2232
Synthesis, Characterization and in vitro Anticancer Activity of Novel 8,4’-Oxyneolignan Analogues
J. Braz. Chem. Soc.
phenacyl bromide and 0.57 g (4.52 mmol) of K2CO3 and
purified by recrystallization from methanol (74% yield).
The product obtained was a white solid (mp 135-137 °C).
1H NMR (600 MHz, CDCl3) d 8.01 (d, J 7.3 Hz, 2H,Ar-H),
7.96 (d, J 7.3 Hz, 2H, Ar-H), 7.73 (d, J 16.1 Hz, 1H, CH),
7.62 (td, J1 7.3 Hz, J2 3.6 Hz, 2H,Ar-H), 7.50 (td, J1 7.8 Hz,
J2 2 Hz, 4H, Ar-H), 7.12 (d, J 1.8 Hz, 1H, Ar-H), 7.06 (dd,
J1 8.4 Hz, J2 1.8 Hz, 1H,Ar-H), 6.80 (d, J 8.4 Hz, 1H,Ar-H),
6.48 (d, J 16.1 Hz, 1H, CH), 5.47 (s, 2H, CH2), 5.40 (s, 2H,
CH2), 3.93 (s, 3H, OCH3); 13C NMR (150 MHz, CDCl3)
d 193.8, 192.4, 166.4, 149.8, 149.7, 145.8, 134.4, 134.4,
134.0, 133.9, 128.9, 128.6, 128.1, 127.8, 122.5, 115.3,
113.9, 110.8, 71.6, 66.0, 56.0. HREIMS m/z 453.1307
[M + Na]+ (calcd. for C26H22NaO6+, 453.1309).
117.7, 117.3, 114.2, 70.9, 66.3. HREIMS m/z 423.1208
[M + Na]+ (calcd. for C25H20NaO5+, 423.1203).
(E)-2-(4-Nitrophenyl)-2-oxoethyl 3-(3-(2-(4-nitrophenyl)-
2-oxoethoxy)phenyl)acrylate (5b)
Obtained according to the general procedure from
0.09 g (0.52 mmol) of 3-hydroxycinnamic acid, 0.25 g
(1.02 mmol) of p-nitrophenacyl bromide and 0.25 g
(1.84 mmol) of K2CO3 and purified by recrystallization
from methanol (45% yield). The product obtained was a
light brown crystalline solid (mp 101-103 °C). 1H NMR
(600 MHz, CDCl3) d 8.20-8.14 (m, 2H, Ar-H), 7.80-7.73
(m, 2H,Ar-H), 7.71-7.62 (m, 2H), 7.56-7.46 (m, 3H,Ar-H),
7.26 (t, J 7.8 Hz, 1H, Ar-H), 7.09 (d, J 7.7 Hz, 1H, Ar-H),
6.85 (s, 1H, Ar-H), 6.82 (d, J 8.4 Hz, 1H, Ar-H), 6.28 (d,
J 16.1 Hz, 1H, CH), 5.12 (s, 2H, CH2), 4.91 (s, 2H, CH2);
13C NMR (150 MHz, CDCl3) d 198.9, 197.4, 165.6, 157.5,
147.3, 146.3, 145.8, 135.5, 134.7, 134.4, 134.4, 134.2,
131.5, 131.4, 130.1, 128.8, 128.8, 124.0, 123.8, 122.2,
117.0, 116.8, 114.1, 72.0, 67.6. HREIMS m/z 513.0901
[M + Na]+ (calcd. for C25H18N2NaO9+, 513.0905).
( E ) - 1 - ( 4 - M e t h ox y p h e ny l ) - 1 - ox o p r o p a n - 2 - y l
3-(4-((1-(4-methoxyphenyl)-1-oxopropan-2-yl)oxy)phenyl)
acrylate (4c)
Obtained according to the general procedure from
0.10 g (0.53 mmol) of p-hydroxycinnamic acid, 0.25 g
(1.03 mmol) of 4-methoxy-8-bromopropiophenone
and 0.26 g (1.85 mmol) of K2CO3 and purified by
recrystallization from methanol (71% yield). The product
obtained was a colorless crystalline solid (mp 142-144 °C).
1H NMR (400 MHz, DMSO-d6) d 8.12 (d, J 8.8 Hz, 2H,
Ar-H), 8.05 (d, J 8.8 Hz, 2H, Ar-H), 7.70 (d, J 8.8 Hz, 2H,
Ar-H), 7.64 (d, J 16.0 Hz, 1H, CH), 7.19-7.08 (m, 4H,
Ar-H), 6.94 (d, J 8.8 Hz, 2H,Ar-H), 6.61 (d, J 16.0 Hz, 1H,
CH), 6.16-6.06 (m, 2H, CH), 3.91 (s, 3H, OCH3), 3.90 (s,
3H, OCH3), 1.59 (d, J 7.0 Hz, 3H, CH3), 1.52 (d, J 7.0 Hz,
3H, CH3); 13C NMR (100 MHz, DMSO-d6) d 196.1, 195.1,
165.8, 163.8, 163.6, 159.2, 144.9, 130.9, 130.8, 130.3,
126.9, 126.7, 126.7, 115.3, 115.0, 114.3, 114.2, 74.3, 71.2,
55.7, 18.5, 17.2. HREIMS m/z 489.1941 [M + H]+ (calcd.
for C29H29O7+, 489.1942).
2-Oxo-2-phenylethyl cinnamate (6a)
Obtained according to the general procedure from
0.38 g (2.56 mmol) of cinnamic acid, 0.50 g (2.51 mmol)
of phenacyl bromide and 0.62 g (4.52 mmol) of K2CO3
and purified by recrystallization from acetone (86% yield).
The product obtained was a colorless crystalline solid
(mp 141-143 °C). 1H NMR (600 MHz, CDCl3) d 7.96 (d,
J 7.2 Hz, 2H, Ar-H), 7.81 (d, J 16.1 Hz, 1H, CH), 7.62 (t,
J 7.2 Hz, 1H, Ar-H), 7.55 (s, 2H, Ar-H), 7.50 (t, J 7.2 Hz,
2H, Ar-H), 7.40 (s, 3H, Ar-H), 6.60 (d, J 16.1 Hz, 1H,
CH), 5.80 (s, 2H, CH2); 13C NMR (150 MHz, CDCl3)
d 192.4, 166.4, 146.3, 134.5, 134.4, 134.0, 130.7, 129.1,
129.0, 128.4, 128.0, 117.2, 66.3. HREIMS m/z 289.0836
[M + Na]+ (calcd. for C17H14NaO3+, 289.0836).
3-[3-(2-Oxo-2-phenyl-ethoxy)-phenyl]-acrylic acid (5a)
Obtained according to the general procedure from
0.42 g (2.56 mmol) 3-hydroxycinnamic acid, 1.00 g
(5.02 mmol) of phenacyl bromide and 1.24 g (9.00 mmol)
of K2CO3 and purified by recrystallization from methanol
(76% yield). The product obtained was a white crystalline
solid (mp 139-141 °C).1H NMR (600 MHz, CDCl3) d 8.02
(d, J 7.3 Hz, 2H, Ar-H), 7.96 (d, J 7.3 Hz, 2H, Ar-H), 7.76
(d, J 16.0 Hz, 1H, CH), 7.59-7.68 (m, 2H,Ar-H), 7.48-7.56
(m, 4H, Ar-H), 7.32 (t, J 8.0 Hz, 1H, Ar-H), 7.19 (d,
J 8.0 Hz, 1H,Ar-H), 7.12 (s, 1H,Ar-H), 7.00 (dd, J1 8.0 Hz,
J2 2.2 Hz, 1H, Ar-H), 6.57 (d, J 16.0 Hz, 1H, CH), 5.47 (s,
2H, CH2), 5.32 (s, 2H, CH2); 13C NMR (150 MHz, CDCl3)
d 194.1, 192.4, 166.3, 158.5, 145.9, 135.9, 134.6, 134.4,
134.1, 134.0, 130.2, 129.0, 129.0, 128.2, 128.0, 122.0,
2-(4-Nitrophenyl)-2-oxoethyl cinnamate (6b)
Obtained according to the general procedure from
0.38 g (2.59 mmol) of cinnamic acid, 0.62 g (2.54 mmol) of
4-nitrophenacyl bromide and 0.63 g (4.56 mmol) of K2CO3
and purified by recrystallization from acetone/hexane (75%
yield). The product obtained was a light yellow crystalline
solid (mp 157-158 °C).1H NMR (600 MHz, CDCl3) d 8.36
(d, J 8.8 Hz, 2H, Ar-H), 8.12 (d, J 8.8 Hz, 2H, Ar-H), 7.81
(d, J 16.0 Hz, 1H, CH), 7.52-7.63 (m, 2H,Ar-H), 7.36-7.45
(m, 3H, Ar-H), 6.58 (d, J 16.0 Hz, 1H, CH), 5.46 (s, 2H,
CH2); 13C NMR (150 MHz, CDCl3) d 191.3, 166.1, 150.7,
146.7, 138.8, 134.1, 130.7, 129.0, 129.0, 128.3, 127.9,
124.1, 116.4, 66.2. HREIMS m/z 334.0696 [M + Na]+
(calcd. for C17H13NNaO5+, 334.0686).