J. Zheng et al. / European Journal of Medicinal Chemistry 65 (2013) 158e167
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99.90, 54.48, 25.50; ESIeMS (m/z): 305.3 [M þ H]þ; HRMS (m/z):
calcd for C20H17N2F þ H: 305.14485, found: 305.14491.
154.90, 147.95, 137.75, 129.42, 128.46, 127.98, 125.88, 125.79, 122.71,
122.25, 120.61, 120.44, 118.81, 118.73, 113.72, 101.15, 52.90, 49.53,
24.68; ESIeMS (m/z): 312.3 [M þ H]þ; HRMS (m/z): calcd for C21H18
N3 þ H: 312.1495, found: 312.14998.
5.2.2.6. (E)-2-(2-(5-methyl-1H-indole-3-yl)vinyl)-3,3-dimethyl-3H-
indole (5f). Orange red oil, Rf ¼ 0.52, yield 98.0%; 1H NMR
(300 MHz, CD3OD)
d
: 7.98 (d, J ¼ 16.4 Hz, 1H), 7.78 (s, 0H), 7.61 (s,
5.2.3. Syntheses of simplified vinca alkaloids (7aep)
1H), 7.48 (d, J ¼ 7.6 Hz, 1H), 7.33 (d, J ¼ 8.3 Hz, 1H), 7.27e7.21 (m,
1H), 7.18 (s, 1H), 7.10 (d, J ¼ 16.4 Hz, 1H), 7.10 (m, 1H), 7.01 (d,
J ¼ 8.4 Hz, 1H), 2.45 (s, 3H), 1.40 (s, 6H); 13C NMR (75 MHz, CD3OD)
General procedure: The procedure was the same as described in
Section 5.2.2. Only replace substituted indole-3-carbaldehydes
(4aek) with substituted benzaldehydes (6aep) as reactants. The
resulted residue was further purified by flash column chromatog-
raphy using ethyl acetate/petroleum ether (1:3, v/v) or otherwise
marked ratio as the eluent to give pure products (7aep).
d: 187.40, 154.89, 148.18, 138.25, 136.53, 132.14, 131.51, 129.56,
127.69, 126.98, 126.21, 123.12, 121.57, 120.61, 115.70, 115.38, 113.68,
54.12, 25.68, 22.82; ESIeMS (m/z): 301.3 [M þ H]þ; HRMS (m/z):
calcd for C21H21N2 þ H: 301.16993, found: 301.16995.
5.2.3.1. (E)-2-(4-N,N-dimethylaminostyryl)-3,3-dimethyl-3H-indole
5.2.2.7. (E)-2-(2-(5-bromo-1H-indole-3-yl)vinyl)-3,3-dimethyl-3H-
(7a). Red brown solid, Rf ¼ 0.71 (ethyl acetate/petroleum ether
indole (5g). Orange red oil, Rf ¼ 0.51, yield 87.2%; 1H NMR
(1:1, v/v)), yield 78.4%; 1H NMR (300 MHz, CD3OD)
d: 7.68 (d,
(300 MHz, CDCl3)
d
: 8.09 (s, 1H), 7.97 (d, J ¼ 16.4 Hz, 1H), 7.64 (d,
J ¼ 16.3 Hz, 1H), 7.58e7.52 (m, 2H), 7.49 (d, J ¼ 7.5 Hz, 1H), 7.40e
7.36 (m, 1H), 7.33 (t, J ¼ 7.6, 1.3 Hz, 1H), 7.22 (t, J ¼ 7.4, 1.1 Hz, 1H),
6.93 (d, J ¼ 16.3 Hz, 1H), 6.79e6.73 (m, 2H), 3.03 (d, J ¼ 9.5 Hz, 6H,
J ¼ 7.6 Hz, 1H), 7.48 (s, 2H), 7.38 (d, J ¼ 7.7 Hz, 1H), 7.35 (s, 1H), 7.29e
7.19 (m, 2H), 7.04 (d, J ¼ 16.4 Hz, 1H), 1.55 (s, 6H, eCH3); 13C NMR
(75 MHz, CDCl3)
d
184.82, 153.66, 146.40, 136.12, 132.07, 128.90,
eCH3), 1.47 (s, 6H, eCH3). 13C NMR (75 MHz, CD3OD)
d: 187.11,
127.93, 127.18, 125.91, 125.29, 122.81, 121.36, 119.68, 115.42, 114.47,
114.19, 113.59, 52.59, 24.30; ESIeMS (m/z): 365.2 [M þ H]þ; HRMS
(m/z): calcd for C20H17BrN2 þ H: 365.06479, found: 365.06418.
155.08, 154.01, 148.50, 142.37, 131.22, 129.71, 127.36, 125.81, 123.32,
121.00, 115.61, 114.07, 54.51, 41.19, 25.38; ESIeMS (m/z): 291.3
[M þ H]þ; HRMS (m/z): calcd for C20H22N2 þ H: 291.18558, found:
291.18563.
5.2.2.8. (E)-2-(2-(1,2-dimethyl-1H-indole-3-yl)vinyl)-3,3-dimethyl-
3H-indole (5h). Orange red oil, Rf ¼ 0.55, yield 87.1%; 1H NMR
5.2.3.2. (E)-2-(4-methoxystyryl)-3,3-dimethyl-3H-indole
(7b).
(300 MHz, CDCl3)
d
: 8.17 (d, J ¼ 16.1 Hz, 1H), 8.08 (d, J ¼ 7.2 Hz, 1H),
Green solid powder, Rf ¼ 0.56, yield 57.2%; 1H NMR (300 MHz,
7.69 (d, J ¼ 7.6 Hz, 1H), 7.38 (dd, J ¼ 7.5, 1.1 Hz, 1H), 7.35e7.32 (m,
1H), 7.30 (dd, J ¼ 7.7, 1.6 Hz, 1H), 7.27e7.23 (m, 1H), 7.21 (dd, J ¼ 7.5,
1.9 Hz, 2H), 7.07 (d, J ¼ 16.1 Hz,1H), 3.54 (s, 3H, eCH3), 2.45 (s, 3H, e
CDCl3)
d
: 7.71 (d, J ¼ 16.4 Hz, 1H), 7.64 (d, J ¼ 7.6 Hz, 1H), 7.57 (m,
2H), 7.37e7.32 (m, 1H), 7.29 (t, 1H), 7.22 (t, 1H), 6.99 (s, 1H), 6.96
(d, J ¼ 16.4 Hz, 1H), 6.92(d, J ¼ 7.2, 1H), 3.82 (s, 3H, eOCH3), 1.46 (s,
CH3), 1.53 (s, 6H, eCH3); 13C NMR (75 MHz, CDCl3)
d: 185.19, 154.08,
6H, eCH3); 13C NMR (75 MHz, CDCl3)
d: 183.63, 160.75, 153.84,
146.04, 141.41, 137.68, 132.61, 127.85, 125.58, 124.75, 122.13, 121.25,
120.01, 119.50, 113.04, 110.32, 109.53, 49.86, 29.65, 24.38, 10.61;
146.48, 137.87, 129.06, 128.79, 127.82, 125.47, 121.12, 120.34, 117.48,
114.39, 55.34, 52.60, 23.95; ESIeMS (m/z): 278.3 [M þ H]þ; HRMS
(m/z): calcd for C19H19NO þ H: 278.15394, found: 278.15391.
ESIeMS (m/z): 315.3 [M
þ
H]þ; HRMS (m/z): calcd for
C
22H23N2 þ H: 315.18558, found: 315.18591.
5.2.3.3. (E)-2-(4-methylstyryl)-3,3-dimethyl-3H-indole
(7c). Green
5.2.2.9. (E)-2-(2-(7-nitro-1H-indole-3-yl)vinyl)-3,3-dimethyl-3H-
solid powder, Rf ¼ 0.54, yield 48.1%; 1H NMR (300 MHz, CDCl3)
d: 7.75
indole (5i). Orange solid powder, Rf ¼ 0.71, yield 85.5%; 1H NMR
(d, J ¼ 16.4 Hz,1H), 7.67 (d, J ¼ 7.6 Hz,1H), 7.54 (d, J ¼ 8.1 Hz,1H), 7.40e
7.35 (m, 1H), 7.35e7.31 (m, 1H), 7.29e7.25 (m, 1H), 7.23 (m, 2H), 7.07
(d, J ¼ 16.4 Hz, 1H), 2.40 (s, 3H, eCH3), 1.49 (s, 6H, eCH3); 13C NMR
(300 MHz, DMSO-d6)
d: 12.57 (s, 1H), 8.51 (s, 1H), 8.07 (d,
J ¼ 16.5 Hz, 1H), 7.94 (dd, J ¼ 3.5, 2.9 Hz, 1H), 7.93 (s, 1H), 7.54 (d,
J ¼ 7.5 Hz, 1H), 7.47 (d, J ¼ 6.8 Hz, 1H), 7.38 (t, J ¼ 7.7 Hz, 1H), 7.35 (s,
1H), 7.21 (d, J ¼ 7.4, 0.9 Hz, 1H), 7.03 (d, J ¼ 16.5 Hz, 1H), 1.47 (s, 6H,
(75 MHz, CDCl3) d: 183.49, 153.93, 146.56, 139.65, 138.07, 133.34,
129.66, 127.84, 127.50, 125.57, 121.12, 120.56, 118.85, 52.68, 23.91,
eCH3); 13C NMR (75 MHz, DMSO-d6)
d: 184.41, 154.94, 147.78,
21.46; ESIeMS (m/z): 262.3 [M þ H]þ; HRMS (m/z): calcd for
143.17, 140.22, 132.84, 131.23, 128.47, 125.79, 122.27, 121.92, 120.58,
119.87, 119.16, 118.10, 113.26, 52.93, 24.62; ESIeMS (m/z): 332
[M þ H]þ; HRMS (m/z): calcd for C20H18N3O2 þ H: 332.13935,
found:332.13997.
C19H20NO þ H: 262.15903, found: 262.15963.
5.2.3.4. (E)-2-(4-nitrostyryl)-3,3-dimethyl-3H-indole
(7d). Orange
: 8.29 (m,
1
solid, Rf ¼ 0.54, yield 22.6%; H NMR (300 MHz, CD3OD)
d
2H), 7.95 (d, J ¼ 8.7 Hz, 2H), 7.82 (d, J ¼ 16.5 Hz, 1H), 7.60 (d, J ¼ 7.2 Hz,
1H), 7.46 (d, J ¼ 7.3 Hz, 1H), 7.39 (d, J ¼ 16.5 Hz, 1H), 7.37 (m, 1H), 7.32
5.2.2.10. (E)-2-(2-(6-chloro-1H-indole-3-yl)vinyl)-3,3-dimethyl-3H-
indole (5j). Orange solid powder, Rf ¼ 0.65, yield 84.8%; 1H NMR
(d, J ¼ 7.4, 1.0 Hz, 1H), 1.52 (s, 6H, eCH3). 13C NMR (75 MHz, CD3OD)
d:
(300 MHz, CDCl3)
d
: 11.58 (s, 1H), 8.07 (m, 1H), 7.95 (d, J ¼ 16.3, 1H),
185.78, 154.77, 150.20, 148.92, 144.43, 138.35, 130.39, 129.97, 128.68,
125.97, 125.40, 123.54, 122.25, 55.04, 24.64. MW: 292, ESIeMS (m/z):
293.3 [M þ H]þ. HRMS (m/s): calcd for C18H16N2O2: 293.12845, found:
293.12845.
7.72 (s, 1H), 7.54 (dd, J ¼ 7.2, 4.7 Hz, 3H), 7.35 (m, 2H), 7.27e7.15 (m,
2H), 7.03 (d, J ¼ 16.3 Hz, 1H), 1.52 (s, 6H, eCH3); 13C NMR (75 MHz,
CDCl3)
d: 183.06, 153.09, 145.33, 137.01, 130.75, 128.57, 126.71,
126.52, 123.73, 122.84, 120.11, 119.91, 118.49, 113.88, 112.80, 111.10,
51.16, 22.94; ESIeMS (m/z): 321.2 [M þ H]þ; HRMS (m/z): calcd for
5.2.3.5. (E)-2-(3-methoxystyryl)-3,3-dimethyl-3H-indole
(7e).
C
20H18ClN2 þ H: 321.11530, found: 321.11516.
Light yellow oil, Rf ¼ 0.63, yield 42.5%; 1H NMR (300 MHz, CDCl3)
d
: 7.70 (d, J ¼ 16.4, 1H), 7.66 (m, 2H), 7.40e7.33 (m, 2H), 7.32 (d,
5.2.2.11. (E)-2-(2-(4-carbonitrile-1H-indole-3-yl)vinyl)-3,3-
J ¼ 5.9 Hz, 1H), 7.27 (d, J ¼ 7.6 Hz, 1H), 7.22 (d, J ¼ 7.5 Hz, 1H), 7.16
(s, 1H), 7.11 (d, J ¼ 16.4 Hz, 1H), 6.93 (dd, J ¼ 8.1, 2.3 Hz, 1H), 3.87 (s,
dimethyl-3H-indole (5k). Light yellow solid powder, Rf ¼ 0.72, yield
88.1%; 1H NMR (300 MHz, DMSO-d6)
d: 12.38 (s, 1H), 8.49 (d,
3H, eOCH3), 1.49 (s, 6H, eCH3); 13C NMR (75 MHz, CDCl3)
d:
J ¼ 1.9 Hz, 1H), 8.35 (d, J ¼ 16.5 Hz, 1H), 7.86 (d, J ¼ 8.1 Hz, 1H), 7.69
(d, J ¼ 7.3 Hz, 1H), 7.52 (t, 1H), 7.48 (d, J ¼ 7.1 Hz, 1H), 7.37 (d,
J ¼ 7.7 Hz, 1H), 7.32 (d, J ¼ 6.4 Hz, 1H), 7.26 (d, J ¼ 16.5 Hz, 1H), 7.21
183.26, 159.97, 153.66, 146.59, 138.05, 137.45, 129.88, 127.87,
125.79, 121.13, 120.64, 120.25, 115.25, 112.43, 55.32, 52.70, 23.89;
ESIeMS (m/z): 278.3 [M
þ
H]þ; HRMS (m/z): calcd for
(m, 1H), 1.52 (s, 6H, eCH3); 13C NMR (75 MHz, DMSO)
d
184.26,
C
19H19NO þ H: 278.15394, found: 278.15355.