Med Chem Res
ether / EtOAc, v/v, 5:1) to afford 3 (yield: 62%) as yellow
solid, m.p. 182–184 °C; H NMR (400 MHz, CDCl3): δ
(s, 6H, –OCH3); 13C NMR (CDCl3): δ 177.3, 161.1, 151.9,
151.5, 149.2, 148.4, 147.7, 144.1, 123.9, 119.9, 114.7,
111.2, 108.5, 106.7, 62.3, 62.0, 61.8, 61.7, 56.1, 55.9; MS
(m/z, EI): 402 (M+), 387 (100), 371, 344, 326, 298, 283,
239, 225, 198, 197, 182, 162, 153, 139, 91, 83, 77; HRMS
(EI): m/z [M]+ calcd for C21H22O8: 402.1315, found:
402.1314.
1
7.60 (d, J = 8.9 Hz, 2H, H-2′, and H-6′), 6.93 (d, J = 8.9
Hz, 2H, H-3′, and H-5′), 6.53 (s, 1H, H-3), 4.01, 3.92, 3.85,
3.82 (each, s, each 3H, –OCH3); 13C NMR (100 MHz,
CDCl3): δ 178.8, 162.5, 159.6, 147.3, 146.7, 143.0, 142.3,
137.1, 136.5, 128.7, 122.8, 114.9, 105.7, 103.6, 61.3, 61.0,
60.2, 55.2; EIMS: m/z 358 [M]+.
Synthesis of 3-O-prenyl-5,6,7,8,4′-pentamethoxyflavonol
(15)
Synthesis of 7-hydroxy-5,6,8,3′, 4′-pentamethoxyflavone
(4)
To a mixture of compound 7 (100 mg, 0.26 mmol) and
According to a similar procedure as described for the pre-
paration of 3. 4 was obtained (yield: 76%) as yellow soild,
m.p. 115–117 °C; 1H NMR (400 MHz, CDCl3): δ 7.58 (d, J
= 8.3 Hz, 1H, H-6′), 7.46 (d, J = 7.6 Hz, 1H, H-2′), 7.06 (d.
J = 7.3 Hz, 1H, H-5′), 6.68 (s, 1H, H-3), 4.12, 4.03, 3.83
(each, s, each 3H, –OCH3), 3.96 (s, 6H, –OCH3); 13C NMR
(100 MHz, CDCl3): δ 177.8, 162.6, 158.6, 149.3, 147.6,
146.5, 143.0, 137.3, 136.7, 123.6, 119.6, 116.5, 112.6,
105.9, 103.3, 61.0, 60.3, 60.0, 56.2; EIMS: m/z 388 [M]+.
anhydrous K2CO3 (110 mg, 0.8 mmol) in dry acetone
(20 mL),
a
solution of prenyl bromide (0.06 mL,
0.26 mmol) in acetone (3 mL) was added dropwise upon
stirring for 3 h, then the reaction mixture was filtered and
evaporated. The residue was subjected to chromatography
on silica gel with petroleum ether-ethyl acetate (v/v,5:1) as
eluent to give 114 mg of compound 15 as a yellow soild
(yield: 95%), m.p. 123–125 °C; 1H NMR (400 MHz,
CDCl3): δ 8.19 (d, J = 8.8 Hz, 2H, H-2′ and 6′), 7.03 (d,
J = 8.8 Hz, 2H, H-3′ and 5′), 5.47 (s, 1H, CH), 4.57 (s, 2H,
CH2), 4.11, 4.01, 3.98, 3.96, 3.91 (each, s, each 3H,
-OCH3), 1.71 (s, 3H, CH3), 1.66 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3): δ 173.0, 160.2, 152.8, 150.1, 147.1,
145.8, 142.7, 138.3, 137.92, 136.8, 129.2. 122.6, 119.1,
114.0, 112.8, 98.9, 67.6, 61.3, 61.0, 60.8, 60.6, 54.4, 24.8,
17.1; IR (KBr) v 3417.03, 3234.66, 2029.75, 1635.74,
1509.74, 1453.52, 1360.70, 1257.00, 1171.23, 1050.70,
Synthesis of 5,6,7,8,4′-pentamethoxyflavone (tangeretin)
(5)
Me2SO4 (0.1 mL, 3 equiv.) was added dropwise to stirred
solution of 3 (135 mg) in acetone and K2CO3 (0.91 g, 6.48
mmol) at 65 °C. The reaction was terminated after 5 h, and
the mixture was filtered. The solution was evaporated to
afford a solid residue. The crude solid was chromato-
graphed on silica gel using petroleum ether/ethyl acetate (v/
v, 3:1) as eluent to afford light yellow crystals of 5 (115 mg,
yield: 86%), m.p. 151–153 °C (lit[12]. 152–153 °C); 1H
NMR (CDCl3): δ 7.80 (d, J = 8.8 Hz, 2H, H-2′ and 6′), 6.94
(d, J = 8.8 Hz, 2H, H-3′ and 5′), 6.52 (s, 1H, H-3), 4.03,
3.94, 3.87, 3.81, (each, s, each 3H, –OCH3); 13C NMR
(CDCl3): δ 176.3, 161.3, 160.1, 150.3, 147.3, 146.7, 143.0,
137.1, 126.7, 122.8, 113.8, 113.5, 105.6, 61.2, 61.0, 60.8,
60.6, 54.5; IR (KBr): ν 2946, 2843, 1650, 1607, 1587,
1512, 1462, 1363, 1265, 1181, 1074, 968, 830 cm–1; MS
(m/z, EI): 372 (M+), 327, 315, 287, 259, 194, 135, 77, 57;
HRMS (EI): m/z [M]+ calcd for C20H20O7: 372.1209,
found: 372.1204.
977.21, 801.96, 753.41, 621.55, 481.87 cm−1
.
Synthesis of 3-O-prenyl-5,6,7,8,3′,4′-hexamethoxyflavonol
(16)
Compound 16 was prepared from compound 8 and prenyl
bromide as described for the preparation of compound 15
from compound 7. Yellow solid, (yield: 94%), m.p.
1
140–143 °C; H NMR (400 MHz, CDCl3): δ 7.83 (d, J =
2.0 Hz, 1H, H-6′), 7.77 (dd, J = 8.6, 2.1 Hz, 1H, H-5′), 6.92
(d, J = 8.6 Hz, 1H, H-2′), 5.42 (t, J = 7.3 Hz, 1H, CH), 4.52
(d, J = 7.3 Hz, 2H, CH2), 4.02, 3.93, 3.90, 3.88, 3.87 (s,
each, s, each 3H, –OCH3), 1.63 (s, 3H, CH3), 1.56 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3): δ 173.0, 152.4, 150.2,
149.8, 147.5, 147.2, 145.7, 142.7, 138.6, 137.8, 136.8,
122.7, 120.8, 119.3, 114,0, 110.4, 109.7, 67.9, 61.3, 60.9,
60.8, 60.6, 54.9, 54.8, 24.7, 17.1; EIMS: m/z 486 [M]+
Synthesis of nobiletin (5,6,7,8,3′, 4′-hexamethoxyflavone,
6)
According to a similar procedure as described for the pre-
Assay for antiproliferative activity
paration of 5. 6 was obtained (yield: 80%) as yellow soild;
m.p. 112–113 °C (lit (Wang et al. 2010), 112–113 °C); H
NMR (CDCl3) δ 7.50 (dd, J = 8.5, 1.9 Hz, 1H, H-6′), 7.34
(s, 1H, H-2′), 6.92 (d, J = 8.5 Hz, 1H, H-5′), 6.55 (s, 1H, H-
3), 4.03, 3.96, 3.91, 3.89 (each, s, each 3H, –OCH3), 3.88
1
The antiproliferative activity was tested using a CCK-8
assay on Human cervix carcinoma cell line (Hela) (Xuan
et al. 2015). Briefly, cells (5 × 103 per well in a 96-well
plate) were treated with different concentrations of