72.2, 71.6, 70.8, 68.7, 62.3, 58.5, 21.0, 20.9,
20.8, 20.7; HRESIMS m/z 509.1267 [M + Na]+ (calcd for
C21H26O13Na, 509.1266).
132.9, 130.4, 130.2, 129.8, 124.5, 119.7, 113.7, 112.1, 99.9, 73.2, 71.9,
71.7, 68.4, 61.7, 60.4, 29.7, 25.9, 25.6, 20.8, 20.6, 20.5, 20.5, 18.4, 18.2,
18.1, −3.8, −4.3, −4.4, −4.5; HRESIMS m/z 917.4344 [M + H]+
(calcd for C46H73O13Si3, 917.4353).
trans-2,3,5,4′-Tetrahydroxystilbene 2-O-β-D-Glucoside Ace-
tate (2′a). A mixture of compound 3′a (1.0 g, 1.51 mmol), anhydrous
THF (20 mL), and TBAF (1.0 M solution in THF, 4.25 mL) was
stirred at 0 °C for 1.5 h. The reaction was quenched with ice cold 6 N
HCl (6.77 mL), and the mixture was extracted with EtOAc (4 × 50
mL). The combined organic layer was dried over MgSO4 and
evaporated in vacuo to give a residue, which was purified by column
chromatography (1:1 EtOAc−n-hexanes) to give compound 2′a (0.62
2,3,5-Trihydroxybenzaldehyde 1-O-β-D-Glucoside Acetate
(5′). A mixture of compound 6′ (8.0 g, 16.4 mmol), pyridinium
dichromate (4.26 g, 1.5 equiv), and anhydrous CH2Cl2 (150 mL) was
stirred at room temperature for 12 h. To the resulting mixture was
added a sufficient amount of Celite to absorb the reaction mixture,
which then was vigorously stirred until the reaction was complete. The
resulting paste was transferred directly to the top of a column of silica
gel and subsequently purified by flash column chromatography (1:3
1
g, 71%) as a solid: H NMR (300 MHz, DMSO-d6) δ 9.55 (1H, s,
1
EtOAc−n-hexanes) to afford 5′ (4.78 g, 60%): H NMR (300 MHz,
D2O exchangeable), 9.21 (1H, s, D2O exchangeable), 9.11 (s, 1H, D2O
exchangeable), 7.35 (d, J = 8.7 Hz, 2H), 7.32 (d, J = 16.5 Hz, 1H),
6.87 (1H, J = 16.5 Hz, d), 6.75 (2H, J = 8.7 Hz, d), 6.50 (1H, J = 2.7
Hz, d), 6.30 (1H, J = 2.7 Hz, d), 5.42−5.02 (4H, m), 4.19 (1H, J = 5.1,
4.8 Hz, dd), 4.04 (1H, J = 2.4, 2.4 Hz, dd), 3.80 (1H, m), 2.03 (3H, s),
1.99 (3H, s), 1.99 (3H, s), 1.89 (3H, s); 13C NMR (75 MHz, DMSO-
d6) δ 167.7, 167.4, 167.2, 167.1, 154.9, 152.2, 148.4, 132.6, 130.2,
126.3, 126.1, 125.5, 118.6, 113.3, 100.6, 99.2, 98.8, 69.7, 69.2, 68.1,
65.9, 59.7, 57.6, 18.4, 18.2, 18.1, 11.9; HRESIMS m/z 597.1580 [M +
Na]+ (calcd for C28H30O13Na, 597.1579).
CDCl3) δ 10.18 (1H, s), 7.27 (1H, s, D2O exchangeable), 6.81 (1H, J
= 3.0 Hz, d), 6.75 (1H, J = 3.0 Hz, d), 5.38−3.79 (8H, m, 1H D2O
exchangeable), 2.15 (3H, s), 2.11 (3H, s), 2.05 (3H, s), 2.04 (3H, s);
13C NMR (75 MHz, CDCl3) δ 190.3, 170.9, 170.4, 170.3, 169.8, 169.5,
169.4, 154.6, 150.9, 139.9, 130.0, 110.5, 105.6, 103.4, 72.5, 72.4, 71.5,
67.9, 61.4, 20.7, 20.6, 20.5, 20.5; HRESIMS m/z 483.1126 [M + H]+
(calcd for C21H23O13, 483.1133).
2-Hydroxy-3,5-bis(tert-butyldimethylsilanyloxy)-
benzaldehyde 1-O-β-D-Glucoside Acetate (4′). A solution of
compound 5′ (4.7 g, 9.7 mmol) and diisopropylethylamine (4.82 mL,
3 equiv) in dry CH2Cl2 (100 mL) was stirred at room temperature for
10 min. Then tert-butyldimethylsilyl chloride (4.39 g, 3 equiv) was
added in portions, and the mixture was stirred for an additional 15 h.
The reaction was quenched with H2O (50 mL) and extracted with
CH2Cl2 (3 × 50 mL). The combined organic layer was evaporated
under reduced pressure to give a crude product, which was purified by
flash chromatography (1:3 EtOAc−n-hexanes) to afford 4′ (6.2 g,
90%): 1H NMR (300 MHz, CDCl3) δ 10.27 (1H, s), 6.90 (1H, J = 2.7
Hz, d), 6.60 (1H, J = 2.7 Hz, d), 5.34−3.60 (7H, m), 2.07 (3H, s),
2.03(3H, s), 2.01 (3H, s), 1.99 (3H, s), 1.03 (9H, s), 0.97 (9H, s), 0.28
(6H, s), 0.19 (6H, s); 13C NMR (75 MHz, CDCl3) δ 190.0, 170.6,
170.3, 169.3, 169.2, 152.8, 148.9, 142.3, 131.9, 118.4, 110.4, 99.1, 72.9,
71.9, 71.6, 68.3, 61.25, 25.9, 25.6, 20.8, 20.6, 20.5, 20.5, 18.1, 17.4,
−4.0, −4.2, −4.5; HRESIMS m/z 735.2835 [M + Na]+ (calcd for
C33H52O13NaSi2, 735.2839).
cis-2,3,5,4′-Tetrahydroxystilbene 2-O-β-D-Glucoside Acetate
(2′b). The title compound was obtained in 73% overall yield from
compound 3′b in a manner similar to that described for the
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preparation of 2′b: H NMR (300 MHz, DMSO-d6) δ 9.46, 9.00,
8.96 (1H, s each, D2O exchangeable), 7.04 (2H, J = 8.7 Hz, d), 6.62
(2H, J = 8.7 Hz, d), 6.46 (1H, J = 12.3 Hz, d), 6.41 (1H, J = 12.3 Hz,
d), 6.23 (1H, J = 2.7 Hz, d), 6.00 (1H, J = 2.7 Hz, d), 5.38−4.94 (4H,
m), 4.16−3.93 (3H, m), 2.54 (3H, s), 2.53 (3H, s), 2.52 (3H, s), 2.51
(3H, s); 13C NMR (75 MHz, DMSO-d6) δ 170.9, 170.2, 170.0, 169.9,
156.5, 154.2, 150.5, 134.8, 132.7, 130.4, 130.1, 128.1, 123.3, 114.5,
106.8, 102.3, 101.9, 72.8, 71.7, 68.4, 61.5, 19.5, 19.2, 19.1, 13.1;
HRESIMS m/z 597.1580 [M + Na]+ (calcd for C28H30O13Na,
597.1579).
4-(tert-Butyldimethylsilanyloxy)benzaldehyde (12). A solu-
tion of 4-hydroxybenzaldehyde (5.0 g, 40.9 mmol) and diisopropy-
lethylamine (10 mL, 1.5 equiv) in dry CH2Cl2 (100 mL) was stirred
for 10 min at room temperature. To the solution was added tert-
butyldimethylsilyl chloride (9.2 g, 1.5 equiv) in portions, and stirring
continued for 12 h. The reaction was quenched with H2O and
extracted with CH2Cl2 (3 × 30 mL), and the combined organic layer
was evaporated under reduced pressure to give a pale yellow oil, which
was purified by flash chromatography (1:3 EtOAc−n-hexane) to afford
2-Hydroxy-3,5,4′-tris(tert-butyldimethylsilanyloxy) 1-O-β-D-
Glucoside Acetate (3′a, 3′b). To a suspension of compound 14
(3.56 g, 6.3 mmol) in THF (50 mL) was added dropwise n-BuLi (1.6
M in hexane, 8.1 mL) at −78 °C, and the resulting mixture was stirred
at the same temperature for 30 min. The reaction was then warmed to
rt and stirred for an additional 1 h. The reaction mixture was recooled
to −78 °C and then was added to a solution of compound 4′ (3.0 g,
4.2 mmol) in THF (20 mL). Stirring was continued at −78 °C for 1 h,
then at rt for 18 h. The reaction was quenched with cold H2O (30 mL)
and extracted with EtOAc (3 × 10 mL). The combined organic layer
was dried over MgSO4 and evaporated in vacuo to give a residue,
which was purified by flash column chromatography over silica gel
(1:10 EtOAc−n-hexane) to afford 3′a (750 mg, 20%) as a pale yellow
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12 (8.8 g, 92%): H NMR (300 MHz, CDCl3) δ 9.90 (1H, s), 7.80
(2H, J = 8.7 Hz, d), 6.96 (2H, J = 8.7 Hz, d), 1.00 (9H, s), 0.26 (6H,
s); 13C NMR (75 MHz, CDCl3) δ 191.0, 161.6, 132.3, 131.9, 130.4,
120.5, 115.6, 25.6, 25.5, 18.2, −4.4; HRESIMS m/z 237.1294 [M +
H]+ (calcd for C13H20O2Si, 237.1305).
[4-(tert-Butyldimethylsilanyloxy)phenyl]methanol (13). A
mixture of compound 12 (5.0 g, 21.15 mmol), NaBH4 (800 mg,
21.15 mmol), and MeOH (100 mL) was stirred at rt for 30 min. The
reaction was quenched with dilute aqueous HCl and extracted with
CH2Cl2 (3 × 10 mL). The combined organic layer was dried over
anhydrous MgSO4 and then evaporated in vacuo to give a residue,
which was purified by flash column chromatography over silica gel (1:3
EtOAc−n-hexane) to afford 13 (4.73 g, 94%) as a colorless liquid: 1H
NMR (300 MHz, CDCl3) δ 7.22 (2H, J = 8.4 Hz, d), 6.84 (2H, J = 8.4
Hz, d), 4.58 (2H, s), 2.19 (1H, s, D2O exchangeable), 1.00 (9H, s),
0.21 (6H, s); 13C NMR (75 MHz, CDCl3) δ 155.2, 133.7, 128.6,
120.1, 64.96, 25.7, −4.4.
[4-(tert-Butyldimethylsilanyloxy)phenyl]methyltriphenyl-
phosphonium Bromide (14). Compound 13 (4.5 g, 18.87 mmol)
was treated with PPh3 (2.2 equiv) and CBr4 (4.4 equiv) in Et2O to
afford the crude benzyl bromide (82% yield), which was used for the
next step without further purification. The product was dissolved in
toluene (35 mL), Ph3P (6.97 g, 26.56 mmol) was added, and the
reaction mixture was refluxed for 12 h under N2. The corresponding
phosphonium salt (14) precipitated as a white solid during the
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solid and 3′b (1.5 g, 40%) as a pale yellow solid. For 3′a: H NMR
(300 MHz, CDCl3) δ 7.40 (2H, J = 8.7 Hz, d), 7.21 (1H, J = 16.5 Hz,
d), 6.88 (1H, J = 16.5 Hz, d), 6.81 (2H, J = 8.7 Hz, d), 6.67 (1H, J =
2.7 Hz, d), 6.25 (1H, J = 2.7 Hz, d), 5.34−3.56 (7H, m), 2.02 (3H, s),
2.01 (3H, s), 1.99 (3H, s), 1.90 (3H, s), 1.01 (9H, s), 0.99 (9H, s),
0.98 (9H, s), 0.26 (6H, s), 0.21 (6H, s), 0.19 (6H, s); 13C NMR (75
MHz, CDCl3) δ 171.0, 170.7, 169.8, 169.7, 156.0, 152.6, 149.2, 138.6,
133.3, 131.3, 129.8, 128.3, 121.8, 120.7, 112.1, 109.7, 100.4, 73.7, 72.4,
72.2, 68.7, 61.9, 30.1, 26.3, 26.1, 26.0, 23.7, 21.2, 21.0, 20.9, 20.8, 18.8,
18.6, 18.5, 14.5, −3.8, −3.8, −3.9, −3.9; HRESIMS m/z 917.4344 [M
+ H]+ (calcd for C46H73O13Si3, 917.4353).
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For 3′b: H NMR (300 MHz, CDCl3) δ 7.00 (2H, J = 6.3 Hz, d),
6.64 (2H, J = 6.3 Hz, d), 6.52 (1H, J = 12.3 Hz, d), 6.47 (1H, J = 12.3
Hz, d), 6.50 (2H, J = 3.6 Hz, d), 5.28−5.10 (4H, m), 4.20 (1H, J = 4.2,
3.9 Hz, dd), 4.11 (1H, J = 2.4, 2.4 Hz, dd), 3.53 (1H, octet), 2.05 (3H,
s), 2.02 (3H, s), 1.99 (3H, s), 1.95 (3H, s), 1.03 (9H, s), 0.97 (9H, s),
0.89 (9H, s), 0.22 (6H, s), 0.18 (6H, s), 0.02 (6H, s); 13C NMR (75
MHz, CDCl3) δ 170.6, 170.4, 169.4, 169.3, 154.8, 152.0, 148.9, 138.5,
G
J. Nat. Prod. XXXX, XXX, XXX−XXX