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G. Zedda et al.
Arch. Pharm. Chem. Life Sci. 2012, 345, 195–202
General synthetic procedure for the synthesis of indole-1-
carbinols 2a–k
Methyl 1-(hydroxymethyl)-1H-indole-3-carboxylate 2f
White solid (m.p. 111–1138C). H NMR (300 MHz, CDCl3): d 7.96
1
(d, J ¼ 7.5 Hz, 1H), 7.62 (s, 1H), 7.38 (d, J ¼ 7.5 Hz, 1H), 7.20–7.14
(m, 2H), 5.43 (s, 2H), 3.73 (s, 3H) ppm. 13C NMR (300 MHz, DMSO):
d 169.81, 137.02, 126.65, 126.41, 123.00, 122.47, 121.43, 116.12,
109.67, 69.99, 52.84 ppm. EI-MS m/z (%): 205 (23), 175 (74), 161 (5),
144 (100), 116 (27), 89 (22). IR (KBr): 3270, 1750, 1650, 1260,
1160 cmꢂ1. Anal. Calcd for C11H11NO3: C 64.39, H 5.36, N 6.83.
Found: C 64.41, H 5.34, N 6.82.
A
mixture of indole
1
(8.54 mmol), paraformaldehyde
(10.25 mmol) and oxide (145.18 mmol) was stirred for the period
indicated (TLC) at 658C. After reaction, the crude mixture was
washed with acetone and filtered through celite. The concen-
trated filtrate was flash chromatographed (hexane/ethyl acetate
3:1, 5:1 or 1:3) on silica gel, obtaining the desired product.
(1H-Indol-1-yl)methanol 2a
1-(Hydroxymethyl)-1H-indole-3-carbonitrile 2g
Sticky oil. 1H NMR (300 MHz, CDCl3): 7.62 (d, J ¼ 7.8 Hz, 1H), 7.45
(d, J ¼ 7.8 Hz, 1 H), 7.25 (t, 1H), 7.16 (m, 2H), 6.53 (d, J ¼ 3.3, 1 H),
5.61 (d, J ¼ 4.8 Hz, 2 H) ppm. 13C NMR (300 MHz, CDCl3):
White solid (m. p. 105–1078C). 1H NMR (300 MHz, DMSO): d 8.45
(s, 1H), 7.84 (d, J ¼ 8.5 Hz, 1H), 7.75 (d, J ¼ 8.5 Hz, 1H), 7.50–7.38
(m, 2H), 6.93 (t, J ¼ 7.2 Hz, 1H), 5.72 (d, J ¼ 7.2 Hz, 2H) ppm.
13C NMR (300 MHz, DMSO): d 141.87, 139.93, 132.55, 128.72,
127.44, 123.88, 121.07, 117.29, 89.26, 74.81 ppm. EI-MS m/z (%):
172 (45), 142 (68), 116 (100). IR (KBr): 3300, 2860, 2250, 1600,
1480, 1260 cmꢂ1. Anal. Calcd for C10H8N2O: C 69.77, H 4.65,
N 16.28. Found: C 69.76, H 4.65, N 16.29.
d
135.93, 128.80, 125.89, 121.24, 119.00, 118.42, 110.12,
109.06, 68.70 ppm. EI-MS m/z (%): 147 (55), 130 (4), 117 (100),
103 (1), 90 (40), 89 (45). IR (neat): 3250, 2980, 1625, 1470,
1260 cmꢂ1. Anal. Calcd for C9H9NO: C 73.47, H 6.12 N 9.52.
Found: C 73.40, H 6.03, N 9.49.
(3-Methyl-1H-indol-1-yl)methanol 2b
(3-(2-Bromophenyl)-1H-indol-1-yl)methanol 2h
Sticky oil. 1H NMR (300 MHz, CDCl3): d 7.59 (d, J ¼ 7.5 Hz, 1H),
7.39 (d, J ¼ 7.5 Hz, 1H), 7.27 (t, 1 H), 7.19 (t, 1 H), 6.91 (s, 1H),
5.50 (s, 2H), 2.34 (s, 3H) ppm. 13C NMR (300 MHz, DMSO): d 135.83,
128.79, 125.96, 121.21, 118.84, 118.53, 110.12, 109.56, 68.35,
9.67 ppm. EI-MS m/z (%): 161 (77), 144 (8), 139 (100), 103 (10),
77 (12). IR (neat): 3300, 2860, 1600, 1480, 1260 cmꢂ1. Anal. Calcd
for C10H11NO: C 74.53, H 6.83, N 8.69. Found: C 74.49, H 6.82,
N 8.70.
Gummy. 1H NMR (300 MHz, DMSO): d 7.93 (d, J ¼ 8.2 Hz, 1H),
7.86 (s, 1H), 7.77 (d, J ¼ 8.2 Hz, 1H), 7.73 (d, J ¼ 7.8 Hz, 1H),
7.56 (t, J ¼ 7.8 Hz, 2H), 7.39–7.24 (m, 3H), 6.61 (t, J ¼ 7.2 Hz,
1H), 5.71 (d, J ¼ 7.2 Hz, 2H) ppm. 13C NMR (300 MHz, DMSO):
d 136.30, 134.95, 128.69, 127.43, 127.07, 126.11, 124.69, 122.61,
120.78, 120.13, 118.51, 109.68, 69.93 ppm. EI-MS m/z (%): 303
[Mþ2] (24), 301 (22), 271 (45), 194 (100), 116 (67), 77 (40).
IR (KBr): 3310, 1640, 1420, 1260, 1130 cmꢂ1. Anal. Calcd
for C15H12 BrNO: C 59.80, H 3.99, N 4.65. Found: C 59.77,
H 4.00, N 4.62.
(3-(2-Methoxyphenyl)-1H-indol-1-yl)methanol 2c
Gummy. 1H NMR (300 MHz, CDCl3): d 7.78 (d, J ¼ 7.8 Hz, 1H),
7.62 (d, J ¼ 7.8 Hz, 1H), 7.53 (d, J ¼ 8.1 Hz, 1H), 7.28 (m, 2H),
7.19 (t, 1H), 7.04 (q, 2H), 5.67 (s, 2H), 5.30 (s, 1H), 3.85 (s, 3H) ppm.
13C NMR (300 MHz, DMSO): d 156.33, 144.01, 135.66, 129.71,
128.13, 127.21, 123.70, 121.35, 120.60, 119.97, 119.76, 111.70,
110.60, 68.78, 54.36 ppm. EI-MS m/z (%): 253 (25), 223 (100), 208
(42), 180 (26), 152 (20), 130 (8). IR (KBr): 3410, 1650, 1420, 1260,
1130 cmꢂ1. Anal. Calcd for C16 H15NO2: C 75.89, H 6.38, N 5.53.
Found: C 75.90, H 6.33, N.5.52.
(3-Bromo-1H-indol-1-yl)methanol 2i
White solid (decomposes). EI-MS m/z (%): 227 [Mþ2] (100), 225 (98),
197 (25), 195 (23), 116 (50), 89 (20).
(3-Iodo-1H-indol-1-yl)methanol 2j
White solid (decomposes). EI-MS m/z (%): 273 (100), 243 (88), 116
(65), 89 (23).
(2-Methyl-1H-indol-1-yl)methanol 2k
1-(Hydroxymethyl)-1H-indole-3-carbaldehyde 2d
1
Sticky oil . H NMR (300 MHz, CDCl3): d 7.54 (d, J ¼ 8.4 Hz, 1H),
White solid (m.p. 101–1038C). 1H NMR (300 MHz, DMSO): d 10.06
(s, 1H), 8.47 (s, 1H), 8.21 (d, J ¼ 8.1 Hz, 1H), 7.79 (d, J ¼ 8.1 Hz,
1H), 7.47–7.36 (m, 2H), 6.92 (t, 1H), 5.73 (d, 2H) ppm. 13C NMR
(300 MHz, DMSO): d 190.22, 145.64, 141.71, 130.09, 128.77,
12786, 126.20, 122.65, 116.77, 74.90 ppm. EI-MS m/z (%): 175
(23), 147 (20), 146 (55), 116 (100). IR (KBr): 3350, 2980, 2850,
1725, 1660, 1280 cmꢂ1. Anal. Calcd for C10H9NO2: C 68.57,
H 5.14, N 8.00. Found: C 68.55, H 5.16, N 7.87.
7.33 (d, J ¼ 8.4 Hz, 1H), 7.21 (t, J ¼ 8.4 Hz, 1H), 7.13 (t, J ¼ 8.4 Hz,
1H), 6.81 (s, 1H), 5.38 (s, 2H), 2.28 (s, 3H) ppm. 13C NMR (300 MHz,
DMSO): d 141.59, 133.02, 130.96, 125.41, 124.48, 114.83, 105.56,
105.43, 64.95, 19.04 ppm. EI-MS m/z (%): 161 (50), 144 (16),
130 (100), 117 (5), 103 (20). IR (neat): 3310, 2840, 1610, 1480,
1260 cmꢂ1. Anal. Calcd for C10 H11NO: C 74.53, H 6.83, N 8.69.
Found: C 74.51, H 6.79, N 8.66.
Biological general methods
Cell line and culture
1-(1-(Hydroxymethyl)-1H-indol-3-yl)ethanone 2e
White solid (m.p. 128–1308C). H NMR (300 MHz, DMSO): d 8.51
1
(s, 1H), 8.32 (d, J ¼ 8.7 Hz, 1H), 7.75 (d, J ¼ 8.7 Hz, 1H), 7.37
(m, 2H), 6.84 (t, J ¼ 7.5 Hz, 1H), 5.70 (d, J ¼ 7.5 Hz, 2H), 2.57
(s, 3H) ppm. 13C NMR (300 MHz, DMSO): d 218.51, 136.42, 127.65,
126.58, 122.93, 122.27, 121.56, 116.20, 109.99, 69.61, 28.14 ppm.
EI-MS m/z (%): 189 (27), 174 (12), 146 (45), 116 (100). IR (KBr): 3400,
2850, 1715, 1660, 1420, 1300 cmꢂ1. Anal. Calcd for C11H11NO2:
C 69.84, H 5.82, N 7.41. Found: C 69.82, H 5.79, N 7.40.
Rat FaO cell line was supplied by Interlab Cell Line Collection
(Servizio Biotecnologie, IST, Genova, Italy). FaO cells were main-
tained in Dulbecco’s medium (DMEM plus Glutamax I,
Invitrogen S.r.l., Milano, Italy) supplemented with penicillin,
streptomycin and 10% heat-inactivated fetal calf-serum (FCS)
(Invitrogen) in a humidified atmosphere of 5% CO2/95% air, at
378C. Indole-3-carbinol (I3C) and compounds 2a, 2b, 2d and 2e
ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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