Q. Shen et al. / Bioorg. Med. Chem. 22 (2014) 2671–2677
2675
J = 2.10 Hz, H-4), 6.34 (1H, d, J = 2.10 Hz, H-2), 5.50 (1H, tq, J = 6.71,
1.24 Hz, H-20), 4.60 (2H, d, J = 6.71, H-10), 4.01 (6H, s, OCH3), 1.83
(3H, s, CH3), 1.77 (3H, s, CH3); 13C NMR (400 MHz, CDCl3) d 180.3
(C, C-9), 165.9 (C, C-3), 163.4 (C, C-1), 157.8 (C, C-6), 156.6 (C,
C-4a), 139.2 (C, C-30), 136.3 (C, C-5), 121.5 (CH, C-8), 118.6
(CH, C-20), 115.4 (C, C-8a), 108.6 (CH, C-7), 103.3 (C, C-9a),
97.9 (CH, C-2), 93.6 (CH, C-4), 65.5 (CH2, C-10), 61.6 (CH3, OCH3),
56.4 (CH3, OCH3), 25.8 (CH3, C-40), 18.3 (CH3, C-50); MS (ESI) m/z:
357.1 [M+H]+, 379.1 [M+Na]+; ESI-HRMS (M+H+) for C20H21O6
expected 357.1333, found 357.1339.
(CH, C-2) 61.4 (CH3, OCH3), 56.5 (CH3, OCH3), 56.3 (CH3, OCH3), 44.3
(C, C-40), 25.6 (CH3, C-60), 21.3 (CH3, C-70), 14.3 (CH3, C-80); MS (ESI)
m/z: 371.4 [M+H]+, 393.4 [M+Na]+; ESI-HRMS (M+H+) for C21H23O6
expected 371.1489, found 371.1486.
4.3.8. 1-Hydroxy-5,6-dimethoxy-40,50-dihydro-40,40,50-
trimethylfurano[20,30:2,3]xanthone (100) and 1-hydroxy-5,6-
dimethoxy-40,50-dihydro-40,40,50-trimethylfurano [20,30:3,4]
xanthone (1000)
Compound 4 (0.10 g, 0.281 mmol) and water (20 mL) were
heated to 180 °C in an autoclave. The mixture was stirred for 2 h
and cooled to room temperature. Then, the organic layer was ex-
tracted with EtOAc. The combined organic layer was washed with
H2O, dried (Na2SO4), and concentrated under vacuum. The crude
product was purified by chromatography on silica gel (petroleum
ether/EtOAc, 4:1) to yield 100 as a yellow solid (0.041 g, 41%). 1H
NMR (300 MHz, CDCl3) d 13.09 (1H, s, OH), 7.96 (1H, d, J = 8.8 Hz,
H-8), 6.96 (1H, d, J = 8.8 Hz, H-7), 6.39 (1H, s, H-4), 4.50 (1H, q,
J = 6.4 Hz, H-50), 3.99 (3H, s, OCH3), 3.98 (3H, s, OCH3), 1.50 (3H,
s, H-70), 1.39 (3H, d, J = 6.4 Hz, H-60), 1.25 (3H, s, H-80); 13C NMR
(400 MHz, CDCl3) d 180.5 (C, C-9), 165.9 (C, C-3), 158.7 (C, C-1),
157.9 (C, C-6), 151.4 (C, C-4a), 150.2 (C, C-10a), 136.2 (C, C-5),
121.3 (CH, C-8), 116.9 (C, C-8a), 115.4 (C, C-2), 108.5 (CH, C-7),
103.7 (C, C-9a), 91.0 (CH, C-50), 89.8 (C, C-4), 61.4 (CH3, OCH3),
56.3 (CH3, OCH3), 43.3 (C, C-40), 25.2 (CH3, C-60), 20.6 (CH3, C-70),
14.3 (CH3, C-80); MS (ESI) m/z: 355.4 [MꢀH]ꢀ, 357.3 [M+H]+;
ESI-HRMS (M+H+) for C20H21O6 expected 357.1333, found
357.1319. The above procedure also yielded 1000 as a yellow solid
(0.034 g, 34%). 1H NMR (300 MHz, CDCl3) d 13.20 (1H, s, OH),
7.91 (1H, d, J = 8.8 Hz, H-8), 7.22 (1H, d, J = 8.8 Hz, H-7), 6.16 (1H,
s, H-2), 4.54 (1H, q, J = 6.4 Hz, H-50), 4.05 (3H, s OCH3), 3.97 (3H,
s, OCH3), 1.63 (3H, s, H-70), 1.42 (3H, d, J = 6.4 Hz,H-60), 1.34 (3H,
s, H-80); 13C NMR (400 MHz, CDCl3) d 180.1(C, C-9), 166.2 (C, C-
3), 164.3 (C, C-1), 157.9 (C, C-6), 152.8 (C, C-4a), 150.1 (C, C-10a),
136.3 (C, C-5), 121.7 (C, C-8), 115.4 (C, C-8a), 113 (C, C-4), 108.5
(C, C-7), 103.3 (C, C-9a), 93.9 (CH, C-2), 90.9 (CH, C-50) 61.5 (CH3,
OCH3), 56.4 (CH3, OCH3), 43.7 (C, C-40), 25.6 (CH3, C-60), 21.4
(CH3, C-70), 14.2 (CH3, C-80); MS (ESI) m/z: 357.4 [M+H]+, 735.0
[2M+Na]+.
4.3.5. 1,5,6-Trimethoxy-3-(30-methylbut-20-enyloxy)-9H-
xanthen-9-one (10)
A solution of 4 (1.61 g, 4.52 mmol) in DMSO (20 mL) was stirred
at 10 °C. Then, NaH (1.01 g, 45.18 mmol) was added in portions.
The mixture was cooled to 0 °C, and then Me2SO4 (4.29 mL,
45.18 mmol) was added. After 1.5 h, the solution was slowly
poured into ice-water (200 mL), and the precipitated product was
collected by filtration to obtain 10 as a yellowish solid (1.64 g,
98%). 1H NMR (300 MHz, CDCl3) d 8.03 (1H, d, J = 9.03 Hz, H-8),
6.95 (1H, d, J = 9.03 Hz, H-7), 6.61 (1H, d, J = 2.29 Hz, H-4), 6.36
(1H, d, J = 2.29 Hz, H-2), 5.53 (1H, tq, J = 6.71 Hz, 1.24 Hz, H-20),
4.62 (2H, d, J = 6.71, H-10), 4.02 (3H, s, OCH3), 3.99 (3H, s, OCH3),
3.95 (3H, s, OCH3), 1.83 (3H, s, CH3), 1.78 (3H, s, CH3); 13C NMR
(400 MHz, CDCl3) d 174.9 (C, C-9), 164.1 (C, C-3), 161.9 (C, C-1),
159.8 (C, C-6), 156.6 (C, C-4a), 149.3 (C, C-10a), 139.5 (C, C-30),
135.8 (C, C-5), 122.2 (C, C-8), 118.5 (C, C-8a), 118.0 (CH, C-20),
108.3 (CH, C-7), 106.8 (C, C-9a), 95.9 (CH, C-2), 93.7 (CH, C-4),
65.4 (CH2, C-10), 61.5 (CH3, OCH3), 56.3 (2ꢁ CH3, OCH3), 25.8
(CH3, C-40), 18.2 (CH3, C-50); MS (ESI) m/z: 393.3 [M+Na]+, 763.4
[2M+Na]+; ESI-HRMS (M+H+) for C21H23O6 expected 371.1489,
found 371.1467.
4.3.6. 3-(Benzyloxy)-1,5,6-trimethoxy-9H-xanthen-9-one (110)
Compound 10 (0.060 g, 0.162 mmol) and mesitylene (5 mL)
were refluxed for 12 h. After filtration, BnBr (0.055 g, 0.324 mmol),
K2CO3 (0.045 g, 0.324 mmol), and DMF (5 mL) were added, and the
mixture was stirred for 2 h and cooled to room temperature. The
organic layer was extracted with EtOAc. The combined organic
layer was washed with H2O, dried (Na2SO4), and concentrated un-
der vacuum to give the crude product, which was purified by chro-
matography on silica gel (petroleum ether/EtOAc, 1:2) to yield 110
as a yellowish solid (0.047 g, 74%). 1H NMR (300 MHz, CDCl3) d 8.03
(1H, d, J = 9.05 Hz, H-7/H-8), 7.34–7.50 (5H, m, 5ꢁ Ar-H), 6.95 (1H,
d, J = 9.05 Hz, H-7/H-8), 6.69 (1H, d, J = 2.12 Hz, H-2/H-4), 6.44 (1H,
d, J = 2.12 Hz, H-2/H-4), 5.16 (2H, s, OCH2Ph), 4.01 (3H, s, OCH3),
3.99 (3H, s, OCH3), 3.96 (3H, s, OCH3), ESI-HRMS (M+H+) for
4.3.9. 1,5,6-Trimethoxy-4-(20-methylbut-30-en-20-yl)-9-oxo-9H-
xanthen-3-yl acetate (11)
A mixture of 10 (0.50 g, 1.35 mmol) and anhydrous sodium ace-
tate (0.22 g, 2.70 mmol) in acetic anhydride (50 mL) was heated to
185 °C in an autoclave. The mixture was stirred for 2 h and cooled
to room temperature. The solvent was removed under vacuum.
Purification by flash chromatography (petroleum ether/EtOAc,
1:2) afforded 11 as a yellowish solid (0.44 g, 79%). This was an
unstable compound. 1H NMR (300 MHz, CDCl3) d 8.02 (1H, d,
J = 8.9 Hz, H-7/H-8), 6.98 (1H, d, J = 8.9 Hz, H-7/H-8), 6.38 (1H,
dd, J = 17.55, 10.6 Hz, H-30), 6.37 (1H, s, H-2), 4.95 (1H, d,
J = 17.55 Hz, H-40a), 4.89 (1H, d, J = 10.6 Hz, H-40b), 4.00 (3H, s,
OCH3), 3.96 (3H, s, OCH3), 3.95 (3H, s, OCH3), 2.26 (3H, sCOCH3),
1.72 (6H, s, CH3), ESI-HRMS (M+H+) for C23H24O7 expected
413.1595, found 413.1595.
C23H20O6 expected 393.1333, found 393.1330.
4.3.7. 1,5,6-Trimethoxy-40,50-dihydro-4040,50-trimethylfurano
[20,30:3,4]xanthone (1100)
Compound 10 (0.060 g, 1.62 mmol) and water (20 mL) were
heated to 180 °C in an autoclave. The mixture was stirred for 2 h
and cooled to room temperature. Then, the organic layer was ex-
tracted with EtOAc. The combined organic layer was washed with
H2O, dried (Na2SO4), and concentrated under vacuum to give the
crude product, which was purified by chromatography on silica
gel (petroleum ether/EtOAc, 1:2) to yield 1100 as a yellowish solid
(0.049 g, 82%). 1H NMR (400 MHz, CDCl3) d 8.02 (1H, d, J = 8.8 Hz,
H-8), 6.93 (1H, d, J = 8.8 Hz, H-7), 6.30 (1H, s, H-2), 4.56 (1H, q,
J = 6.4 Hz, H-50), 3.98 (3H, s, OCH3), 3.97 (3H, s, OCH3), 3.95 (3H,
s, OCH3), 1.63 (3H, s, H-70), 1.43 (3H, s, H-80), 1.43 (3H, d,
J = 6.4 Hz, H-60); 13C NMR (400 MHz, CDCl3) d 175(C, C-9), 164.3
(C, C-3), 162.8 (C, C-1), 156.8 (C, C-6), 155.1 (C, C-4a), 149.1
(C, C-10a), 135.9 (C, C-5), 122.4 (C, C-8), 118.0 (C, C-8a), 114.1 (C,
C-4), 108.2 (CH, C-7), 106.7 (C, C-9a), 90.9 (CH, C-50), 90.4
4.3.10. 3-Hydroxy-1,5,6-trimethoxy-4-(20-methylbut-30-en-20-
yl)-9H-xanthen-9-one (3)
A solution of 11 (0.44 g, 1.08 mmol) in MeOH (20 mL) was stir-
red at room temperature. Then, H2O (20 mL) and NaOH (0.095 g,
2.38 mmol) were added. The mixture was stirred at room temper-
ature for 2 h. The mixture was acidified carefully with 0.5 M HCl
and extracted with EtOAc. The combined organic layer was washed
with H2O, dried (Na2SO4), and concentrated under vacuum to give
unstable 3, which was quickly used in the next step.