C.-R. Su et al. / Bioorg. Med. Chem. 17 (2009) 6137–6143
6141
s, OCH3-5), 2.70 (2H, s, H-7), 1.93 (2H, q, J = 7.5 Hz, H-20), 1.59 (6H,
s, (CH3)2-10), 1.48 (6H, s, (CH3)2-8), 0.72 (3H, t, J = 7.5 Hz, H-30); 13C
NMR (CDCl3, 75 MHz) d: 190.4, 162.6, 159.7, 158.1, 156.9, 139.2,
119.3, 112.4, 111.5, 108.5, 79.5, 63.4, 49.7, 40.6, 35.0, 30.5 (2ꢀ),
26.3 (2ꢀ), 10.1; EIMS m/z (rel. int.%): 344 (M+, 20), 315 (68), 259
(100); HR-EIMS m/z 344.1624 (calcd for C20H24O5: 344.1624); Anal.
(C20H24O5) C, H.
100.9, 75.7, 62.0, 31.8, 26.7 (2ꢀ), 17.0; EIMS m/z (rel. int.%): 260
(M+, 45), 205 (100); HR-EIMS m/z 260.1046 (calcd for C15H16O4:
260.1049); Anal. (C15H16O4) C, H.
4.4. General procedure for compounds 7, 11, and 16
To a solution of corresponding coumarin (1 mmol) in acetone
(20 mL) was added K2CO3 (830 mg, 6 mmol) and CH3I (283.9 mg,
2 mmol). After 3 h stirring at the refluxing temperature, the reac-
tion mixture was extracted with EtOAc, washed with water, dried
over Na2SO4, evaporated and the obtained residue was purified by
column chromatography over silica gel for each compound.
4.3.3. 10-(1,1-Dimethylpropyl)-5-hydroxy-8,8-dimethyl-7,8-
dihydro-6H-pyrano[3,2-c]chromen-2-one (10)
87.6 mg(87.8%), mp195–196 °C; 1HNMR(CDCl3, 300 MHz)d:8.09
(1H, d, J = 9.6 Hz, H-4), 6.24 (1H, br s, D2O-exchangeable, OH-5), 6.11
(1H, d, J = 9.6 Hz, H-3), 2.69 (2H, t, J = 7.0 Hz, H-6), 1.90 (3H, q,
J = 7.4 Hz, H-20), 1.81 (2H, t, J = 7.0 Hz, H-7), 1.56 (6H, s, (CH3)2-10),
1.36 (6H, s, (CH3)2-8), 0.67 (3H, t, J = 7.5 Hz, H-30); 13C NMR (CDCl3,
75 MHz) d: 162.4, 157.7, 153.1, 149.2, 139.9, 114.8, 109.2, 103.8,
102.7, 75.1, 40.2, 35.1, 31.2, 30.8 (2ꢀ), 26.4 (2ꢀ), 17.2, 10.1; EIMS m/
z (rel. int.%): 344 (M+, 20), 315 (68), 259 (100); HR-EIMS m/z
316.1575 (calcd for C19H24O4: 316.1675); Anal. (C19H24O4) C, H.
4.4.1. 10-(1,1-Dimethylallyl)-5-methoxy-8,8-dimethyl-7,8-
dihydropyrano[3,2-c]chromen-2,6-dione (7)
247 mg (72.3%), mp 195–196 °C; 1H NMR (CDCl3, 300 MHz) d:
7.97 (1H, d, J = 9.8 Hz, H-4), 6.23 (1H, dd, J = 16.8, 10.1 Hz, H-20),
6.22 (1H, d, J = 9.8 Hz, H-3), 4.92 (1H, d, J = 16.8 Hz, Hb-30), 4.87
(1H, d, J = 10.1 Hz, Ha-30), 3.91 (3H, s, OCH3-5), 2.62 (2H, s, H-7),
1.66 (6H, s, (CH3)2-10), 1.46 (6H, s, (CH3)2-8); 13C NMR (CDCl3,
75 MHz) d: 190.3, 162.0, 159.7, 157.5, 157.1, 149.6, 139.2, 119.5,
112.5, 111.6, 108.5, 108.2, 79.9, 63.5, 49.9, 41.3, 28.8 (2ꢀ), 26.2
(2ꢀ); EIMS m/z (rel. int.%): 342 (M+, 50), 327 (22), 271 (100); HR-
EIMS m/z 342.1465 (calcd for C20H22O5: 342.1467); Anal.
(C20H22O5) C, H.
4.3.4. 10-(1,1-Dimethylpropyl)-5-methoxy-8,8-dimethyl-7,8-
dihydro-6H-pyrano[3,2-c]chromen-2-one (12)
91.3 mg (90.7%), mp 91–92 °C; 1H NMR (CDCl3, 300 MHz) d:
7.86 (1H, d, J = 9.6 Hz, H-4), 6.15 (1H, d, J = 9.6 Hz, H-3), 3.80 (3H,
s, OCH3-5), 2.79 (2H, t, J = 6.9 Hz, H-6), 1.92 (2H, q, J = 7.4 Hz, H-
20), 1.77 (2H, t, J = 6.9 Hz, H-7), 1.58 (6H, s, (CH3)2-10), 1.37 (6H, s,
(CH3)2-8), 0.68 (3H, t, J = 7.4 Hz, H-30); 13C NMR (CDCl3, 75 MHz)
d: 161.2, 157.8, 153.2, 153.1, 139.2, 118.5, 111.4, 111.0, 106.5,
75.5, 61.8, 40.4, 35.0, 31.4, 30.6 (2ꢀ), 26.7 (2ꢀ), 17.4, 10.1; EIMS
m/z (rel. int.%): 330 (M+, 48), 301 (100), 245 (99); HR-EIMS m/z
330.1832 (calcd for C20H26O4: 330.1831); Anal. (C20H26O4) C, H.
4.4.2. 10-(1,1-Dimethylallyl)-5-methoxy-8,8-dimethyl-8H-
pyrano[3,2-c]chromen-2-one (11)
296.0 mg (90.2%), mp 86–87 °C; 1H NMR (CDCl3, 300 MHz) d:
7.86 (1H, d, J = 9.5 Hz, H-4), 6.56 (1H, d, J = 10.0 Hz, H-6), 6.30
(1H, dd, J = 17.3, 10.6 Hz, H-20), 6.18 (1H, d, J = 9.5 Hz, H-3), 5.69
(1H, d, J = 10.0 Hz, H-7), 4.93 (1H, d, J = 17.3 Hz, Hb-30), 4.87 (1H,
d, J = 10.6 Hz, Ha-30), 3.82 (3H, s, OCH3-5), 1.66 (6H, s, (CH3)2-10),
1.44 (6H, s, (CH3)2-8); 13C NMR (CDCl3, 75 MHz) d: 160.6, 155.9,
153.8, 151.1, 149.7, 138.8, 130.2, 119.0, 116.1, 111.5, 108.0,
107.4, 77.3, 63.3, 41.0, 29.3 (2ꢀ), 27.4 (2ꢀ); EIMS m/z (rel. int.%):
326 (M+, 100), 165 (54), 151 (89); HR-EIMS m/z 326.1517 (calcd
for C20H22O4: 326.1518); Anal. (C20H26O4) C, H.
4.3.5. 3,10-Bis-(1,1-dimethylpropyl)-5-hydroxy-8,8-dimethyl-
7,8-dihydro-6H-pyrano[3,2-c]chromen-2-one (15)
82.9 mg (82.6%), mp 237–238 °C; 1H NMR (CDCl3, 300 MHz) d:
7.83 (1H, s, H-4), 5.52 (1H, br s, D2O-exchangeble, OH-5), 2.66 (2H,
t, J = 7.0 Hz, H-6), 1.89 (2H, q, J = 7.5 Hz, H-20), 1.86 (2H, q,
J = 7.7 Hz, H-200), 1.83 (2H, t, J = 7.0 Hz, H-7), 1.63 (6H, s, (CH3)2-10),
1.35 (6H, s, (CH3)2-8), 1.31 (6H, s, (CH3)2-100), 0.71 (2H, t, J = 7.7 Hz,
H-300), 0.68 (2H, t, J = 7.5 Hz, H-30); 13C NMR (CDCl3, 75 MHz) d:
160.6, 156.1, 152.4, 148.4, 133.9, 128.5, 114.2, 102.9, 102.8, 74.6,
40.1, 38.5, 35.1, 32.2, 31.4, 30.7 (2ꢀ), 26.8 (2ꢀ), 26.4 (2ꢀ), 17.3,
10.1, 9.4; EIMS m/z (rel. int.%): 386 (M+, 8), 371 (78), 357 (38); HR-
EIMS m/z 386.2460 (calcd for C24H34O4: 386.2457); Anal.
(C24H34O4) C, H.
4.4.3. 3,10-Bis-(1,1-dimethylallyl)-5-methoxy-8,8-dimethyl-8H-
pyrano[3,2-c]chromen-2-one (16)
379.9 mg (96.3%), mp 142–143 °C; 1H NMR (CDCl3, 300 MHz) d:
7.73 (1H, s, H-4), 6.57 (1H, d, J = 9.9 Hz, H-6), 6.30 (1H, dd, J = 17.4,
10.4 Hz, H-20), 6.18 (1H, dd, J = 17.6, 10.5 Hz, H-200), 5.67 (1H, d,
J = 9.9 Hz, H-7), 5.09 (1H, d, J = 17.6 Hz, H-3b00), 5.08 (1H, d,
J = 10.5 Hz, H-3a00), 4.95 (1H, d, J = 17.4 Hz, H-3b0), 4.87 (1H, d,
J = 10.4 Hz, H-3a0), 3.82 (3H, s, OCH3-5), 1.65 (6H, s, (CH3)2-10),
1.47 (6H, s, (CH3)2-100), 1.44 (6H, s, (CH3)2-8); 13C NMR (CDCl3,
75 MHz) d: 159.4, 154.9, 153.1, 151.0, 149.8, 145.5, 132.8, 130.3,
130.1, 118.4, 116.5, 111.9, 111.5, 108.0, 107.7, 77.2, 63.2, 41.0,
40.2, 29.2 (2ꢀ), 27.4 (2ꢀ), 26.0 (2ꢀ); EIMS m/z (rel. int.%): 394
(M+, 96), 380(100); HR-EIMS m/z 394.2141 (calcd for C25H30O4:
394.2144); Anal. (C25H30O4) C, H.
4.3.6. 3,10-Bis-(1,1-dimethylpropyl)-5-methoxy-8,8-dimethyl-
7,8-dihydro-6H-pyrano[3,2-c]chromen-2-one (17)
88.4 mg (88.3%), mp 102–103 °C; 1H NMR (CDCl3, 300 MHz) d:
7.66 (1H, s, H-4), 3.82 (3H, s, OCH3-5), 2.80 (2H, t, J = 6.8 Hz, H-
6), 1.93 (2H, q, J = 7.4 Hz, H-20), 1.85 (2H, q, J = 7.4 Hz, H-200), 1.77
(2H, t, J = 6.8 Hz, H-7), 1.59 (6H, s, (CH3)2-10), 1.36 (6H, s, (CH3)2-
8), 1.32 (6H, s, (CH3)2-100), 0.71 (2H, t, J = 7.4 Hz, H-300), 0.69 (2H,
t, J = 7.4 Hz, H-30); 13C NMR (CDCl3, 75 MHz) d: 160.0, 156.5,
152.7, 152.3, 133.6, 129.8, 117.7, 110.6, 106.9, 75.1, 61.5, 40.3,
40.0, 35.1, 32.1, 31.6, 30.6 (2ꢀ), 26.7 (4ꢀ), 17.4, 10.1, 9.3; EIMS
m/z (rel. int.%): 400 (M+, 37), 371 (100), 315(100); HR-EIMS m/z
400.2617 (calcd for C25H36O4: 400.2614); Anal. (C25H36O4) C, H.
4.5. General procedure for compounds 6 and 9
To a solution of corresponding coumarin (0.3 mmol) in CH2Cl2
(10 mL) was added mCPBA (88.8 mg, 0.36 mmol). The mixture
was then stirred for 24 h under an argon atmosphere and the sol-
vent was removed to afford a residue, which was purified by col-
umn chromatography on aluminum oxide gel.
4.3.7. 5-Methoxy-8,8-dimethyl-7,8-dihydro-6H-pyrano[3,2-
c
]chromen-2-one (20)
94.3 mg (94.4%), mp 142–145 °C; 1H NMR (CDCl3, 300 MHz) d:
7.84 (1H, d, J = 9.6 Hz, H-4), 6.54 (1H, s, H-10), 6.17 (1H, d,
J = 9.6 Hz, H-3), 3.85 (3H, s, OCH3-5), 2.77 (2H, t, J = 6.7 Hz, H-6),
1.81 (2H, t, J = 6.7 Hz, H-7), 1.36 (6H, s, (CH3)2-8); 13C NMR (CDCl3,
75 MHz) d: 161.4, 158.5, 155.3, 154.2, 138.6, 112.0, 111.6, 106.6,
4.5.1. 5-Hydroxy-8,8-dimethyl-10-(1-methyl-1-oxiranylethyl)-
7,8-dihydropyrano[3,2-c]chromen-2,6-dione (6)
81.0 mg (78.5%), mp 150–151 °C; 1H NMR (CDCl3, 300 MHz) d:
13.10 (1H, br s, D2O-exchangeable, OH-5), 8.04 (1H, d, J = 9.6 Hz,