Arch. Pharm. Pharm. Med. Chem. 2004, 337, 634−644
Stilbene-Based Inhibitors of Estrone Sulfatase 641
OCH3), 4.67 (t, 3J = 7.2 Hz, 1H, -CO-CH-CH2-), 6.83 and
7.22 (AAЈBBЈ, 3J = 8.7 Hz, 4H, ArH), 6.97 and 7.99 (AAЈBBЈ,
3J = 8.9 Hz, 4H, ArH).
CH2-), 1.44 and 1.84 (d, 3J = 6.6 Hz, 3H, C=CH-CH3),
1.58Ϫ2.01 (m, 2H, C=C-CH-CH2-), 2.45 (t, 3J = 7.3 Hz, 4H,
-CH2-S-CH2-), 3.67 and 3.72 (3H, OCH3), 3.697 and 3.702
(s, 3H, OCH3), 3.36Ϫ3.39 (m, 1H, C=C-CH-CH2-), 5.48Ϫ5.56
(m, 1H, C=CH-CH3), 6.71 and 7.08 (m, 8H, ArH).
(+/Ϫ)-1-(4-Methoxyphenyl)-2-(3-methoxyphenyl)-12-pentyl-
sulfonyldodecan-1-one (10f)
(E/Z)(+/Ϫ)-3-(3-Methoxyphenyl)-4-(4-methoxyphenyl)-14-
pentylthiotetradec-4-ene (11e)
Colorless oil, yield 80%. 1H-NMR δ = 0.87 (t, 3J = 7.5 Hz,
3H, -CH2-CH3), 1.15Ϫ1.37 (m, 18H, -(CH2)2-CH3 and -SO2-
(CH2)2-(CH2)7-), 1.62Ϫ1.69 (m, 4H, -CH2-CH2-S-CH2-CH2-),
1.62Ϫ2.07 (m, 2H, -CO-CH-CH2-), 3.03 (t, 3J = 7.7 Hz, 4H,
-CH2-SO2-CH2-), 3.70 (s, 3H, OCH3), 3.80 (s, 3H, OCH3),
4.71 (t, 3J = 7.1 Hz, 1H, -CO-CH-CH2-), 6.74Ϫ7.22 (m, 4H,
Colorless oil, yield 33%. 1H-NMR δ = 0.43 (t, 3J = 7.4 Hz)
and 0.56 (t, 3J = 7.2 Hz) (3H, C=C-CH-CH2-CH3), 0.82 and
0.85 (t, 3J = 7.3 Hz, 3H, -(CH2)4-CH3), 1.14Ϫ1.36 (m, 18H,
-(CH2)2-CH3, -S-(CH2)2-(CH2)7-), 1.42Ϫ1.60 (m, 4H, -CH2-
CH2-S-CH2-CH2-), 1.61Ϫ2.08 (m, 2H, =C-CH-CH2-CH3),
2.44 and 2.45 (t, 3J = 7.6 Hz, 4H, -CH2-S-CH2-), 3.32Ϫ3.35
(m, 1H, C=C-CH-CH2-CH3), 3.59 and 3.68 (s, 3H, OCH3),
3.70 and 3.80 (s, 3H, OCH3), 4.48Ϫ4.67 (m, 1H, C=CH-
(CH2)9-), 6.37Ϫ8.04 (m, 8H, ArH).
3
ArH), 6.98 and 8.01 (AAЈBBЈ, J = 8.9 Hz, 4H, ArH).
(+/Ϫ)-1,2-Bis-(4-methoxyphenyl)-12-pentylsulfonyldodecan-
1-one (10g)
Colorless oil, yield 86%. 1H-NMR δ = 0.87 (t, 3J = 6.9 Hz,
3H, -CH2-CH3), 1.15Ϫ1.38 (m, 18H, -(CH2)2-CH3 and
-S-(CH2)2-(CH2)7-), 1.58Ϫ1.66 (m, 4H, -CH2-CH2-S-CH2-
CH2-), 1.58Ϫ2.06 (m, 2H, -CO-CH-CH2-), 3.03 (t, 3J = 7.8
Hz, 4H, -CH2-S-CH2-), 3.68 (s, 3H, OCH3), 3.80 (s, 3H,
OCH3), 4.67 (t, 3J = 7.2 Hz, 1H, -CO-CH-CH2-), 6.83 and
7.22 (AAЈBBЈ, 3J = 8.7 Hz, 4H, ArH), 6.97 and 7.99 (AAЈBBЈ,
3J = 8.9 Hz, 4H, ArH).
(E/Z)(+/Ϫ)-3-(4-Methoxyphenyl)-4-(3-methoxyphenyl)-14-
pentylsulfonyltetradec-2-ene (11f)
Colorless oil, yield 73%. 1H-NMR δ = 0.87 (t, 3J = 7.1 Hz,
3H, -(CH2)4-CH3), 1.20Ϫ1.37 (m, 18H, -(CH2)2-CH3, -S-
(CH2)2-(CH2)7-), 1.46 (d, 3J = 6.7 Hz) and 1.86 (d, 3J = 6.9
Hz) (3H, C=CH-CH3), 1.63Ϫ1.69 (m, 4H, -CH2-CH2-SO2-
CH2-CH2-), 1.63Ϫ2.10 (m, 2H, -CH2-CH-C=C), 3.03 (t, 3J =
7.7 Hz, 4H, -CH2-SO2-CH2-), 3.56 (t, 3J = 8.4 Hz, 1H, -CH2-
CH-C=C), 3.68 and 3.71 (s, 3H, OCH3), 3.72 and 3.84 (s,
3H, -OCH3), 5.57Ϫ5.61 (m, 1H, C=CH-CH3), 6.61Ϫ7.24 (m,
8H, ArH).
General procedure for introduction of the second side chain
Following start of the reaction by addition of an iodine crystal
or local heating, a solution of 5.0 mmol alkyl halide in dry
Et2O (10 mL) was added dropwise to Mg turnings (5.0 mmol)
in dry Et2O (10 mL). After addition, the mixture was kept
refluxing for 1 h. After cooling, a solution of the ketone 2
(5 mmol) in dry Et2O (10 mL) was added slowly, followed by
heating (2 h) under reflux. After cooling and dropwise addition
of 2N HCl, the mixture was extracted three times with THF.
The combined organic layers were washed with NaHCO3
solution and water, and dried (MgSO4). Following evaporation
of the solvent, the residue was purified by chromatography.
(E/Z)(+/Ϫ)-3,4-Bis-(4-methoxyphenyl)-14-pentylsulfonyl-
tetradec-2-ene (11g)
Colorless oil, yield 54%. 1H-NMR δ = 0.87 (t, 3J = 6.9 Hz,
3H, -(CH2)4-CH3), 1.15Ϫ1.38 (m, 18H, -(CH2)2-CH3, -SO2-
(CH2)2-(CH2)7-), 1.58Ϫ1.70 (m, 4H, -CH2-CH2-SO2-CH2-
CH2-), 1.44 (d, 3J = 6.6 Hz) and 1.86 (d, 3J = 6.8 Hz) (3H,
3
C=CH-CH3), 1.58Ϫ1.99 (m, 2H, C=C-CH-CH2-), 3.03 (t, J =
7.7 Hz, 4H, -CH2-SO2-CH2-), 3.68 and 3.72 (s, 3H, OCH3),
3.698 and 3.704 (s, 3H, OCH3), 3.33Ϫ3.43 (m, 1H, C=C-CH-
CH2-), 5.53Ϫ5.56 (m, 1H, C=CH-CH3), 6.65 and 7.01 (m,
8H, ArH).
(E/Z)(+/Ϫ)-3-(4-Methoxyphenyl)-4-(3-methoxyphenyl)hex-2-
ene (11a)
Colorless oil, yield 58%. 1H-NMR δ = 0.82 (t, 3J = 7.3 Hz,
3H, -CH-CH2-CH3), 1.47 and 1.87 (d, J = 6.7 Hz, 3H, =CH-
CH3), 1.57Ϫ1.81 (m, 2H, -CH-CH2-CH3), 3.33Ϫ3.41 (m, 1H,
-CH-CH2-CH3), 3.68 (s, 3H, OCH3), 3.71 (s, 3H, OCH3),
5.56Ϫ5.65 (m, 1H, =CH-CH3), 6.61Ϫ7.21 (m, 8H, ArH).
3
(E/Z)(+/Ϫ)-3-(3-Methoxyphenyl)-4-(4-methoxyphenyl)-14-
pentylsulfonyltetradec-4-ene (11h)
Prepared by oxidation of 3e with meta-chloroperbenzoic acid.
Colorless oil, yield 76%. 1H-NMR δ = 0.43 (t, 3J = 6.2 Hz)
and 0.55 (t, 3J = 7.3 Hz) (3H, C=C-CH-CH2-CH3), 0.87 (t, 3J =
7.1 Hz, 3H, -(CH2)4-CH3), 1.18Ϫ1.33 (m, 18H, -(CH2)2-CH3,
-SO2-(CH2)2-(CH2)7-), 1.64Ϫ1.73 (m, 4H, -CH2-CH2-SO2-
CH2-CH2-), 1.63Ϫ2.23 (m, 2H, C=C-CH-CH2-CH3),
3.31Ϫ3.34 (m, 1H, C=C-CH-CH2-CH3), 3.04 (t, 3J = 7.5 Hz,
4H, -CH2-SO2-CH2-), 3.59 and 3.68 (s, 3H, OCH3), 3.73 and
(E/Z)-3-(4-Methoxyphenyl)-4-(3-methoxyphenyl)-14-pentyl-
thiotetradec-3-ene (11c)
Colorless oil, yield 76%. 1H-NMR δ = 0.39 (t, 3J = 7.4 Hz)
and 0.69 (t, 3J = 7.1 Hz) (3H, =C-CH2-CH3), 0.85 (t, 3J =
6.8 Hz, 3H, -(CH2)4-CH3), 1.12Ϫ1.36 (m, 18H, -(CH2)2-CH3,
S-(CH2)2-(CH2)7-), 1.41Ϫ1.94 (m, 8H, -CH2-CH2-S-CH2-CH2-,
-CH2-C=C-CH2-), 2.44 (t, 3J = 7.1 Hz, 4H, -CH2-S-CH2-), 3.59
and 3.69 (s, 3H, OCH3), 3.73 and 3.75 (s, 3H, -OCH3),
6.38Ϫ7.36 (m, 8H, ArH).
3
3.75 (s, 3H, OCH3), 4.64 (t, J = 7.3 Hz, 1H, C=CH-(CH2)9-),
6.38Ϫ8.02 (m, 8H, ArH).
The aromatic methoxy groups were cleaved with BBr3, as
described previously [20]. Analytical data are only given for
the main products 12 and not for the isomeric byproducts 13.
(E/Z)(+/Ϫ)-3,4-Bis-(4-methoxyphenyl)-14-pentylthiotetradec-
2-ene (11d)
(E/Z)-3-(4-Hydroxyphenyl)-4-(3-hydroxyphenyl)hex-3-ene
(12a)
Colorless oil, yield 66%. 1H-NMR δ = 0.85 (t, 3J = 7.0 Hz,
3H, -(CH2)4-CH3), 1.19Ϫ1.33 (m, 18H, -(CH2)2-CH3, -S-
(CH2)2-(CH2)7-), 1.43Ϫ1.74 (m, 4H, -CH2-CH2-S-CH2-
Colorless crystals, mp 128Ϫ129°C, yield 78%. 1H-NMR δ =
0.71 and 0.73 (t, 3J = 7.4 Hz, 3H, C=C-CH2-CH3), 0.88 (t,
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