DNA Binding of γ-Carboliniums and Benzologues
J . Org. Chem., Vol. 61, No. 16, 1996 5597
100), 209 (47), 195 (46). Anal. Calcd for C14H14N2: C, 79.97;
H, 6.71; N, 13.22. Found: C, 79.68; H, 6.66;N, 13.60.
5H-P ir id o[4,3-b]in d ole (20a ): mp 230-231 °C (CH3CN,
cream-colored needles) (lit.51 mp 230-231 °C, MeOH/H2O).
7,8-Dim eth yl-5H-p yr id o[4,3-b]in d ole (20b): mp 250-251
°C (CH3CN, cream-colored needles) (lit.51 mp 251-252 °C
(EtOH/H2O)).
1,3-Dim eth yl-5H-p yr id o[4,3-b]in d ole (20c): mp 241-242
°C (EtOAc/EtOH, cream-colored powder) (lit.52 mp 241-242
°C (EtOH/H2O)).
1,3,7,8-Tetr a m eth yl-5H-p yr id o[4,3-b]in d ole (20d ): mp
296-297 °C (CH3CN, cream-colored powder); IR (KBr) νmax
2921, 1607, 1579, 1465, 1292, 1276, 1227, 1166 cm-1; 1H NMR
(DMSO-d6) δ 11.24 (bs, 1H), 7.79 (s, 1H, H9), 7.26 (s, 1H, H6),
7.06 (s, 1H, H4), 2.83 (s, 3H), 2.50 (s, 3H), 2.37 (s, 3H), 2.36 (s,
3H) ppm; MS (EI): m/ z (rel int) 224 (M+, 100), 223 (36), 209
(37). Anal. Calcd for C15H16N2: C, 80,32; H, 7.19; N, 12.49.
Found: C, 80.57; H, 7.29; N, 12.76.
(s, 1H, H11), 8.05-7.97 (m, 2H, H7 and H10), 7.87 (s, 1H, H6),
7.47 (t, 1H, H8, J 8-7 ) 8.1 Hz, J 8-9 ) 7.0 Hz), 7.38 (t, 1H, H9,
J 9-8 ) 7.0 Hz, J 9-10 ) 8.3 Hz), 7.27 (s, 1H, H4), 2.59 (s, 3H)
ppm; MS (EI) m/ z (rel int) 232 (M+, 100), 204 (15). Anal. Calcd
for C16H12N2: C, 82.73; H, 5.21; N, 12.06. Found: C, 82.45;H,
5.14; N, 12.37.
5H-Ben zo[f]p yr id o[4,3-b]in d ole (24): mp 281-282 °C
(MeOH/H2O, brown powder); IR (KBr) νmax 2715, 1608, 1576,
1
1484, 1267, 1241 cm-1; H NMR (DMSO-d6) δ 11.65 (bs, 1H),
9.41 (s, 1H, H1), 8.79 (s, 1H, H11), 8.47 (d, 1H, H3, J 3-4 ) 5,6
Hz), 8.07 (d, 1H, H10, J 10-9 ) 8.3 Hz), 8.03 (d, 1H, H7, J 7-8
)
8.1 Hz), 7.93 (s, 1H, H6), 7.49 (ddd, 1H, H8, J 8-7 ) 8.1 Hz, J 8-9
) 6,8 Hz, J 8-10 ) 1.8 Hz), 7.44-7.39 (m, 2H, H4 and H9) ppm;
13C NMR (DMSO-d6) δ 146.54, 146.32, 142.97, 139.01, 132.45,
128.23, 128.08, 127.06, 125.27, 123.01, 122.94, 119.12, 119.00,
105.96 ppm; MS (EI) m/ z (rel int) 218 (M+, 100), 190 (14),
163 (13), 109 (42). Anal. Calcd for C15H10N2: C, 82.55; H,
4.62; N, 12.83: Found: C, 82.35; H, 4.60; N, 13.05.
13H-Ben z[5,6]in d olo[3,2-c]qu in olin e (25a ): mp 342-343
°C (MeOH/H2O, brown powder); IR (KBr) υmax 3028, 1588,
1567, 1514, 1487, 1449, 1362, 1261, 1240, 1220 cm-1; 1H NMR
(DMSO-d6) δ 12.68 (bs, 1H), 9.68 (s, 1H, H6), 8.88 (s, 1H, H7),
11H-In d olo[3,2-c]qu in olin e (21a ): mp 336-337 °C (CH3-
CN, cream-colored powder) (lit.52 mp 333 °C (MeOH)).
6-Meth yl-11H-in d olo[3,2-c]qu in olin e (21b): mp 295-296
°C (CH3CN, cream-colored powder) (lit.49 mp 298 °C, MeOH);
IR (KBr) νmax 3042, 1563, 1514, 1453, 1360, 1319, 1247, 1208
8.56 (d, 1H, H4, J 4-3 ) 7.7 Hz), 8.16-8.10 (m, 4H, H1, H8, H11
,
1
cm-1; H NMR (DMSO-d6) δ 12.70 (bs, 1H, NH), 8.46 (d, 1H,
and H12), 7.81-7.68 (m, 2H, H2 and H3), 7.53-7.42 (m, 2H,
H9 and H10) ppm; 13C NMR (DMSO-d6) δ 146.48, 144.88,
143.49, 138.73, 131,88, 129.70, 128.90, 128.66, 128.29, 127.47,
125.79, 125.04, 123.92, 123.36, 122.63, 118.26, 116.76, 113.87,
106.87 ppm; MS (EI) m/ z (rel int) 268 (M+, 100), 240 (10).
Anal. Calcd for C19H12N2: C, 85.05; H, 4.51; N, 10.44.
Found: C, 84.97; H, 4.65; N, 10.38.
6-Meth yl-13H-ben z[5,6]in dolo[3,2-c]qu in olin e (25b): mp
330-331 °C (CH3CN, cream-colored powder); IR (KBr) νmax
3432, 3051, 1627, 1569, 1518, 1430, 1367, 1250 cm-1; 1H NMR
(DMSO-d6) δ 12.65 (bs, 1H), 8.78 (s, 1H, H7), 8.51 (d, 1H, H4,
J 4-3 ) 8.0 Hz), 8.19 (d, 1H, H8, J 8-9 ) 7.9 Hz), 8.13-8.09 (m,
2H, H11 and H12), 8.06 (d, 1H, J 1-2 ) 8.4 Hz), 7.74 (t, 1H, H2,
J 2-1 ) 8.4 Hz, J 2-3 ) 7.1 Hz), 7.63 (t, 1H, H3, J 3-2 ) 7.1 Hz,
J 3-4 ) 8.0 Hz), 7.52-7.42 (m, 2H, H9 and H10), 3.17 (s, 3H)
ppm; MS (EI) m/ z (rel int) 282 (M+, 100). Anal. Calcd for
C20H14N2: C, 85.08; H, 5.00; N, 9.92. Found: C, 84.90; H, 5.12;
N, 9.98.
H4, J 4-3 ) 8.0 Hz), 8.21 (d, 1H, H7, J 7-8 ) 7.7 Hz), 8.02 (d, 1H,
H1, J 1-2 ) 8.1 Hz), 7.72-7.65 (m, 2H, H2 and H10), 7.60 (t, 1H,
H3, J 3-4 ) 8.0 Hz, J 3-2 ) 7.1 Hz), 7.48 (t, 1H, H9, J 9-8 ) 7.3
Hz, J 9-10 ) 7.8 Hz), 7.32 (t, 1H, H8, J 8-7 ) 7.7 Hz, J 8-9 ) 7.3
Hz), 3.06 (s, 3H) ppm; 13C NMR (DMSO-d6) δ 154.21, 144.86,
139.82, 138.69, 128.62, 127.94, 124.93, 124.78, 122.26, 121.72,
121.50, 120.56, 116.18, 112.88, 111.72, 24.45 ppm; MS (EI) m/ z
(rel int) 232 (M+, 100), 231 (24), 204 (11). Anal. Calcd for
C16H12N2: C, 82.73; H 5.21; N 12.06. Found: C, 82.53; H, 5.35;
N, 12.12.
8,9-Dim eth yl-11H-in dolo[3,2-c]qu in olin e (21c): mp 360-
361 °C (EtOH, cream-colored prisms); IR (KBr) νmax 2922, 1630,
1570, 1514, 1504, 1466, 1362, 1279, 1258, 1245 cm-1; 1H NMR
(DMSO-d6) δ 12.45 (bs, 1H), 9.48 (s, 1H, H6), 8.46 (d, 1H, H4,
J 4-3 ) 7.7 Hz), 8.08 (d, 1H, H1, J 1-2 ) 8.2 Hz), 8.04 (s, 1H,
H7), 7.69-7.63 (m, 2H, H2 and H3), 7.47 (s, 1H, H10), 2.42 (s,
3H), 2.40 (s, 3H) ppm; MS (EI) m/ z (rel int) 246 (M+, 100),
245 (44). Anal. Calcd for C17H14N2: C, 82.90; H, 5.73; N,
11.37. Found: C, 83.24;H, 5.61; N, 11.15.
Gen er a l P r oced u r e for th e N-Meth yla tion of γ-Ca r bo-
lin e Der iva tives. To a suspension of the γ-carboline deriva-
tive (1 mmol) in acetonitrile (20 mL) was added methyl iodide
(0.62 mL, 10 mmol), and the reaction mixture was stirred at
room temperature (reflux was necessary for 27d ) for the time
indicated below. The precipitate obtained was isolated by
filtration and purified by recrystallization.
6,8,9-Tr im et h yl-11H-in d olo[3,2-c]q u in olin e (21d ): mp
330-331 °C (EtOH, cream-colored prisms); IR (KBr) νmax 2954,
2799, 1566, 1516, 1390, 1351, 1269, 1249, 1209, 1116 cm-1
;
1H NMR (DMSO-d6) δ 12.44 (bs, 1H, 8.43 (dd, 1H, H4, J 4-3
)
8.0 Hz, J 4-2 ) 1.6 Hz), 7.99 (d, 1H, H1, J 1-2 ) 8.2 Hz), 7.95 (s,
1H, H7), 7.64 (ddd, 1H, H2, J 2-1 ) 8.2 Hz, J 2-3 ) 6,9 Hz, J 2-4
) 1.6 Hz), 7.57 (ddd, 1H, H3, J 3-4 ) 8.0 Hz, J 3-2 ) 6.9 Hz,
J 3-1 ) 1.5 Hz), 7.47 (s, 1H, H10), 3.04 (s, 3H), 2.42 (s, 6H) ppm;
MS (EI) m/ z (rel int) 260 (M+, 100), 259 (33), 245 (29). Anal.
Calcd for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found: C,
82.74; H, 6.46; N, 10.45.
2-Meth yl-5H-p yr id o[4,3-b]in d ol-2-in iu m Iod id e (26).
After the solution was stirred for 24 h, the solid was recrystal-
lized from EtOH/EtOAc to give 294 mg (95%) of a cream-
colored powder: mp 240-241 °C (lit.48 mp 232 °C, i-PrOH/
EtOAc); IR (KBr) νmax 3368, 1651, 1612, 1499, 1454, 1348, 1206
1
cm-1; H NMR (DMSO-d6) δ 13.01 (bs, 1H, NH), 9.82 (s, 1H),
8.65 (d, 1H, J ) 7.0 Hz), 8.34 (d, 1H, J ) 7.9 Hz), 8.01 (d, 1H,
J ) 7.0 Hz), 7.78 (d, 1H, J ) 8.2 Hz), 7.69 (t, 1H, J ) 8.2 Hz,
J ) 7.3 Hz), 7.49 (t, 1H, J ) 7.3 Hz, J ) 7.9 Hz), 4.36 (s, 3H)
ppm; MS (EI) m/ z (rel int) 183 (M+, 2), 182 (18), 168 (100),
142 (37), 128 (35). Anal. Calcd for C12H11IN2: C, 46.47; H,
3.57; N, 9.03. Found: C, 46.39; H, 3.32; N, 9.12.
1-Meth yl-5H-ben zo[f]p yr id o[4,3-b]in d ole (22). A mix-
ture of 22 and 23 was chromatographed (CH2Cl2/acetone, 9.5:
0.5) to give 177 mg of the title compound: mp 294-295 °C
(CH3CN, brown prisms); IR (KBr) νmax 3429, 2927, 1644, 1593,
1482, 1415, 1263, 1227, 1184 cm-1; 1H NMR (DMSO-d6) δ 11.66
(bs, 1H, NH), 8.69 (s, 1H, H11), 8.34 (d, 1H, H3, J 3-4 ) 5.6 Hz),
8.16 (d, 1H, H10, J 10-9 ) 8.4 Hz), 8.02 (d, 1H, H7, J 7-8 ) 8.1
Hz), 7.93 (s, 1H, H6), 7.49 (t, 1H, H8, J 8-7 ) 8.1 Hz, J 8-9 ) 6.9
Hz), 7.41 (t, 1H, H9, J 9-10 ) 8.4 Hz, J 9-8 ) 6.9 Hz), 7.31 (d,
1H, H4, J 4-3 ) 5.6 Hz), 3.03 (s, 3H) ppm; MS (EI) m/ z (rel int)
232 (M+, 100), 204 (16). Anal. Calcd for C16H12N2: C, 82.73;
H, 5.21; N, 12.06. Found: C, 82.60; H, 5.34; N, 12.06.
3-Meth yl-5H-ben zo[f]p yr id o[4,3-b]in d ole (23). Elution
with CH2Cl2/acetone (7:3) afforded 192 mg of the title com-
pound: mp 308-309 °C (CH3CN, cream-colored powder); IR
(KBr) νmax 3401, 3043, 1618, 1477, 1446, 1236, 1158 cm-1; 1H
NMR (DMSO-d6) δ 11.51 (bs, 1H, NH), 9.26 (s, 1H, H1), 8.71
5-Met h yl-11H -in d olo[3,2-c]q u in olin -5-in iu m
Iod id e
(27a ). After the solution was stirred for 24 h, the cream-
colored solid was crystallized from MeOH affording 331 mg
(92%): mp 298-299 °C (lit.48 mp 297 °C, MeOH); IR (KBr)
νmax 3420, 3053, 1630, 1608, 1544, 1512, 1456, 1350, 1230,
1
1194, 1118 cm-1; H NMR (DMSO-d6) δ 13.95 (bs, 1H), 10.21
(s, 1H), 8.83 (d, 1H, J ) 8.2 Hz), 8.48 (d, 1H, J ) 8.4 Hz), 8.36
(d, 1H, J ) 8.1 Hz), 8.17 (t, 1H, J ) 8.4 Hz, J ) 7.3 Hz), 8.07
(t, 1H, J ) 8.2 Hz, J ) 7.3 Hz), 7.90 (d, 1H, J ) 8.4 Hz), 7.71
(t, 1H, J ) 8.4 Hz, J ) 7.0 Hz), 7.57 (t, 1H, J ) 8.1 Hz, J ) 7.0
Hz), 4.56 (s, 3H) ppm; MS (EI) m/ z (rel int) 232 (M+, 51), 218
(33), 127 (100). Anal. Calcd for C18H17IN2: C, 53.35; H, 3.64;
N, 7.78. Found: C, 53.62; H, 3.52; N, 7.90.
(51) Nantka-Namirski, P.; Zieleniak, J . Acta Polon. Pharm. 1977,
34, 449.
(52) Roussel, O.; Buu-Ho¨ı, N. P.; J acquignon, P. J . Chem. Soc. 1965,
5458.
5,8,9-Tr im eth yl-11H-in d olo[3,2-c]qu in olin -5-in iu m Io-
d id e (27c). After the solution was stirred for 48 h, the solid
obtained was recrystallized from MeOH affording 345 mg