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H.-W. Chu et al. / Tetrahedron 60 (2004) 2647–2655
0.8 mmol) for 2 h to provide the desired 5,8-dihydroxy-7-
methoxy-2-(4-methoxyphenyl)-4-benzopyrone (141 mg,
residue was subjected to column chromatography (SiO2,
CH2Cl2/ether 4:1) to provide the corresponding 3-hydroxy-
5,7-dimethoxy-2-(3,4-dimethoxyphenyl)-4-benzopyrone (10)
(0.36 g, 86%) as a yellow solid: mp 184–186 8C (CH2Cl2)
(lit.26 mp 197–198 8C); 1H NMR (200 MHz, CDCl3) d 3.89,
3.92, 3.97, and 4.03 (3H each, s, OMex4), 6.33 and 6.53 (1H
each, d, J¼2.1 Hz, 6,8-H), 6.98 (1H, d, J¼9.1 Hz, 5-H),
6.95 (1H, d, J¼9.1 Hz, 6-H), 7.81 (1H, s, 2-H); 13C NMR
(50 MHz, CDCl3) d 56.5, 56.6, 56.7, 57.5, 93.1, 96.3, 106.8,
111.0, 111.5, 121.3, 124.4, 138.2, 142.8, 149.5, 150.9,
159.5, 161.2, 165.0, 172.5.
89%) as a solid: mp 269–271 8C (acetone) (lit.21 mp
214–215 8C); 1H NMR (200 MHz, DMSO) d 3.96 and 4.00
(3H each, s, OMex2), 6.65 (1H, s, 6-H), 6.98 (1H, s, 3-H),
7.23 and 8.22 (2H each, d, J¼8.8 Hz, 2,6-H, 3,5-H), 9.01
(1H, s, OH); HRMS (EI) calcd for C17H14O6: 314.0790 [M],
found: 314.0783 [M]þ. To a mixture of dihydroxyflavone
(180 mg, 0.57 mmol) and K2CO3 (1.5 equiv. 120 mg) in
acetone (10 mL) was added Me2SO4 (54 mL, 0.57 mmol)
dropwise at room temperature, and then refluxed for 3 h.
The resulting solution was cooled and was added H2O
(2 mL), and extracted with CH2Cl2 (3£20 mL). The
organic layer was concentrated in vacuo, and the residue
was subjected to column chromatography (SiO2, CH2Cl2)
to afford the desired product 27 (180 mg, 96%) as a white
A sealed tube of 10 (0.30 g, 0.84 mmol) and BBr3 (5 equiv.
1 M, 4.2 mL) in CH2Cl2 (10 mL) was refluxed for 6 h, and
then cooled to room temperature. The brown mixture was
dissolved in MeOH and subjected to column chromato-
graphy (SiO2, EtOAc/CH2Cl2 1:4) to obtain 7 (0.21 g, 83%)
as a yellow solid: mp 320 8C (acetone) (lit.25b mp 318–
1
solid: mp 220.5 8C (CH2Cl2) (lit.22 mp 220–221 8C); H
NMR (200 MHz, CDCl3) d 3.90, 3.94, and 3.95 (3H each,
s, OMex3), 6.43 (1H, s, 6-H), 6.59 (1H, s, 3-H), 7.03 and
7.91 (2H each, d, J¼8.8 Hz, 2,6-H, 3,5-H); 13C NMR
(50 MHz, CDCl3) d 55.5, 56.3, 61.6, 95.7, 103.8, 104.8,
114.5, 123.5, 128.1, 128.9, 149.4, 157.5, 158.4, 162.7,
163.9, 182.6.
1
320 8C); H NMR (300 MHz, (CD3)2COþDMSO) d 6.22
and 7.78 (1H each, d, J¼2.1 Hz, 6,8-H), 6.46 (1H, d,
J¼1.8 Hz, 20-H), 6.95 (1H, d, J¼8.4 Hz, 50-H), 7.64 (1H, dd,
J¼8.4, 2.1 Hz, 60-H); 13C NMR (75.47 MHz, (CD3)2-
COþDMSO) d 92.6, 97.4, 102.2, 114.0, 114.4, 119.5,
121.8, 134.9, 144.2, 145.3, 146.7, 155.9, 160.4, 163.5,
174.8.
3.1.9. 5,7,8-Trimethoxy-2-(3,4-dimethoxyphenyl)-4-ben-
zopyrone (28) and isosinensetin (1). A solution of 26a
(100 mg, 0.30 mmol) in CH2Cl2 was treated with DMD
(15 mL, 0.30 mmol) for 20 min to give the regioselective
product 5,8-dihydroxy-7-methoxy-2-(3,4-dimethoxyphe-
nyl)-4-benzopyrone (98 mg, 93%) as a yellow solid: mp
3.1.11. 3,5,7-Trimethoxy-2-(3,4-dimethoxyphenyl)-4-
benzopyrone (9). To a mixture of 10 (1.0 g, 2.8 mmol)
and K2CO3 (1.2 equiv. 0.46 g) in acetone (80 mL) was
added Me2SO4 (0.32 mL, 3.3 mmol) dropwise at room
temperature, and then refluxed for 1 h. The resulting
solution was cooled and was added H2O (10 mL), and
extracted with CH2Cl2 (3£200 mL). The organic layer was
concentrated in vacuo, and the residue was subjected to
column chromatography (SiO2, CH2Cl2/ether 4:1) to give
the desired pentamethoxylflavone 9 (1.0 g, 96%) as a white
solid: mp 154–155 8C (acetone) (lit.27 mp 153–154 8C).
1
254–256 8C (acetone) (lit.23a mp 250–251 8C); H NMR
(200 MHz, CDCl3) d 3.97 and 3.99 (3H each, s, OMex3),
6.44 (1H, s, 6-H), 6.58 (1H, s, 3-H), 6.99 and 7.65 (1H each,
d, J¼8.4 Hz, 5,6-H), 7.51 (1H, s, 2-H). To a mixture of
dihydroxyflavone (90 mg, 0.26 mmol) and K2CO3
(1.5 equiv. 54 mg) in acetone (5.0 mL) was added
Me2SO4 (30 mL, 0.32 mmol) dropwise at room temperature,
and then refluxed for 1 h. The resulting solution was cooled
and was added H2O (1 mL), and extracted with CH2Cl2
(3£10 mL). The organic layer was concentrated in vacuo,
and the residue was subjected to column chromatography
(SiO2, CH2Cl2/ether 2:1) to afford the desired products 1
(55 mg, 59%) as a yellow solid and 28 (40 mg, 41%) as a
white solid. 28: mp 190–192 8C (acetone) (lit.23b mp 199–
200 8C); HRMS (EI) calcd for C20H20O7: 372.1209 [M],
found: m/z 372.1216 [M]þ; 1: mp 199–201 8C (CH2Cl2)
(lit.24 mp 207–208 8C); HRMS (EI) calcd for C19H18O7:
358.1053 [M], found: 358.1051 [M]þ.
3.1.12. 5-Hydroxy-3,7-dimethoxy-2-(3,4-dimethoxyphe-
nyl)-4-benzopyrone (11).
A solution of 9 (1.0 g,
2.7 mmol) in CH2Cl2 (20 mL) was cooled to 0 8C for
30 min, and added BBr3 (1 equiv. 1 M 2.7 mL) into the
solution dropwise. The brown mixture was stirred at 0 8C for
30 min, and then MeOH was introduced for quenching the
reaction. The solvent was removed in vacuo, and the residue
was subjected to column chromatography (SiO2, CH2Cl2/
ether 4:1) to afford the corresponding 11 (0.95 g, 99%) as a
yellow solid: mp 158–159 8C (CH2Cl2) (lit.28 mp 160–
1
161 8C); H NMR (200 MHz, CDCl3) d 3.85 and 3.96 (3H
3.1.10. Quercetin (7). To a suspension of 26a (1.5 g,
4.6 mmol) and K2CO3 (1.5 equiv. 0.95 g) in acetone
(50 mL) was added Me2SO4 (0.65 mL, 6.9 mmol) dropwise
at room temperature, and then refluxed for 2 h. The resulting
solution was cooled and was added H2O (10 mL), and
extracted with CH2Cl2 (3£200 mL). The organic layer was
concentrated in vacuo, and the residue was subjected to
column chromatography (SiO2, CH2Cl2/ether 2:1) to give
the desired tetramethoxylflavone 26b (1.5 g, 97%) as a
white solid: mp 190–192 8C (CH2Cl2) (lit.25a mp 188–
190 8C). The amount of DMD (50 mL) was added rapidly
under N2 to a cooled solution of methylated flavone 26b
(0.40 g, 1.2 mmol) in dried CH2Cl2 (50 mL). Stirring was
continued for 30 min. The solvent was removed and the
each, s, OMex4), 6.30 and 6.40 (1H each, d, J¼2.1 Hz, 6,8-
H), 6.96 (1H, d, J¼8.5 Hz, 5-H), 7.66 (1H, s, 2-H), 7.72
(1H, d, J¼8.5 Hz, 6-H); 13C NMR (50 MHz, CDCl3) 56.4,
56.6, 56.6, 60.7, 92.7, 98.4, 106.6, 111.4, 111.8, 122.7,
123.5, 139.5, 149.3, 152.0, 156.3, 157.2, 162.5, 166.0, 179.3.
3.1.13. 5,8-Dihydroxy-3,7-dimethoxy-2-(3,4-dimethoxy-
phenyl)-4-benzopyrone (29). The 11 (0.30 g, 0.84 mmol)
in CH2Cl2 was added with DMD (25 mL, 1.0 mmol) for
50 min to obtain the regioselective product 29 (0.28 g, 89%)
as a yellow solid: mp 238–240 8C (acetone) (lit.29 mp 240–
242 8C); 1H NMR (200 MHz, CDCl3) d 3.87, 3.88, 3.97, and
3.98 (3H ea0ch, s, OMex4), 6.44 (1H, s, 6-H), 7.00 (1H, d,
J¼8.5 Hz, 5 -H), 7.79 (1H, d, J¼1.9 Hz, 20-H), 7.80 (1H, dd,