STEROID SULFATASE INHIBITION
453
3079; PMR spectrum (200 MHz, DMSO, d, ppm, J/
4-Oxo-2-phenyl-4H-chromen-7-yl
dimethylphosphate 4e
Yield 68%, mp 97–998C; IR (neat, m, cm21
Hz) 6.88 (1H, s, CH), 6.91 (1H, d, J 5 8.8, Ar-H),
6.98 (1H, s, Ar-H), 7.38 (2H, t, J 5 8.5, Ar-H), 7.86
(1H, d, J 5 8.8, Ar-H), 8.09–8.14 (2H, m, Ar-H),
10.84 (1H, s, OH); 13C NMR spectrum (125 MHz,
DMSO, d, ppm) 56.7, 103.2, 107.2, 115.8, 116.8 (d,
JF-C 5 22.4), 127.2, 128.5, 129.5 (d, JF-C 5 9.2),
158.1, 161.6, 163.5, 165.7 (d, JF-C 5 249.8), 177.0.
)
670, 767, 861, 889, 966, 1039, 1148, 1278, 1570,
1613, 1637, 2856, 2960, 3074; PMR spectrum (200
MHz, CDCl3, d, ppm, J/Hz) 3.91 (6H, d, J 5 11.2,
CH3), 6.82 (1H, s, CH), 7.26 (1H, d, J 5 8.3, Ar-H),
7.51 (4H, d, J 5 6.3, Ar-H), 7.90 (2H, d, J 5 6.3, Ar-
H), 8.20 (1H, d, J 5 8.8, Ar-H); 13C NMR spectrum
(125 MHz, CDCl3, d, ppm) 55.5 (d, JP-C 5 6.1),
107.7, 109.2 (d, JP-C 5 4.4), 118.2 (d, JP-C 5 5.7),
121.3, 126.6, 127.9, 129.3, 131.6, 132.1, 154.8 (d, JP-
C 5 6.6), 157.2, 164.1, 177.8; 31P NMR spectrum
(202 MHz, CDCl3, d, ppm) 23.78. Anal. Calcd for:
C17H15O6P: C, 58.97; H, 4.37. Found: C, 59.01; H,
4.39.
7-Hydroxy-2-(4-trifluoromethylphenyl)-4H-chromen-
4-one 3c
Yield 88%, mp 249–2518C; IR (neat, m, cm21
)
1097, 1224, 1320, 1416, 1507, 1559, 1623, 2830,
3062; PMR spectrum (200 MHz, DMSO, d, ppm, J/
Hz) 6.92–6.96 (1H, m, Ar-H), 7.00–7.05 (2H, m, Ar-
H, CH), 7.86-7.94 (3H, m, Ar-H), 8.27 (2H, d, J 5
8.3, Ar-H), 10.90 (1H, s, OH); 13C NMR spectrum
(125 MHz, DMSO, d, ppm) 103.3, 108.8, 116.0,
116.8, 125.6 (d, JF-C 5 272.2), 126.6 (q, JF-C 5 4.0),
127.3, 127.7, 131.9 (q, JF-C 5 32.0), 135.9, 158.2,
160.9, 163.7, 177.0.
2-(4-Fluorophenyl)-4-oxo-4H-chromen-7-yl
dimethylphosphate 4f
Yield 54%, mp 145–1478C; IR (neat, m, cm21
)
670, 768, 836, 890, 968, 1029, 1153, 1236, 1285,
1511, 1612, 1636, 2856, 2920, 2962, 3081; PMR spec-
trum (200 MHz, CDCl3, d, ppm, J/Hz) 3.93 (6H, d,
J 5 11.7, CH3), 6.81 (1H, d, J 5 6.8, CH), 7.21–7.28
(3H, m, Ar-H), 7.54 (1H, s, Ar-H), 7.93 (2H, dd,
J 5 8.8, Ar-H), 8.23 (1H, d, J 5 8.8, Ar-H); 13C NMR
spectrum (125 MHz, CDCl3, d, ppm) 55.5 (d, JP-
C 5 6.1), 107.5, 109.1 (d, JP-C 5 4.8), 116.6 (d, JF-
C 5 22.4), 118.3 (d, JP-C 5 6.1), 121.2, 127.8, 128.0,
128.8 (d, JF-C 5 8.8), 154.8 (d, JP-C 5 6.6), 157.1,
163.2, 166.1 (d, JF-C 5 253.8), 177.7; 31P NMR spec-
trum (202 MHz, CDCl3, d, ppm) 23.68. Anal. Calcd
for: C17H14FO6P: C, 56.05; H, 3.87. Found: C, 56.09;
H, 3.91.
7-Hydroxy-2-(p-tolyl)-4H-chromen-4-one 3d
Yield 89%, mp 282–2858C; IR (neat, m, cm21
)
1093, 1223, 1389, 1414, 1509, 1562, 1622, 2835,
3065; PMR spectrum (200 MHz, DMSO, d, ppm, J/
Hz) 2.38 (3H, s, CH3), 6.85 (1H, s, CH), 6.92 (1H,
dd, J 5 8.8, Ar-H), 6.99 (1H, d, J 5 2.0, Ar-H), 7.36
(2H, d, J 5 8.3, Ar-H), 7.86 (1H, d, J 5 8.8, Ar-H),
7.95 (1H, d, J 5 8.3, Ar-H), 10.82 (1H, s, OH); 13C
NMR spectrum (125 MHz, DMSO, d, ppm) 21.7,
103.2, 106.6, 115.6, 116.8, 126.8, 127.2, 129.1, 130.3,
142.4, 158.1, 162.7, 163.4, 177.1.
General Method for the Synthesis of Dimethyl
Phosphate Derivatives 4e-4h
4-Oxo-2-(4-trifluoromethylphenyl)-4H-chromen-7-yl
dimethylphosphate 4g
To an ice-cooled solution of phosphoryl chloride
(92 mg, 0.6 mmol) in dry THF (10 mL) was added
dropwise a solution of the corresponding 7-hydroxy-
flavone derivative (3a-3d) (0.6 mmol) in THF, fol-
lowed by triethylamine (61 mg, 0.6 mmol). The reac-
tion mixture was stirred under nitrogen for 1 h. The
triethylamine hydrochloride precipitate was removed
Yield 48%, mp 161–1648C; IR (neat, m, cm21
)
770, 830, 844, 873, 1014, 1034, 1115, 1319, 1440,
1644, 2864, 2966, 3082; PMR spectrum (200 MHz,
DMSO, d, ppm, J/Hz) 3.86 (6H, d, J 5 11.7, CH3),
7.21 (1H, s, CH), 7.39 (1H, dd, J 5 8.8, Ar-H), 7.72
(1H, d, J 5 1.0, Ar-H), 7.94 (2H, d, J 5 8.3, Ar-H),
by filtration and sodium methoxide (81 mg, 1.5 8.10 (1H, d, J 5 8.8, Ar-H), 8.35 (2H, d, J 5 8.3, Ar-
H); 13C NMR spectrum (125 MHz, DMSO, d, ppm)
mmol) (freshly prepared by the addition of absolute
methanol to 60% NaH dispersed in mineral oil) was 56.0 (d, JP-C 5 6.1), 109.2, 110.1 (d, JP-C 5 4.8), 119.0
added. The reaction mixture was stirred for 1 h, and (d, JP-C 5 4.8), 121.4, 124.5 (q, JF-C 5 272.2), 126.6
a precipitate of NaCl was formed. The solution was (q, JF-C 5 3.5), 127.8, 128.0, 132.1 (q, JF-C 5 32.0),
filtered, and the solvent evaporated. The resulting 135.5, 154.9 (d, JP-C 5 6.1), 157.1, 161.8, 177.0; 31P
residue was purified by column chromatography NMR spectrum (202 MHz, DMSO, d, ppm) 23.64.
using CHCl3 as an eluent to give the desired Anal. Calcd for: C18H14F3O6P: C, 52.19; H, 3.41.
products.
Found: C, 52.22; H, 3.39.
Drug Dev. Res.