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T. Oshitari et al. / Bioorg. Med. Chem. 19 (2011) 7085–7092
m), 6.84 (1H of the keto form, m), 6.77 (1H of the enol form, m), 5.08
(4H of the enol form and 4H of the keto form, br s, PhCH2O), 4.56 (2H
of the keto form, ArCO-CH2-COAr), 4.10 (3H of the enol form and 3H
of the keto form, s, OCH3), 3.90 (3H of the enol form, s, OCH3), 3.880
(3H of the keto form, s, OCH3), 3.877 (3H of the enol form, s, OCH3),
3.86 (3H of the enol form, s, OCH3), 3.74 (3H of the keto form, s,
OCH3), 3.69 (3H of the keto form, s, OCH3); HRMS calcd. for [MꢁH]ꢁ
of C33H32O9: 571.1974, found: 571.1967.
tate. The combined organic layers were concentrated. The residual
yellow solids were purified on a silica gel column (hexane/ethyl
acetate = 2/1) to give 5a (22.2 mg, 61.9 lmol, 86% yield) as white
crystals: mp 223 °C; IR (KBr) 3442, 2935, 1624, 1574, 1450 cmꢁ1
;
1H NMR (CDCl3) d: 7.99 (1H, dd, J = 1.6, 8.0 Hz), 7.86 (1H, br s),
7.41 (1H, ddd, J = 1.6, 8.0, 8.0 Hz), 7.30 (1H, br d, J = 8.0 Hz), 7.02
(1H, ddd, J = 1.6, 8.0, 8.0 Hz), 4.14 (3H, s), 4.05 (3H, s), 4.02 (3H,
s), 3.99 (3H, s); 13C NMR (CDCl3) d: 179.9, 160.8, 157.6, 151.8,
148.2, 147.8, 144.3, 138.0, 132.9, 127.9, 119.8, 118.3, 116.8,
114.1, 110.3, 62.4, 62.1, 61.9, 61.7; HRMS calcd. for [M+H]+ of
5.1.1.9. 20-Benzyloxy-5,6,7,8-tetramethoxyflavone (11a).
A
mixture of 10a (248 mg, 0.532 mmol) and p-TsOH (monohydrate,
25 mg, 0.13 mmol) in benzene (5 mL) was heated at reflux for 7 h
with azeotropic removal of water using Dean-Stark trap. After being
cooled to rt, the mixture was diluted with ethyl acetate (30 mL) and
washed with sat. aq. NaHCO3 (2 ꢂ 20 mL). The organic layer was
dried (MgSO4) and concentrated. The residue was chromato-
graphed (silica gel, toluene/ethyl acetate = 1/0–5/1–2/1) to afford
11a (224 mg, 0.499 mmol, 94% yield) as yellow crystals: mp 99–
C19H18O7: 359.1125, found: 359.1120.
5.1.1.14. 30-Hydroxy-5,6,7,8-tetramethoxyflavone (5b).
According to a similar procedure as described for the prepara-
tion of 5a, 5b was obtained in 84% as white crystals. mp 177 °C;
IR (KBr) 3314, 2941, 1644, 1605 cmꢁ1 1H NMR (CDCl3) d: 7.66
;
(1H, br t, J = 1.8 Hz), 7.51 (1H, br d, J = 8.4 Hz), 7.38 (1H, dd,
J = 8.4, 8.4 Hz), 7.10 (1H, dd, J = 1.8, 8.4 Hz), 6.84 (1H s), 4.12 (3H,
s), 4.03 (3H, s), 3.99 (3H, s), 3.96 (3H, s); 13C NMR (CDCl3)
d:178.1, 162.1, 157.4, 151.9, 148.4, 147.9, 144.3, 138.1, 132.4,
130.3, 119.4, 117.8, 114.7, 113.2, 107.8, 62.25, 62.16, 61.8, 61.7;
HRMS calcd. for [M+H]+ of C19H18O7: 359.1125, found: 359.1123.
101 °C; IR (KBr) 2941, 1640, 1447, 1359 cmꢁ1 1H NMR (CDCl3) d:
;
7.90 (1H, dd, J = 2.0, 8.0 Hz), 7.43–7.30 (6H, m), 7.13–7.04 (2H, m),
7.01 (1H s) 5.25 (2H s), 4.09 (3H, s), 3.96 (3H, s), 3.95 (3H, s), 3.94
(3H, s); 13C NMR (CDCl3) d:177.5, 158.9, 156.8, 151.2, 148.1,
147.9, 143.8, 138.0, 136.1, 132.0, 129.3, 128.6 (2C), 128.0, 126.9
(2C), 121.2, 121.0, 114.8, 113.3 (2C), 70.6, 62.2, 62.0, 61.8, 61.6;
HRMS calcd. for [M+H]+ of C26H24O7: 449.1595, found: 449.1596.
5.1.1.15. 40-Hydroxy-5,6,7,8-tetramethoxyflavone (5c).
According to a similar procedure as described for the prepara-
tion of 5a, 5c was obtained in 97% yield as white crystals: mp
199–201 °C (Lit.18,19 197–199 °C); IR (KBr) 3480, 2941, 1622,
5.1.1.10. 30-Benzyloxy-5,6,7,8-tetramethoxyflavone (11b).
According to a similar procedure as described for the prepara-
tion of 11a, 11b was obtained in 95% yield as yellow crystals: mp
102–104 °C; IR (KBr) 2937, 1634, 1590, 1464 cmꢁ1; 1H NMR (CDCl3)
d: 7.54–7.51 (2H, m), 7.48–7.35 (6H, m), 7.14 (1H, m), 6.67 (1H, s),
5.16 (2H s), 4.11 (3H, s), 4.00 (3H, s), 3.95 (6H, s); 13C NMR (CDCl3) d:
177.3, 160.9, 159.2, 151.5, 148.3, 147.8, 144.2, 138.1, 136.4, 132.9,
130.2, 128.7 (2C), 128.2, 127.4 (2C), 118.7, 118.1, 114.9, 112.3,
108.2, 70.2, 62.23, 62.22, 62.0, 61.8; HRMS calcd. for [M+H]+ of
1583, 1558 cmꢁ1 1H NMR (CDCl3) d: 7.82 (2H, br d, J = 8.8 Hz),
;
7.07 (2H, br d, J = 8.8 Hz), 6.63 (1H s), 4.12 (3H, s), 4.03 (3H, s),
3.97 (3H, s), 3.96 (3H, s); 13C NMR (CDCl3) d: 178.0, 162.2, 160.2,
151.6, 148.2, 147.7, 144.1, 138.0, 128.0 (2C), 122.6, 116.3 (2C),
114.4 105.9, 62.3, 62.1, 61.8, 61.7; HRMS calcd. for [M+H]+ of
C19H18O7: 359.1125, found: 359.1120.
5.1.1.16. 30,50-Dihydroxy-5,6,7,8-tetramethoxyflavone (5d).
According to a similar procedure as described for the prepara-
tion of 5a, 5d was obtained in 89% yield as white crystals: mp
C26H24O7: 449.1595, found: 449.1592.
5.1.1.11. 40-Benzyloxy-5,6,7,8-tetramethoxyflavone (11c).
According to a similar procedure as described for the prepara-
tion of 11a, 11c was obtained in 70% yield as yellow crystals: mp
142–144 °C (Lit.18 136–139 °C); IR (KBr) 2941, 1638, 1605,
246–248 °C; IR (KBr) 3326, 3188, 2941, 1636, 1595 cmꢁ1 1H
;
NMR (DMSO-d6) d: 9.72, (2H, s), 6.84 (2H, d, J = 1.8 Hz), 6.57 (1H,
s), 6.42 (1H, dd, J = 1.8, 1.8 Hz), 4.01 (3H, s), 3.95 (3H, s), 3.83
(3H, s), 3.76 (3H, s); 13C NMR (DMSO-d6) d: 175.8, 160.6, 159.0
(2C), 151.0, 147.5, 147.2, 143.6, 137.7, 132.6, 114.3, 107.2, 105.7,
104.0 (2C), 61.94, 61.88, 61.5, 61.4; HRMS calcd. for [M+H]+ of
1514 cmꢁ1 1H NMR (CDCl3) d: 7.87 (2H, br d, J = 8.8 Hz), 7.46–
;
7.34 (5H, m), 7.09 (2H, br d, J = 8.8 Hz), 6.61 (1H s), 5.15 (2H s),
4.10 (3H, s), 4.02 (3H, s), 3.95 (6H, s); 13C NMR (CDCl3) d: 177.1,
161.3, 161.0, 151.2, 148.2, 147.6, 143.9, 137.9, 136.1, 128.6 (2C),
128.1, 127.6 (2C), 127.3 (2C), 123.9, 115.3 (2C), 114.8, 106.6,
70.1, 62.2, 62.0, 61.8, 61.6; HRMS calcd. for [M+H]+ of C26H24O7:
449.1595, found: 449.1593.
C19H18O8: 375.1074, found: 375.1078.
5.1.1.17. 20,5,6,7,8-Pentamethoxyflavone (6a). To a mixture of
5a (28.4 mg, 79.3 mol) and K2CO3 (33 mg, 0.24 mmol) in DMF
l
(2 mL) was added iodomethane (0.03 mL, 0.4 mmol). The reaction
mixture was stirred at rt for 5 h, and then partitioned between
water (20 mL) and toluene (20 mL). The organic layer separated
was washed with brine, and dried (MgSO4). Filtration followed by
concentration gave yellowish solids (29 mg), which were purified
on a silica gel column (hexane/ethyl acetate = 2/1–1/1) to afford
6a (23.5 mg, 63.1 mmol, 80% yield) as white crystals: mp 82–
5.1.1.12. 30,50-Dibenzyloxy-5,6,7,8-tetramethoxyflavone (11d).
According to a similar procedure as described for the prepara-
tion of 11a, 11d was obtained in 90% yield as white crystals: mp
88–90 °C; IR (KBr) 2937, 1641, 1595 cmꢁ1 1H NMR (CDCl3) d:
;
7.46–7.33 (10H, m), 7.14 (2H, br d, J = 2.0 Hz), 6.77 (1H, dd,
J = 2.0, 2.0 Hz), 6.64 (1H s), 5.12 (4H s), 4.10 (3H, s), 3.97 (3H, s),
3.95 (6H, s); 13C NMR (CDCl3) d: 177.3, 160.8, 160.3 (2C), 151.5,
148.3, 147.8, 144.2, 138.1, 136.3 (2C), 133.5, 128.7 (4C), 128.2
(2C), 127.5 (4C), 114.9, 108.4, 105.3 (3C), 70.3 (2C), 62.3, 62.0,
61.8, 61.7; HRMS calcd. for [M+H]+ of C33H30O8: 555.2013, found:
555.2013.
84 °C; IR (KBr) 2941, 1634, 1458, 1445 cmꢁ1 1H NMR (CDCl3) d:
;
7.94 (1H, dd, J = 1.6, 7.6 Hz), 7.48 (1H, ddd, J = 1.6, 7.6, 7.6 Hz),
7.12 (1H, ddd, J = 1.6, 7.6, 7.6 Hz), 7.06–7.03 (2H, m), 4.10 (3H, s),
3.99 (3H, s), 3.96 (6H, s), 3.94 (3H, s); 13C NMR (CDCl3) d:177.8,
158.7, 158.0, 151.3, 148.3, 148.0, 143.9, 138.1, 132.3, 129.1, 120.9,
120.6, 114.8, 113.2, 111.7, 62.3, 62.0, 61.9, 61.7, 55.6; HRMS calcd.
for [M+H]+ of C20H20O7: 373.1282, found: 373.1293.
5.1.1.13. 20-Hydroxy-5,6,7,8-tetramethoxyflavone (5a). A mix-
ture of 11a (32.4 mg, 72.2
l
mol) and 20% Pd(OH)2 on carbon
5.1.1.18. 30,5,6,7,8-Pentamethoxyflavone (6b). According to a
similar procedure as described for the preparation of 6a, 6b was ob-
tained in 90% as white crystals: mp 100 °C; IR (KBr) 2940, 1651,
(6 mg) in ethyl acetate (1.5 mL) and ethanol (1.5 mL) was stirred
at rt for 2 h under a hydrogen atmosphere. The mixture was passed
through a pad of Celite and the cake was washed with ethyl ace-
1593, 1467 cmꢁ1 1H NMR (CDCl3) d: 7.52 (1H, ddd, J = 0.9, 1.8,
;