134
U.A. Pereira et al. / European Journal of Medicinal Chemistry 82 (2014) 127e138
(15), 202 (13), 127 (15), 125 (41), 89 (14), 57 (55), 56 (17), 55 (18).
HRMS (ESI TOF-MS) calcd. for [C22H23Br2ClNO3]þ: 541.9728, found
541.9572.
7.04 (m, 2H, H-400 and H-500), 7.08 (dd, 1H, J ¼ 8.7, 2.1 Hz, H-40), 7.17
(dd, 1H, J ¼ 6.6, 2.7 Hz, H-300), 7.25 (dd, 1H, J ¼ 6.9, 2.7 Hz, H-600). 13C
NMR (75 MHz, CDCl3): d 20.5 (AreCH3), 20.7 (C-9), 20.8 (C-10), 27.8
(C-8), 38.7 (C-6), 48.2 (C-7), 56.5 (eOCH3), 93.4 (C-5), 111.5 (C-30),
120.3 (C-3)**, 121.7 (C-10)**, 126.6 (C-500), 128.3 (C-400), 129.3 (C-300),
130.4 (C-600), 131.5 (C-60), 131.5 (C-40), 131.2 (C-50), 132.8 (C-200),
135.2 (C-100), 153.6 (C-20)*, 154.1 (C-4)*, 164.7 (C-2). *, **These as-
signments could be reversed; MS, m/z (%) 354 (98), 352 (100), 298
(19), 296 (19), 145 (17), 127 (11), 125 (27), 115 (12), 57 (19). HRMS
(ESI TOF-MS) calcd. for [C23H26BrClNO3]þ: 478.0779, found
478.0804.
4.2.3.3. 3-Bromo-4-(5-bromo-2-methoxyphenyl)-5-(4-
bromobenzyl)-5-hydroxy-1-isobutylpyrrol-2(5H)-one
(11c).
Compound 11c was synthesized using a method similar to that of
11a and was isolated as white solid in 85% yield, purified by column
chromatography, eluent hexane/dichloromethane (1:7 v/v). m.p.
172.5e173.5 ꢂC. Rf ¼ 0.22 (hexane:dichloromethane, 1:7, v/v). IR
(ATR) nmax 3399e3154, 2957, 2869, 2844, 1676, 1645, 1486, 1385,
.
1247, 1050, 1026, 809, 653, 620, 506 cmꢁ1 1H NMR (300 MHz,
CDCl3):
d
0.96 (d, 3H, J ¼ 6.6 Hz, H-9), 0.98 (d, 3H, J ¼ 6.6 Hz, H-10),
4 . 2 . 3 . 6 . 3 - B ro m o - 5 - ( 2 - b ro m o b e n z yl ) - 4 - ( 5 - ch l o ro - 2 -
2.23e2.37 (m, 1H, H-8), 3.02 (d, 1H, J ¼ 14.7 Hz, H-6a), 3.11 (d, 1H,
J ¼ 14.7 Hz, H-6b), 3.13 (dd, 1H, J ¼ 14.1, 7.2 Hz, H-7a), 3.53 (dd, 1H,
J ¼ 14.1, 8.1 Hz, H-7b), 3.73 (s, 3H, eOCH3), 6.74 (d, 1H, J ¼ 8.7 Hz, H-
30), 6.83 (d, 2H, J ¼ 8.4 Hz, H-200 and H-600), 7.10 (d, 1H, J ¼ 2.7 Hz, H-
60), 7.25 (d, 2H, J ¼ 8.4 Hz, H-300 and H-500), 7.45 (dd, 1H, J ¼ 8.7,
methoxyphenyl)-5-hydroxy-1-isobutylpyrrol-2(5H)-one
(11f).
Compound 11f was synthesized using a method similar to that of
11a and was isolated as white solid in 76% yield, purified by col-
umn chromatography, eluent hexane/dichloromethane (1:9 v/v).
m.p. 159.3e160.5 ꢂC. Rf ¼ 0.31 (hexane:dichloromethane, 1:9, v/v).
IR (ATR) nmax 3221e3397, 3068, 2936, 2864, 2842, 1688, 1673,
2.7 Hz, H-40). 13C NMR (75 MHz, CDCl3):
d 20.7 (C-9), 21.0 (C-10),
28.0 (C-8), 42.3 (C-6), 48.3 (C-7), 56.5 (eOCH3), 93.5 (C-5), 113.2 (C-
30), 113.6 (C-50), 121.4 (C-400), 122.6 (C-10 and C-3), 131.2 (C-300 and C-
500), 131.6 (C-200 and C-600), 133.0 (C-100), 133.6 (C-60), 133.7 (C-40),
151.7 (C-20), 155.0 (C-4), 164.4 (C-2); MS, m/z (%) 420 (47), 418 (100),
416 (50), 364 (10), 362 (20), 360 (10), 283 (13), 281 (13), 171 (12),
169 (16), 90 (15), 89 (12), 57 (26). HRMS (ESI TOF-MS) calcd. for
[C22H22Br3NNaO3]þ: 607.9042, found 607.9052.
1486, 1411, 1390, 1239, 1137, 1046, 890, 806, 751 cmꢁ1
.
1H NMR
0.94 (d, 3H, J ¼ 6.6 Hz, H-9), 0.95 (d, 3H,
(300 MHz, CDCl3):
d
J ¼ 6.6 Hz, H-10), 2.19e2.36 (m, 1H, H-8), 3.07 (dd, 1H, J ¼ 13.8,
7.8 Hz, H-7a), 3.30 (d, 1H, J ¼ 15 Hz, H-6a), 3.41 (d, 1H, J ¼ 15 Hz, H-
6b), 3.50 (dd, 1H, J ¼ 13.8, 7.8 Hz, H-7b), 3.76 (s, 3H, eOCH3), 4.86
(s, 1H, eOH), 6.75 (d, 1H, J ¼ 9.0 Hz, H-30), 6.96 (ddd, 1H, J ¼ 7.8, 7.8,
1.8 Hz, H-400), 6.99 (d, 1H, J ¼ 2.4 Hz, H-60), 7.06 (ddd, 1H, J ¼ 7.8,
7.8, 1.5 Hz, H-500), 7.23 (dd, 1H, J ¼ 9.0, 2.4 Hz, H-40), 7.25 (dd, 1H,
J ¼ 7.8, 1.8 Hz, H-600), 7.41 (dd, 1H, J ¼ 7.8, 1.5 Hz, H-300). 13C NMR
4.2.3.4. 3-Bromo-5-(3-chlorobenzyl)-5-hydroxy-1-isobutyl-4-(5-
methyl-2-methoxyphenyl)pyrrol-2(5H)-one (11d). Compound 11d
was synthesized using a method similar to that of 11a and was
isolated as white solid in 84% yield, purified by column chroma-
tography, eluent hexane/dichloromethane (1:8 v/v). m.p. 140.0e
140.5 ꢂC. Rf ¼ 0.30 (hexane:dichloromethane, 1:8, v/v). IR (ATR)
nmax 3376e3226, 2957, 2928, 2869, 1691, 1678, 1638, 1500, 1434,
(75 MHz, CDCl3):
d 20.7 (C-9), 20.9 (C-10), 27.8 (C-8), 41.5 (C-6),
48.2 (C-7), 56.6 (eOCH3), 93.6 (C-5), 112.6 (C-30), 122.0 (C-3)*,
122.6 (C-10)*, 126.4 (C-200): 126.5 (C-50), 127.3 (C-500), 128.8 (C-400),
130.3 (C-600), 130.6 (C-60), 130.7 (C-40), 132.8 (C-300), 134.1 (C-100),
152.2 (C-20), 154.4 (C-4), 164.6 (C-2). *These assignments could be
ꢃ
ꢃ
reversed; MS, m/z (%) 529 ([Mþ6]þ e H2O, 3), 527 ([Mþ4]þ
e
1414, 1248, 1064, 1017, 882, 801, 785, 686, 656 cmꢁ1
(300 MHz, CDCl3):
.
1H NMR
0.96 (d, 3H, J ¼ 6.9 Hz, H-10), 0.99 (d, 3H,
H2O, 16), 525 ([Mþ2]þ e H2O, 24), 523 ([M]þꢃ e H2O, 10), 376 (17),
375 (16), 374 (100), 372 (73), 317 (22), 316 (16), 171 (10), 169 (14),
165 (12), 57 (18), 41 (41). HRMS (ESI TOF-MS) calcd. for
[C22H23Br2ClNO3]þ: 541.9728, found 541.9700.
ꢃ
d
J ¼ 6.9 Hz, H-9), 2.30 (s, 3H, AreCH3), 2.26e2.38 (m, 1H, H-8), 3.05
(s, 2H, H-6), 3.14 (dd, 1H, J ¼ 13.8, 7.2 Hz, H-7a), 3.55 (dd, 1H,
J ¼ 13.8, 8.1 Hz, H-7b), 3.78 (s, 3H, eOCH3), 5.37 (s, 1H, eOH), 6.75e
6.77 (m, 1H, H-200), 6.78 (d, 1H, J ¼ 9.0 Hz, H-30), 6.85 (ddd, 1H,
J ¼ 8.1, 1.5, 1.5 Hz, H-600), 6.91 (d, 1H, J ¼ 2.1 Hz, H-60), 7.05 (dd, 1H,
J ¼ 8.1, 8.1 Hz, H-500), 7.10 (ddd, 1H, J ¼ 8.1, 1.5, 1.5 Hz, H-400), 7.14 (dd,
4.2.3.7. 3-Bromo-4-(5-chloro-2-methoxyphenyl)-5-hydroxy-1-
isobutyl-5-(3-methoxybenzyl)pyrrol-2(5H)-one
(11g).
J ¼ 9.0, 2.1 Hz, H-40) 13C NMR (75 MHz, CDCl3):
d
20.6 (C-8), 20.7 (C-
Compound 11g was synthesized using a method similar to that of
11a and was isolated as white solid in 76% yield, purified by column
chromatography, eluent dichloromethane. m.p. 152.0e153.3 ꢂC.
Rf ¼ 0.20 (dichloromethane). IR (ATR) nmax 3187e3416, 3069, 3003,
2960, 2931, 2868, 2837, 1685, 1671, 1592, 1490, 1434, 1412, 1253,
9), 20.9 (C-10), 28.0 (AreCH3), 42.9 (C-6), 48.3 (C-7), 56.5 (eOCH3),
93.4 (C-5), 111.7 (C-30), 120.4 (C-3)**, 121.7 (C-10)**, 127.3 (C-400),
127.8 (C-600), 129.3 (C-500), 130.8 (C-60), 131.3 (C-50), 131.9 (C-40),
132.0 (C-200), 133.7 (C-300), 136.3 (C-100), 153.4 (C-20)*, 153.7 (C-4)*,
164.6 (C-2). *, **These assignments could be reversed. MS, m/z (%)
354 (99), 352 (100), 298 (18), 296 (19), 146 (11), 145 (17), 125 (21),
115 (13), 57 (27). HRMS (ESI TOF-MS) calcd. for [C23H26BrClNO3]þ:
478.0779, found 478.0798.
1104, 701, 655, 640 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 0.97 (d, 3H,
J ¼ 6.6 Hz, H-9), 0.98 (d, 3H, J ¼ 6.6 Hz, H-10), 2.25e2.39 (m, 1H, H-
8), 3.07 (d, 1H, J ¼ 14.7 Hz, H-6a), 3.14 (d, 1H, J ¼ 14.7 Hz, H-6b), 3.14
(dd, 1H, J ¼ 13.8, 7.2 Hz, H-7a), 3.56 (dd, 1H, J ¼ 13.8, 8.1 Hz, H-7b),
3.73 (s, 3H, eOCH3), 3.80 (s, 3H, eOCH3), 4.63 (s, 1H, eOH), 6.50 (s,
1H, H-200), 6.56 (d, 1H, J ¼ 7.8 Hz, H-400), 6.71 (m, 1H, H-600), 6.84 (d,
1H, J ¼ 8.7 Hz, H-30), 6.94 (d, 1H, J ¼ 2.4 Hz, H-60), 7.09 (dd, 1H,
J ¼ 7.8, 7.8 Hz, H-500), 7.30 (dd, 1H, J ¼ 8.7, 2.4 Hz, H-40). 13C NMR
4.2.3.5. 3-Bromo-5-(2-chlorobenzyl)-5-hydroxy-1-isobutyl-4-(5-
methyl-2-methoxyphenyl)pyrrol-2(5H)-one (11e). Compound 11e
was synthesized using a method similar to that of 11a and was
isolated as white solid in 84% yield, purified by column chroma-
tography, eluent hexane/dichloromethane (1:8 v/v). m.p. 128.3e
129.8 ꢂC. Rf ¼ 0.28 (hexane:dichloromethane, 1:8, v/v). IR (ATR)
nmax 3401e3174, 2959, 2928, 2668, 1689, 1675, 1411, 1385, 1244,
(75 MHz, CDCl3):
d 20.7 (C-9), 20.9 (C-10), 27.9 (C-8), 42.5 (C-6),
48.4 (C-7), 55.4 (eOCH3), 56.7 (eOCH3), 93.8 (C-5), 112.9 (C-30),
113.3 (C-600), 115.1 (C-200), 122.2 (C-400), 122.3 (C-3)*, 122.7 (C-10)*,
126.5 (C-50), 129.3 (C-500), 130.8 (C-40), 131.0 (C-60), 135.5 (C-100),
151.9 (C-20), 154.6 (C-300), 159.5 (C-4), 164.3 (C-2). *These assign-
ments could be reversed; MS, m/z (%) 479 ([Mþ4]þꢃ e H2O, 10), 477
1056, 806, 730, 686, 656, 620 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
0.93 (d, 3H, J ¼ 6.9 Hz, H-9), 0.95 (d, 3H, J ¼ 6.9 Hz, H-10), 2.21 (s,
ꢃ
3H, AreCH3), 2.25e2.35 (m, 1H, H-8), 3.05 (dd, 1H, J ¼ 14.1, 7.2 Hz,
H-7a), 3.26 (d, 1H, J ¼ 15.0 Hz, H-6a), 3.35 (d, 1H, J ¼ 15.0 Hz, H-6b),
3.50 (dd, 1H, J ¼ 14.1, 7.8 Hz, H-7b), 3.77 (s, 3H, eOCH3), 5.22 (s, 1H,
eOH), 6.71e6.72 (m, 1H, H-60), 6.73 (d, 1H, J ¼ 8.7 Hz, H-30), 7.01e
([Mþ2]þ e H2O, 37), 475 ([M]þꢃ e H2O, 29), 396 (15), 375 (17), 374
(100), 373 (11), 372 (76), 340 (29), 318 (25), 316 (18), 122 (25), 121
(25), 91 (15), 57 (26), 41 (44). HRMS (ESI TOF-MS) calcd. for
[C23H26BrClNO4]þ: 494.0728, found 494.0837.