Journal of Natural Products
Article
mL). The aqueous solution was extracted with CHCl3 (70 mL) twice.
The organic layer was dried over anhydrous Na2SO4. The organic
solvent was evaporated to dryness in vacuo and subjected to silica gel
column chromatography using hexanes−EtOAc (8:2 then 7:3).
Fractions containing the product were pooled and dried to give the
title compound (710 mg, 81%).
completion, the mixture was passed through a Celite column, and the
pass-through solution was dried and subjected to silica gel column
chromatography using CHCl3−MeOH (9:1) as eluent. Fractions
containing the product were pooled and dried to afford the title
compound (35 mg, 83%).
Compound ( )-8: brownish, fluffy powder, [α]22D 0 (c 1, MeOH);
1H NMR (500 MHz, acetone-d6) δ 12.37 (1H, s, OH), 6.59 (1H, d, J
1
Compound 5: yellow oil; H NMR (500 MHz, acetone-d6) δ 7.73
(1H, d, J = 16.5 Hz), 7.55 (1H, d, J = 8.8 Hz) 7.52−7.18 (24H, m),
7.13 (2H, m), 6.95 (1H, d, J = 8.8 Hz), 6.89 (1H, d, J = 16.5 Hz), 6.75
(1H, d, J = 8.8 Hz), 6.52 (2H, s), 5.15 (2H, s), 5.08 (4H, s), 5.05 (2H,
s), 4.87 (2H, s), 3.94 (3H, s); 13C NMR (125 MHz, acetone-d6) δ
194.5, 162.0, 158.4 (2C), 156.9, 152.7, 142.6, 140.3, 138.8, 138.1 (2C),
138.0, 137.9, 129.4 (2C), 129.3 (2C), 129.2 (3C), 129.2 (3C),
129.1(2C), 129.0 (2C), 128.8, 128.8, 128.7,128.7(2C), 128.5 (2C),
128.1 (4C), 123.5, 122.9, 113.8, 109.6, 94.5 (2C), 76.7, 75.8, 70.9
(2C), 70.9, 56.6; (+)-HRTOFESIMS m/z 769.3174 [M + H]+ (calcd
for C51H45O7, 769.3165).
= 8.5 Hz), 6.48 (1H, d, J = 8.5 Hz), 5.96 (1H, d, J = 2 Hz), 5.95 (1H,
d, J = 2 Hz), 4.64 (1H, t, J = 11 Hz), 4.48 (1H, dd, J = 11, 5.5 Hz),
4.28 (1H, dd, J = 10.5, 5.5 Hz), 3.80 (3H, s); 13C NMR (125 MHz,
acetone-d6) δ 198.0, 167.3, 165.4, 164.5, 148.6, 144.5, 134.5, 120.8,
116.1, 104.0, 103.5, 96.8, 95.7, 70.9, 56.3, 47.6; (+)-HRTOFESIMS m/
z 319.0813 (calcd for C16H15O7, 319.0818).
Synthesis of 5-Hydroxy-3-(4-methoxy-2,3-bis-
(methoxymethoxy)phenyl)-7-(methoxymethoxy)chroman-4-
one (9). Compound ( )-8 (25 mg, 0.078 mmol) was dissolved in
CH2Cl2 (1.5 mL); then N,N-diisopropylethylamine (82 μL, 0.46
mmol) was added to the mixture at 0 °C. The reaction mixture was left
stirring at room temperature (rt) for 30 min, and subsequently
MOMCl (22 μL, 0.273 mmol) was added. The reaction was stirred at
0 °C for 2 h, then left to come to rt. The reaction was quenched with
potassium phosphate buffer pH 7.0, diluted with ddH2O (8 mL), and
extracted with EtOAc (10 mL) twice. The organic layer was washed
with brine solution twice and dried over anhydrous Na2SO4, and the
solvent was removed in vacuo. The crude material was subjected to
silica gel column chromatography using hexanes−EtOAc (7:3 then
6:4). Fractions containing the product were pooled and dried to afford
the title compound (32 mg, 91%).
Synthesis of 2-(2,3-Bis(benzyloxy)-4-methoxyphenyl)-3,3-
dimethoxy-1-(2,4,6-tris(benzyloxy)phenyl)propan-1-one (6).
To a solution of 5 (500 mg, 0.65 mmol) in MeOH−CH2Cl2 (9:1)
(6.50 mL) was added Tl(NO3)3·3H2O (578 mg, 1.30 mmol). The
reaction mixture was stirred at 30−40 °C for 4 h. Upon a complete
conversion of the starting material to the product, the reaction was
brought to 0 °C, then a 10% solution of Na2SO3 (5 mL) and 2%
HCl(aq) (2 mL) were added. The reaction was stirred for another 30
min at the same temperature. The reaction was diluted with ddH2O
(50 mL), extracted with CHCl3 (60 mL) twice, washed with brine
solution twice, and dried over anhydrous Na2SO4. The organic solvent
was evaporated to dryness, then subjected to silica gel column
chromatography using hexanes−EtOAc (10:2 then 7:3). Fractions
containing the product were pooled and dried to give the title
compound (390 mg, 72%).
Compound 9: colorless solid; 1H NMR (500 MHz, CDCl3) δ 12.11
(1H, s, OH), 6.82 (1H, d, J = 8.6 Hz), 6.70 (1H, d, J = 8.6 Hz), 6.20
(1H, d, J = 2 Hz), 6.14 (1H, d, J = 2 Hz), 5.18 (2H, s), 5.14 (2H, s),
5.11 (2H, d, J = 2 Hz), 4.53−4.48 (3H, m), 3.84 (3H, s), 3.59 (3H, s),
3.50 (3H, s), 3.48 (3H, s); 13C NMR (125 MHz, CDCl3) δ 197.6,
165.3, 164.3, 163.2, 153.5, 150.0, 138.6, 124.3, 121.1, 106.1, 104.3,
99.9, 98.7, 97.0, 95.5, 94.0, 71.2, 57.8, 57.5, 56.5, 56.0, 45.8;
(+)-HRTOFESIMS m/z 451.1604 (calcd for C22H27O10, 451.1604).
Synthesis of (E)-5-((3,7-Dimethylocta-2,6-dien-1-yl)oxy)-3-
(4-methoxy-2, 3-bis(methoxymethoxy)phenyl)-7-
(methoxymethoxy)chroman-4-one (10). To a solution of 9 (15
mg, 0.033 mmol) in DMF (0.35 mL) was added K2CO3 (9 mg, 0.066
mmol), and the reaction mixture was stirred for 30 min at room
temperature. Subsequently, geranyl bromide (9.2 μL, 0.04 mmol) was
added to the reaction mixture and stirred for another 3 h until
complete consumption of the starting material as judged by TLC. The
reaction was then quenched with potassium phosphate buffer pH 7.0
and extracted with EtOAc twice. The EtOAc layer was dried over
anhydrous Na2SO4; then the organic solvent was dried in vacuo. The
extract was subjected to silica gel column chromatography using
hexanes−EtOAc (7:3) as mobile phase. Fractions containing the
product were pooled and dried under vacuum to give the title
compound (18 mg, 91%).
1
Compound 6: yellowish oil; H NMR (500 MHz, acetone-d6) δ
7.39−7.23 (25H, m), 6.96 (1H, d, J = 8.8 Hz), 6.45 (1H, d, J = 8.8
Hz), 6.27 (2H, s), 5.32 (1H, d, J = 8.5 Hz), 5.16 (1H, d, J = 8.5 Hz),
5.04 (2H, s), 4.90 (1H, d, J = 8.5 Hz), 4.92 (2H, s), 4.82 (2H, q, J = 12
Hz), 4.31 (1H, d, J = 8.5 Hz), 3.73 (3H, s), 3.31 (3H, s), 3.08 (3H, s);
13C NMR (125 MHz, acetone-d6) δ 197.5, 161.3, 157.4 (2C), 153.0,
151.4, 141.3, 138.3, 138.0, 137.1(2C), 136.9, 128.4 (2C), 128.2 (2C),
128.1(4C), 128.1 (2C), 128.0 (2C),127.8, 127.7 (2C), 127.6, 127.4
(2C), 127.3, 127.1 (2C), 127.0 (4C), 125.0, 120.6, 113.9, 107.5, 104.5,
93.0 (2C), 74.7, 74.3, 69.9, 69.8 (2C), 55.3, 54.3, 53.9, 51.2;
(+)-HRTOFESIMS m/z 853.3358 (calcd for C53H50NaO9, 853.3353).
Synthesis of 5,7-Bis(benzyloxy)-3-(2,3-bis(benzyloxy)-4-me-
thoxyphenyl)-4H-chromen-4-one (7). To a solution of 6 (350 mg,
0.42 mmol) in AcOH (20 mL) was added a mixture of AcOH−12 N
HCl (5:1) (20 mL). The mixture was stirred for 5 min, then left to
stand at room temperature for 1 h, at which time the reaction mixture
was cooled and ddH2O (50 mL) was added. The mixture was brought
to 60 °C for 30 min, then extracted with CHCl3 (100 mL) twice. The
CHCl3 layer was washed three times with brine solution and then
dried over anhydrous Na2SO4. The organic layer was evaporated to
dryness, then subjected to silica gel column chromatography using
hexanes−EtOAc (10:2 then 7:3). Fractions containing the product
were pooled and dried to give the title compound (208 mg, 73%).
Compound 10: colorless solid; 1H NMR (500 MHz, CDCl3) δ 6.82
(1H, d, J = 8.6 Hz), 6.66 (1H, d, J = 8.6 Hz), 6.25 (1H, d, J = 2 Hz),
6.19 (1H, d, J = 2 Hz), 5.51 (1H, t, J = 6 Hz), 5.20−5.17 (3H, m),
5.13−5.04 (4H, m), 4.61 (1H, t-like m), 5.50 (1H, m), 4.42 (1H, m),
3.81 (3H, s), 3.58 (3H, s), 3.52 (3H, s), 3.49 (3H, s), 2.10−2.01 (4H,
m), 1.70 (3H, s), 1.65 (3H, s), 1.58 (3H, s); 13C NMR (125 MHz,
CDCl3) δ 190.0, 164.9, 163.1, 161.9, 152.9, 149.8, 140.4, 138.6, 131.7,
124.5, 123.9, 122.5, 119.4, 108.1, 107.6, 99.9, 98.7, 95.1, 95.04, 94.1,
71.3, 66.3, 57.8, 57.4, 56.5, 56.0, 46.8, 39.5, 26.3, 25.7, 17.7, 16.8;
(+)-HRTOFESIMS m/z 609.2672 (calcd for C32H42NaO10,
609.2672).
Synthesis of (E)- and (Z)-8-(3,7-Dimethylocta-2,6-dien-1-yl)-
5-hydroxy-3-(4-methoxy-2,3-bis(methoxymethoxy)phenyl)-7-
(methoxymethoxy)chroman-4-one (11). To a solution of 10 (11
mg, 0.018 mmol) in chlorobenzene (300 μL) was added Eu(fod)3 (2
mg, 0.0018 mmol) and NaHCO3 (1.57 mg, 0.018 mmol). The mixture
was stirred at 85 °C for 24 h; then the reaction mixture was filtered
over Celite and the solvent was evaporated in vacuo. The residue was
subjected to silica gel column chromatography using hexanes−EtOAc
1
Compound 7: yellowish oil; H NMR (500 MHz, acetone-d6) δ
8.59 (1H, s), 7.47−7.12 (20H, m), 6.78 (1H, d, J = 8.5 Hz), 6.59 (1H,
d, J = 8.5 Hz), 6.30 (2H, s), 5.17−5.05 (2H, m), 4.79 (2H, s), 4.90
(2H, s), 4.82 (2H, s), 3.81 (3H, s); 13C NMR (125 MHz, acetone-d6)
δ 187.5, 162.3, 158.2, 154.2, 151.8, 142.4, 139.0, 138.4, 138.0 (2C),
137.7, 129.3, 129.3 (2C), 129.2 (3C), 129.2, 129.1, 129.0, 128.9, 128.8
(2C), 128.7, 128.6 (3C), 128.5, 128.4,128.4, 127.6 (3C), 123.0, 115.8,
109.9, 108.3, 93.8 (2C), 75.7, 75.6, 70.7 (2C), 56.3; (+)-HRTOFE-
SIMS m/z 677.2534 (calcd for C44H37O7, 677.2536).
Synthesis of ( )-3-(2,3-Dihydroxy-4-methoxyphenyl)-5,7-
dihydroxychroman-4-one (( )-8). Compound 7 (90 mg, 0.133
mmol) was dissolved in EtOH−EtOAc (1:1) (5 mL); then Pd/C 10%
(40 mg) was added. The mixture was degassed under vacuum, and
then hydrogen gas was applied. The reaction mixture was stirred for 3
h, during which TLC was used to monitor the reaction. Upon
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J. Nat. Prod. XXXX, XXX, XXX−XXX