X.-D. Hao et al. / European Journal of Medicinal Chemistry 102 (2015) 26e38
35
(
(
10 mL), poured into water (20 mL), and extracted with CH
3 ꢂ 15 mL). The combined organic layers were washed with water,
. After filtered, the solution was
2
Cl
2
4.1.21. (E)-1-(4-chlorobenzylidene)-2-(3,5-dimethoxyphenyl)-4,6-
dimethoxy-3-(4-methoxylphenyl)-2,3-dihydro-1H-indene(12f)
brine, and dried over MgSO
concentrated in vacuo and further purified by silica gel column
4
Compound 12f was prepared in a manner identical to that
1
described for 12a as a light yellow solid. Yield 57%; H NMR (CDCl
ppm) : 3.60 (3H, s), 3.72 (6H, s), 3.74 (3H, s), 3.91 (3H, s), 4.24 (1H,
s), 4.31 (1H, s), 6.26e6.39 (4H, m), 6.75 (2H, d, J ¼ 8.5 Hz), 6.82 (1H,
3
,
chromatography (ethyl acetate/hexanes ¼ 1/10) to give both the
d
1
desired E-alkene E-12a as a yellow solid. Yield 67%; H NMR (CDCl
3
,
1
3
ppm)
d
: 3.60 (3H, s), 3.73 (6H, s), 3.94 (3H, s), 4.37 (2H, s), 6.27e6.36
2H, m), 6.42 (2H, d, J ¼ 2.1 Hz), 6.87 (1H, d, J ¼ 1.6 Hz), 7.07e7.32
11H, m); 13C NMR (CDCl
, ppm) : 55.19, 55.54, 57.48, 58.95, 77.17,
4.87, 97.67, 99.45, 105.25, 122.86, 126.04, 126.69, 126.92, 128.19,
28.32, 128.70, 136.75, 144.48, 145.06, 145.39, 147.55, 157.40, 160.90,
s), 7.00 (2H, d, J ¼ 8.6 Hz), 7.08 (1H, s), 7.16 (4H, q, J ¼ 8.5 Hz);
C
(
(
9
NMR (CDCl , ppm) : 55.12, 55.20, 55.25, 55.55, 56.71, 59.22, 94.86,
3
d
3
d
97.66, 99.71, 105.21, 113.71, 121.51, 127.39, 127.76, 128.33, 129.86,
132.32, 135.26, 137.58, 144.60, 145.30, 147.23, 157.41, 157.88, 160.97,
þ
1
161.44; ESIMS m/z: 543.2 [M þ H] .
þ
1
4
61.44; ESIMS m/z: 478.9 [M þ H] ; C32
30 4
H O : HRMS calcd.
þ
79.2203 [M þ H] , found 479.2215.
4.1.22. (E)-1-Benzylidene-2-(3,5-dihydroxyphenyl)-3-phenyl-2,3-
dihydro-1H-indene-4,6-diol(3a)
To a solution of 12a (0.18 g, 0.37 mmol) in anhydrous CH
2
Cl
2
4
4
.1.17. (E)-1-(4-methoxylbenzylidene)-2-(3,5-dimethoxyphenyl)-
,6-dimethoxy-3-phenyl-2,3-dihydro-1H-indene(12b)
ꢁ
(
15 mL) was added BBr
3
(0.53 mL, 5.58 mmol) at 0 C under N
2
. The
resulting mixture was stirred at room temperature for 8 h. Upon
completion, the reaction mixture was quenched with water and
extracted with ethyl acetate (3 ꢂ 15 mL). The combined organic
Compound 12b was prepared in a manner identical to that
1
described for 12a as a light yellow solid. Yield 69%; H NMR (CDCl
ppm)
3
,
d: 3.58 (3H, s), 3.73 (9H, m), 3.92 (3H, s), 4.33 (2H, d,
2 4
layers were then washed with brine, dried over Na SO , filtered,
J ¼ 7.8 Hz), 6.30 (2H, s), 6.43 (2H, s), 6.73 (2H, d, J ¼ 8.6 Hz, 2H), 6.83
and evaporated. The residue was purified by Rp silica gel column
chromatography (MeOH:H
O ¼ 1:2) to give 3a as a light brown
solid. Yield 42%; H NMR (CD OD, ppm) : 4.04 (1H, s), 4.22 (1H, s),
.06 (1H, s), 6.18 (3H, s), 6.72 (1H, s), 6.99e7.24 (11H, m); C NMR
CD OD, ppm) : 58.84, 61.03, 98.62, 101.62, 104.21, 106.51, 123.35,
25.42, 127.02, 127.63, 127.95, 129.13, 129.27, 129.70, 138.39, 146.28,
13
(
5
1
1H, s), 7.10e7.22 (8H, m); C NMR (CDCl
5.80, 57.80, 59.23, 95.02, 97.93, 99.34, 105.55, 113.95, 122.69,
26.27, 126.82, 127.19, 128.58, 129.88, 130.30, 142.40, 145.65, 145.84,
3
, ppm) d: 55.44, 55.47,
2
1
3
d
13
6
(
1
þ
1
C
47.88, 157.67, 158.68, 161.20, 161.69; ESIMS m/z: 509.2 [M þ H] ;
d
þ
3
H
33 32
O
5
: HRMS calcd. 509.23280 [M þ H] , found 509.23104.
1
47.16, 147.37, 149.44, 156.30, 159.74, 159.91; ESIMS m/z: 422.9
þ
þ
[M þ H] ; C28
22
H O
4
: HRMS calcd. 423.1591 [M þ H] , found
4
3
.1.18. (E)-1-Benzylidene-2-(3,5-dimethoxyphenyl)-4,6-dimethoxy-
-(4-methoxyl phenyl)-2,3-dihydro-1H-indene(12c)
423.1580.
Compound 12c was prepared in a manner identical to that
1
described for 12a as a light yellow solid. Yield 65%; H NMR (CDCl
3
,
4.1.23. (E)-1-(4-chlorobenzylidene)-2-(3,5-dihydroxyphenyl)-3-
ppm)
d: 3.62 (3H, s), 3.74 (6H, s), 3.75 (3H, s), 3.94 (3H, s), 4.36 (2H,
(hydroxyphenyl)-2,3-dihydro-1H-indene-4,6-diol(3f)
s), 6.29e6.47 (4H, m), 6.78 (2H, d, J ¼ 8.6 Hz), 6.88 (1H, d, J ¼ 1.8 Hz),
Compound 3f was prepared in a manner identical to that
13
1
7
.05 (2H, d, J ¼ 8.6 Hz), 7.10e7.34 (6H, m); C NMR (CDCl
5.11, 55.20, 55.23, 55.55, 56.71, 50.21, 94.90, 97.64, 99.50, 105.27,
13.69, 122.88, 126.71, 127.23, 127.82, 128.22, 128.72, 136.80, 137.71,
3
, ppm)
d
:
described for 3a as a light yellow solid. Yield 39%; H NMR (CD
3
OD,
5
1
ppm)
d: 4.02 (1H, s), 4.19 (1H, s), 6.09e6.22 (4H, m), 6.62 (2H, d,
J ¼ 8.5 Hz), 6.73 (1H, d, J ¼ 1.9 Hz), 6.86 (2H, d, J ¼ 8.5 Hz), 7.03 (1H,
1
3
1
5
44.57, 144.94, 147.61, 157.40, 157.85, 160.91, 161.41; ESIMS m/z:
09.2 [M þ H] .
s), 7.15 (2H, d, J ¼ 8.6 Hz), 7.24 (2H, d, J ¼ 8.6 Hz); C NMR (CD
ppm) : 58.13, 61.17, 98.60, 101.62, 104.47, 106.42, 115.98, 121.72,
26.02, 128.84, 129.17, 131.05, 133.12, 137.19, 138.10, 146.87, 147.50,
3
OD,
þ
d
1
1
C
þ
49.12, 156.24, 156.53, 159.76, 159.82; ESIMS m/z: 473.1 [M þ H] ;
4.1.19. (E)-1-(4-methylbenzylidene)-2-(3,5-dimethoxyphenyl)-4,6-
þ
28
H
21
C
l1
O
5
: HRMS calcd. 473.1150 [M þ H] , found 473.1158.
dimethoxy-3-(4-methoxylphenyl)-2,3-dihydro-1H-indene(12d)
Compound 12d was prepared in a manner identical to that
4
5
.1.24. 3-Benzyl-2-(3,5-dihydroxyphenyl)-1-phenyl-1H-indene-
,7-diol(14a)
1
described for 12a as a light yellow solid. Yield 72%; H NMR (CDCl
3
,
ppm) d: 2.26 (3H, s), 3.60 (3H, s), 3.72 (6H, s), 3.74 (3H, s), 3.92 (3H,
Compound 14a was prepared in a manner identical to that
s), 4.31 (2H, s), 6.27e6.33 (2H, m), 6.41 (2H, d, J ¼ 2.1 Hz), 6.75 (2H,
1
described for 3a as a light yellow solid. Yield 10%; H NMR (CD
3
OD,
d, J ¼ 8.6 Hz), 6.84 (1H, d, J ¼ 1.7 Hz), 7.01 (4H, m), 7.12 (1H, s), 7.18
ppm)
m), 6.95e7.29 (10H, m); C NMR (CD
01.01, 101.33, 102.49, 108.73, 125.67, 126.98, 127.03, 128.88, 129.32,
29.42, 129.51, 137.38, 139.37, 141.11, 141.20, 149.35, 151.06, 154.10,
d
: 3.96 (2H, dd, J ¼ 15.9, 33.6 Hz), 4.91 (1H, s), 5.96e6.34 (5H,
1
3
(
5
1
1
2H, d, J ¼ 8.1 Hz); C NMR (CDCl
3
, ppm) d: 29.69, 55.13, 55.20,
13
3
OD, ppm) d: 33.11, 56.91,
5.23, 55.55, 56.72, 59.22, 94.82, 97.63, 99.32, 105.27, 113.67, 122.81,
1
1
27.07, 127.81, 128.26, 128.67, 128.96, 133.99, 136.57, 137.82, 143.52,
45.10, 147.68, 157.38, 157.80, 160.89, 161.35; ESIMS m/z: 523.2
þ
1
4
59.98, 159.02; ESIMS m/z: 422.9 [M þ H] ; C28
22 4
H O : HRMS calcd.
þ
[
M þ H] .
þ
23.1591 [M þ H] , found 423.1561.
4
.1.20. (E)-1-(4-fluorobenzylidene)-2-(3,5-dimethoxyphenyl)-4,6-
4.1.25. 3-(4-Hydroxybenzyl)-2-(3,5-dihydroxyphenyl)-1-phenyl-
1H-indene-5,7-diol(14b)
dimethoxy-3-(4-methoxyl phenyl)-2,3-dihydro-1H-indene(12e)
Compound 12e was prepared in a manner identical to that
Compound 14b was prepared in a manner identical to that
described for 3a as a light yellow solid. Yield 43%; H NMR
1
1
described for 12a as a light yellow solid. Yield 49%; H NMR (CDCl
3
,
ppm)
d
: 3.60 (3H, s), 3.72 (6H, s), 3.75 (3H, s), 3.92 (3H, s), 4.24 (1H,
(400 MHz, CD
6.07e6.24 (5H, m), 6.72 (2H, d, J ¼ 8.2 Hz), 6.97e7.15 (7H, m);
NMR (100 MHz, CD OD) 32.23, 56.82, 101.02, 101.23, 102.39,
3
OD)
d
3.90 (2H, dd, J ¼ 15.6, 34.4 Hz), 4.92 (1H, s),
13
s), 4.31 (1H, s), 6.24e6.43 (4H, m), 6.75e6.87 (5H, m), 7.01 (2H, d,
C
13
J ¼ 7.0 Hz), 7.10 (1H, s), 7.21 (2H, d, J ¼ 6.0 Hz); C NMR (CDCl
ppm) : 55.16, 55.25, 55.29, 55.59, 56.75, 59.19, 69.53, 94.95, 97.76,
9.59, 105.30, 113.76, 115.04, 115.25, 121.67, 127.84, 130.26, 130.34,
33.05, 133.08, 137.75, 144.30, 144.83, 147.44, 157.49, 157.95, 161.04,
3
,
3
d
d
108.70, 116.25, 125.67, 126.89, 128.82, 129.32, 130.30, 131.90, 137.88,
9
1
139.41, 141.22, 149.45, 150.64, 154.05, 156.56, 158.99; ESIMS m/z:
þ
þ
439.1 [M þ H] , HRMS calcd. for 439.1540 [M þ H] , found
þ
161.50; ESIMS m/z: 527.2 [M þ H] .
439.1541.