116 E. Srihari et al.
Table 3 Antimalarial activity of Baylis-Hillman adducts 2–22
against CQ-sensitive P. falciparum strain (FDL-J).
2-[(2,7-Dichloro-6-fluoroquinolin-3-yl)(hydroxy)methyl]acrylo-
nitrile (12) Yield: 93%; light yellow solid; m.p. 159–120°C; H
1
NMR (300 MHz, CDCl ) δ 5.79 (s, 1H), 6.14 (s, 1H), 6.16 (s, 1H),
3
Compound Inhibitory activity Compound Inhibitory activity
7.25 (s, 1H), 7.62 (d, J=6.8 Hz, 1H), 8.11 (d, J=6.8 Hz, 1H), 8.40 (s,
1
3
(
µg/ml)
(µg/ml)
1H); C NMR (75 MHz, DMSO-d ) δ 69.4, 113.0, 113.3, 116.8,
6
1
23.8, 124.7, 125.0, 126.5, 126.6, 129.3, 133.4, 133.7, 136.8, 136.9,
IC50
IC90
IC50
IC90
143.4, 148.5, 148.6, 153.5, 156.8; IR (KBr): 3257, 3065, 2922, 2225,
-
1
1
598, 1482, 1347, 1226, 1073, 1041, 874, 816 cm ; MS (ESI):
2
3
4
5
6
7
8
9
1
1
1
0.80
4.80
0.15
0.42
0.52
0.32
0.58
0.64
0.50
0.13
2.20
8.6
19
13
14
15
16
17
18
19
20
21
22
CQ
0 .3 8
4 .0
4 .2
8 .0
2 1 .5
3 5
2 .5
3 .4
5 1
60
1 .6 5
1 2
1 .5 5
0.026
+
+
m/z=297 [M+1] ; HRMS: m/z [M+1] calculated for C H Cl FN O:
13
8
2
2
2
96.9997, found: 296.9989.
1.6
3.3
9.9
1.8
3.7
17
3.2
2.2
9.1
0 .3 8
0 .3 5
7 .4
16.5
0 .1 5
0 .5 7
0 .1 6
0.006
Methyl 2-[(2-chloroquinolin-3-yl)(hydroxy)methyl]acrylate (13)
1
Yield: 97%; creamy solid; m.p. 124–126°C; H NMR (300 MHz,
CDCl ) δ 3.62 (d, J=4.9 Hz, 1H), 3.81 (s, 3H), 5.57 (s, 1H), 5.99
3
(d, J=4.5 Hz, 1H), 6.35 (s, 1H), 7.55 (t, J=7.1 Hz, 1H), 7.71 (t,
J=7.1 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 8.36
0
1
2
1
3
(s, 1H); C NMR (75 MHz, CDCl ) δ 52.2, 69.0, 127.1, 127.2,
3
a
127.6, 127.7, 128.0, 130.5, 132.6, 137.0, 140.1, 147.0, 149.2,
166.7; IR (KBr): 3537, 3219, 3060, 2951, 1715, 1625, 1590, 1298,
aCholoroquine as standard.
-
1
+
1
145, 1060, 1030, 758 cm ; MS (ESI): m/z=278 [M+1] ; HRMS:
+
m/z [M+1] calculated for C H ClNO : 278.0583, found:
1
4
13
3
2
78.0592.
1
1
1
24.0, 124.5, 126.8, 127.3, 130.5, 131.9, 132.3, 136.7, 145.4,
47.0, 147.6; IR (KBr): 3201, 2961, 2925, 2229, 1624, 1587,
Methyl 2-[(2-chloro-7-methylquinolin-3-yl)(hydroxy)methyl]-
acrylate (14) Yield: 91%; creamy solid; m.p. 95–97°C; H NMR
-
1
497, 1387, 1310, 1178, 1074, 1040, 830 cm ; MS (ESI):
1
+
+
m/z=287 [M+1] ; HRMS: m/z [M+1] calculated for C H ClN O:
2
1
6
16
2
(
5
300 MHz, DMSO-d ) δ 2.56 (s, 3H), 3.18 (s, 1H), 3.71 (s, 1H),
6
87.0951, found: 287.0942.
.73 (s, 1H), 5.94 (s, 1H), 6.34 (s, 1H), 7.37 (d, J=8.1 Hz, 1H), 7.69
1
3
(
s, 1H), 7.74 (d, J=8.1 Hz, 1H), 8.22 (s, 1H); C NMR (100 MHz,
2
-[(2-Chloro-8-methylquinolin-3-yl)(hydroxy)methyl]acrylo-
CDCl ) δ 21.8, 52.1, 68.8, 125.1, 126.9, 127.3, 127.4, 129.3, 131.8,
136.7, 140.3, 141.1, 147.1, 149.2, 166.6; IR (KBr): 3284, 2948,
2920, 1725, 1624, 1326, 1256, 1133, 1035, 808 cm ; MS (ESI):
m/z=292 [M+1] ; HRMS: m/z [M+1] calculated for C H ClNO :
292.0740, found: 292.0745.
3
1
nitrile (9) Yield: 98%; creamy solid; m.p. 92–93°C; H NMR
-
1
(
300 MHz, CDCl +DMSO-d ) δ 2.74 (s, 3H), 5.67 (d, J=4.5 Hz,
3
6
+
+
1
H), 6.06 (s, 1H), 6.08 (s, 1H), 6.42 (d, J=3.7 Hz, 1H), 7.46 (t,
15 15 3
J=6.8 Hz, 1H), 7.57 (d, J=6.8 Hz, 1H), 7.75 (d, J=7.9 Hz, 1H),
8
1
1
1
.44 (s, 1H); 13C NMR (75 MHz, DMSO-d ) δ 17.2, 69.5, 116.7,
6
24.4, 125.9, 126.8, 127.0, 130.7, 131.8, 132.6, 135.3, 137.4,
Methyl 2-[(2-chloro-6-methoxyquinolin-3-yl)(hydroxy)methyl]-
acrylate (15) Yield: 80%; creamy solid; m.p. 105–106°C; H NMR
45.6, 146.9; IR (KBr): 3461, 2919, 2227, 1592, 1481, 1385,
1
-
1
+
329, 1172, 1055, 800, 778 cm ; MS (ESI): m/z=259 [M+1] ;
(500 MHz, CDCl ) δ 3.54 (s, 1H), 3.80 (s, 3H), 3.91 (s, 3H), 5.57 (s,
3
+
HRMS: m/z [M+1] calculated for C H ClN O: 259.0638,
found: 259.0627.
1
4
12
2
1H), 5.96 (s, 1H), 6.34 (s, 1H), 7.06 (d, J=1.9 Hz, 1H), 7.33 (dd, J=1.9,
13
9.7 Hz, 1H), 7.87 (d, J=9.7 Hz, 1H), 8.22 (s, 1H); C NMR (75 MHz,
CDCl ) δ 52.1, 55.5, 68.9, 105.1, 123.1, 127.5, 128.1, 129.2, 132.8,
3
2
-[(2,7-Dichloroquinolin-3-yl)(hydroxy)methyl]acrylonitrile
135.7, 140.2, 142.8, 146.5, 158.1, 166.6; IR (KBr): 3311, 2956, 2832,
1
-1
(
10) Yield: 97%; light yellow solid; m.p. 145–146°C; H NMR
1722, 1624, 1497, 1328, 1257, 1153, 1032, 823 cm ; MS (ESI):
+
+
(
300 MHz, CDCl +DMSO-d ) δ 5.64 (d, J=4.3 Hz, 1H), 6.08 (s,
m/z=308 [M+1] ; HRMS: m/z [M+1] calculated for C H ClNO :
3
6
15 15 4
1
H), 6.11 (s, 1H), 6.52 (m, 1H), 7.56 (dd, J=1.8, 8.8 Hz, 1H), 7.93
308.0689, found: 308.0695.
1
3
(
s, 1H), 7.96 (d, J=2.4 Hz, 1H), 8.52 (s, 1H); C NMR (75 MHz,
CDCl +DMSO-d ) δ 69.4, 116.5, 124.2, 125.4, 126.2, 127.8, 130.0,
3
6
Methyl 2-[(2-chloro-6,7-dimethoxyquinolin-3-yl)(hydroxy)meth-
yl]acrylate (16) Yield: 89%; sandy solid; m.p. 133–135°C; H NMR
1
1
32.6, 133.4, 135.6, 137.1, 146.7, 149.2; IR (KBr): 3205, 2924, 2221,
1
-
1
611, 1478, 1403, 1339, 1259, 1074, 1038, 809 cm ; MS (ESI):
(
300 MHz, CDCl ) δ 3.64 (d, J=3.0 Hz, 1H), 3.79 (s, 3H), 3.98 (s, 3H),
3
+
+
m/z=279 [M+1] ; HRMS: m/z [M+1] calculated for C H Cl N O:
1
3
9
2
2
4.00 (s, 3H), 5.59 (s, 1H), 5.94 (d, J=3.0 Hz, 1H), 6.34 (s, 1H), 7.01 (s,
2
79.0091, found: 279.0099.
13
1
5
1
H), 7.28 (s, 1H), 8.14 (s, 1H); C NMR (75 MHz, CDCl ) δ 52.1,
3
6.0, 56.1, 105.0, 106.7, 122.7, 127.3, 130.4, 135.1, 140.3, 144.1, 146.8,
50.0, 153.2, 166.7; IR (KBr): 3391, 3008, 2920, 1713, 1631, 1503,
1247, 1145, 1006, 849 cm ; MS (ESI): m/z=338 [M+1] ; HRMS: m/z
M+1] calculated for C H ClNO : 338.0795, found: 338.0791.
2
-[(2-Chloro-7-fluoroquinolin-3-yl)(hydroxy)methyl]acrylo-
-1
+
1
nitrile (11) Yield: 93%; dark brown solid; m.p. 101–102°C; H
NMR (300 MHz, CDCl +DMSO-d ) δ 5.66 (d, J=4.1 Hz, 1H), 6.05
+
[
16 17
5
3
6
(
(
s, 1H), 6.09 (s, 1H), 6.41 (d, J=4.3 Hz, 1H), 7.39 (m, 1H), 7.59
m, 1H), 7.97 (m, 1H), 8.51 (s, 1H); 1 C NMR (75 MHz, DMSO-
3
Methyl 2-[(2-chloro-5,8-dimethoxyquinolin-3-yl)(hydroxy)-
d6) δ 69.4, 111.1, 111.4, 116.8, 117.5, 117.9, 124.1, 129.8, 129.8,
31.0, 131.1, 131.6, 133.1, 137.3, 147.3, 147.5, 149.2, 161.5, 164.8;
IR (KBr): 3483, 3069, 2921, 2224, 1623, 1569, 1491, 1336, 1209,
methyl]acrylate (17) Yield: 91%; carrot orange solid; m.p.
1
1
155–157°C; H NMR (300 MHz, CDCl ) δ 3.75 (s, 1H), 3.80 (s,
3
3H), 3.96 (s, 3H), 4.01 (s, 3H), 5.54 (s, 1H), 6.00 (s, 1H), 6.34 (s,
-
1
+
1
122, 1061, 1029, 863, 809 cm ; MS (ESI): m/z=263 [M+1] ;
1H), 6.72 (d, J=8.3 Hz, 1H), 6.92 (d, J=8.3 Hz, 1H), 8.69 (s, 1H);
+
13
HRMS: m/z [M+1] calculated for C H ClFN O: 263.0387, found:
C NMR (75 MHz, CDCl ) δ 52.1, 55.6, 55.9, 69.0, 104.3, 108.2,
1
3
9
2
3
2
63.0396.
120.4, 127.5, 132.1, 132.3, 139.0, 140.2, 148.1, 148.5, 149.0,
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