Q. Wu et al. / European Journal of Medicinal Chemistry 44 (2009) 533e540
539
OCH3); 3.50 (3H, s, NCH3); Anal. Calcd for C22H22N2O4: C,
69.83; H, 5.86; N, 7.40. Found: C, 69.70; H, 5.92; N, 7.35.
74%), mp 200e201 ꢀC. FAB-MS m/z (M þ 1): 377; IR
1
1463, 1367, 1238, 1123, 997, 837, 740; H NMR (500 MHz,
(KBr): 3057, 2986, 2939, 2815, 1684, 1620, 1585, 1501,
4.1.9.2. 1-(3,4,5-Trimethoxy)phenyl-3-hydroxymethyl-9-ethyl-
b-carboline (9b). White crystals were obtained (2.9 g, 74%),
mp 154e155 ꢀC. FAB-MS m/z (M þ 1): 393; IR (KBr):
3328, 3068, 2968, 2936, 2835, 1621, 1582, 1504, 1450,
1410, 1370, 1231, 1125, 1052, 1013, 832, 742; 1H NMR
(500 MHz, CDCl3): d 8.30e8.32 (1H, d, J ¼ 10.5 Hz, H-4);
8.20 (1H, s, H-6); 7.57e7.65 (2H, m, H-5, H-8); 7.26e7.30
(1H, m, H-7); 6.86 (2H, s, PhH ); 4.73e4.74 (2H, d,
J ¼ 7.0 Hz, CH2OH); 4.02e4.07 (2H, s, NCH2CH3); 3.81
(6H, s, OCH3); 3.77 (3H, s, OCH3); 0.93e0.97 (3H, m,
NCH2CH3); Anal. Calcd for C23H24N2O4: C, 70.39; H, 6.16;
N, 7.14. Found: C, 70.28; H, 6.19; N, 7.09.
CDCl3): d 10.27 (1H, s, CHO); 8.76 (1H, s, H-4); 8.25e8.27
(1H, d, J ¼ 9.5 Hz, H-6); 7.66e7.70 (1H, m, H-5); 7.49e
7.51 (1H, d, J ¼ 9.5 Hz, H-8); 7.40e7.44 (1H, m, H-7); 6.84
(2H, s, PhH ); 3.94 (3H, s, OCH3); 3.92 (6H, s, OCH3); 3.59
(3H, s, NCH3); Anal. Calcd for C22H20N2O4: C, 70.20; H,
5.36; N, 7.44. Found: C, 69.96; H, 5.46; N, 7.35.
4.1.10.2.
1-(3,4,5-Trimethoxy)phenyl-9-ethyl-b-carboline-3-
carboxaldehyde (10b). White crystals were obtained (1.6 g,
82%), mp 209e210 ꢀC. FAB-MS m/z (M þ 1): 391; IR
(KBr): 3065, 3001, 2935, 2829, 1687, 1621, 1580, 1503,
1457, 1404, 1325, 1233, 1127, 1008, 865, 743; 1H NMR
(500 MHz, CDCl3): d 10.27 (1H, s, CHO); 8.77 (1H, s, H-
4); 8.26e8.28 (1H, d, J ¼ 9.5 Hz, H-6); 7.67e7.69 (1H, m,
H-5); 7.50e7.53 (1H, d, J ¼ 10.5 Hz, H-8); 7.39e7.43 (1H,
m, H-7); 6.84 (2H, s, PhH ); 4.07e4.12 (2H, m, NCH2CH3);
3.94 (3H, s, OCH3); 3.91 (6H, s, OCH3); 3.59 (3H, s,
NCH3); 1.12e1.15 (3H, m, NCH2CH3); Anal. Calcd for
C23H22N2O4: C, 70.75; H, 5.68; N, 7.17. Found: C, 70.51;
H, 5.79; N, 7.10.
4.1.9.3.
1-(3,4,5-Trimethoxy)phenyl-3-hydroxymethyl-9-n-
butyl-b-carboline (9c). White crystals were obtained (3.2 g,
76%), mp 127e128 ꢀC. FAB-MS m/z (M þ 1): 421; IR
(KBr): 3338, 3181, 3061, 2986, 2832, 1621, 1583, 1505,
1465, 1409, 1366, 1297, 1235, 1179, 1126, 1051, 998, 833,
739; 1H NMR (500 MHz, CDCl3): d 8.30e8.31 (1H, d,
J ¼ 10.5 Hz, H-4); 8.20 (1H, s, H-6); 7.57e7.65 (2H, m, H-
5, H-8); 7.25e7.29 (1H, m, H-7); 6.84 (2H, s, PhH ); 4.72e
4.74 (2H, d, J ¼ 7.0 Hz, CH2OH); 3.93e3.97 (2H, m,
NCH2CH2CH2CH3); 3.80 (6H, s, OCH3); 3.75 (3H, s,
OCH3); 1.31e1.39 (2H, m, NCH2CH2CH2CH3); 0.86e0.92
(2H, m, NCH2CH2CH2CH3); 0.62e0.66 (3H, m,
NCH2CH2CH2CH3); Anal. Calcd for C25H28N2O4: C, 71.41;
H, 6.71; N, 6.66. Found: C, 71.19; H, 6.81; N, 6.58.
4.1.10.3. 1-(3,4,5-Trimethoxy)phenyl-9-n-butyl-b-carboline-3-
carboxaldehyde (10c). White crystals were obtained (1.5 g,
72%), mp 150e151 ꢀC. FAB-MS m/z (M þ 1): 419; IR
(KBr): 3059, 3002, 2958, 2809, 1694, 1618, 1582, 1505,
1464, 1410, 1363, 1244, 1203, 1124, 1001, 969, 851, 754;
1H NMR (500 MHz, CDCl3): d 10.26 (1H, s, CHO); 8.76
(1H, s, H-4); 8.25e8.27 (1H, d, J ¼ 10.0 Hz, H-6); 7.64e
7.68 (1H, m, H-5); 7.49e7.51 (1H, d, J ¼ 10.5 Hz, H-8);
7.38e7.42 (1H, m, H-7); 6.84 (2H, s, PhH ); 3.98e4.02 (2H,
m, NCH2CH2CH2CH3); 3.93 (3H, s, OCH3); 3.91 (6H, s,
OCH3); 1.48e1.56 (2H, m, NCH2CH2CH2CH3); 0.96e1.06
(2H, m, NCH2CH2CH2CH3); 0.73e0.76 (3H, m,
NCH2CH2CH2CH3); Anal. Calcd for C25H26N2O4: C, 71.75;
H, 6.26; N, 6.69. Found: C, 71.62; H, 6.29; N, 6.63.
4.1.9.4. 1-(3,4,5-Trimethoxy)phenyl-3-hydroxymethyl-9-phe-
nylpropyl-b-carboline (9d). White crystals were obtained
(3.5 g, 72%), mp 124e125 ꢀC. FAB-MS m/z (M þ 1): 483; IR
(KBr): 3324, 3062, 2938, 2836, 1621, 1582, 1503, 1459, 1410,
1
1364, 1235, 1177, 1126, 1052, 838, 746; H NMR (500 MHz,
CDCl3): d 8.30e8.32 (1H, d, J ¼ 10.5 Hz, H-4); 8.21 (1H, s,
H-6); 7.56e7.63 (2H, m, H-5, H-8); 6.98e7.30 (6H, m, H-7,
PhH ); 6.87 (2H, s, PhH ); 4.73e4.74 (2H, d, J ¼ 7.0 Hz,
CH2OH); 4.03e4.05 (2H, m, NCH2CH2CH2Ph); 3.79 (9H, s,
OCH3); 2.12e2.16 (2H, m, NCH2CH2CH2Ph); 1.62e1.70
(2H, m, NCH2CH2CH2Ph); Anal. Calcd for C30H30N2O4: C,
74.67; H, 6.27; N, 5.81. Found: C, 74.76; H, 6.35; N, 5.76.
4.1.10.4. 1-(3,4,5-Trimethoxy)phenyl-9-phenylpropyl-b-carbo-
line-3-carboxaldehyde (10d). White crystals were obtained
(1.8 g, 75%), mp 174e175 ꢀC. FAB-MS m/z (M þ 1): 481; IR
(KBr): 3065, 2998, 2957, 2934, 2828, 1689, 1621, 1581,
1
1504, 1456, 1405, 1366, 1236, 1127, 1006, 746; H NMR
4.1.10. General procedure for the preparation of 1-(3,4,5-
trimethoxy)phenyl-9-substituted-b-carboline-3-
carboxaldehyde (10aed)
To a solution of 9aed (5 mmol) in CH3CN (300 ml) was
added activated MnO2 (20 mmol). The suspension was re-
fluxed for 2 h and then cooled and filtered through Celite.
The filtrate was passed through silica gel and washed with
ethyl acetate, and the solvent was removed under reduced
pressure. The residue was crystallized from acetone or ace-
tone-petroleum ether to afford white crystals.
(500 MHz, CDCl3): d 10.30 (1H, s, CHO); 8.76 (1H, s, H-4);
8.24e8.26 (1H, d, J ¼ 10.0 Hz, H-6); 7.62e7.66 (1H, m, H-
5); 7.38e7.42 (2H, m, H-7, H-8); 6.97e7.26 (5H, m, PhH );
6.85 (2H, s, PhH ); 4.05e4.09 (2H, m, NCH2CH2CH2Ph);
3.97 (3H, s, OCH3); 3.89 (6H, s, OCH3); 2.25e2.29 (2H, m,
NCH2CH2CH2Ph); 1.80e1.88 (2H, m, NCH2CH2CH2Ph);
Anal. Calcd for C30H28N2O4: C, 74.98; H, 5.87; N, 5.83. Found:
C, 74.82; H, 5.90; N, 5.79.
4.2. Cytotoxicity assays in vitro
4.1.10.1. 1-(3,4,5-Trimethoxy)phenyl-9-methyl-b-carboline-3-
carboxaldehyde (10a). White crystals were obtained (1.4 g,
Cytotoxicity assays in vitro were carried out using 96-
microtitre plate cultures and MTT staining according to the