L. Huang et al. / Bioorg. Med. Chem. 20 (2012) 3038–3048
3045
the mixture was cooled to room temperature, filtered, and then
evaporated under vacuum. The crude product was chromato-
graphed on an Al2O3 column, eluted with CHCl3/MeOH as eluent
to afford the proposed compound.
142.69, 137.63, 137.47, 136.88, 133.00, 130.62, 128.75, 126.68,
126.34, 124.98, 123.40, 121.55, 121.00, 120.39, 120.21, 119.60,
119.18, 114.88, 111.04, 108.36, 105.39, 102.04, 97.30, 71.24,
64.44, 59.71, 57.01, 55.22, 29.43. HRMS m/z [M-Br]+ Calcd for
C36H30N2O5 571.2233, found 571.2249.
4.3.1. 9-O-2-(4-(2-Ethoxy)phenyl)benzofuran-berberine
bromide (26a)
4.3.5. 9-O-2-(4-(3-Ethoxy)phenyl)benzo[d]thiazole-berberine
bromide (28a)
Compound 21a was treated with berberrubine 25 according to
general procedure to give the desired product 26a as a yellow solid
(39% yield). Mp 216.3–218.3 °C; 1H NMR (400 MHz, DMSO) d 9.79
(s, 1H), 8.93 (s, 1H), 8.23 (d, J = 9.1 Hz, 1H), 8.03 (d, J = 9.1 Hz, 1H),
7.80 (d, J = 8.7 Hz, 2H), 7.76 (s, 1H), 7.61 (d, J = 7.1 Hz, 1H), 7.57 (d,
J = 7.8 Hz, 1H), 7.31–7.22 (m, 3H), 7.02 (s, 1H), 6.98 (d, J = 8.7 Hz,
2H), 6.14 (s, 2H), 4.83 (s, 2H), 4.71 (s, 2H), 4.53 (s, 2H), 4.08 (s,
3H), 3.13 (s, 2H). 13C NMR (101 MHz, DMSO) d 154.17, 150.94,
148.91, 148.05, 144.33, 141.99, 139.38, 138.14, 135.22, 133.07,
131.27, 128.46, 127.02, 126.47, 125.59, 125.98, 123.02, 121.94,
120.36, 120.11, 119.23, 119.09, 118.20, 113.54, 110.71, 109.13,
106.47, 100.13, 96.41, 74.29, 63.12, 57.88, 52.07. HRMS m/z [M-
Br]+ Calcd for C35H27NO6 558.1917, found 558.1929.
Compound 23a was treated with berberrubine 25 according to
general procedure to give the desired product 28a as a yellow solid
(35% yield). Mp 219.3–220.8 °C; 1H NMR (400 MHz, DMSO) d 9.79
(s, 1H), 8.92 (s, 1H), 8.23 (d, J = 9.2 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H),
8.04–7.94 (m, 4H), 7.74 (s, 1H), 7.52 (dd, J = 11.2, 4.1 Hz, 1H), 7.45–
7.41 (m, 1H), 7.09–6.98 (m, 3H), 6.13 (s, 2H), 4.89–4.80 (m, 2H),
4.73 (s, 2H), 4.57 (s, 2H), 4.11 (d, J = 21.9 Hz, 3H), 3.16–3.10 (m,
2H); 13C NMR (101 MHz, DMSO)
d 166.75, 160.52, 153.55,
150.21, 149.75, 147.60, 145.16, 142.40, 137.42, 134.17, 132.99,
130.44, 128.79, 126.62, 126.49, 125.65, 125.12, 123.62, 122.42,
122.12, 121.71, 120.27, 120.21, 115.23, 108.28, 105.32, 102.00,
72.08, 67.52, 57.02, 55.26, 30.63. HRMS m/z [M-Br]+ Calcd for
C34H26N2O5S 575.1641, found 575.1663.
4.3.2. 9-O-2-(4-(3-Propoxy)phenyl)benzofuran-berberine
bromide (26b)
4.3.6. 9-O-2-(4-(3-Opropoxy)phenyl)benzo[d]thiazole-berberine
bromide (28b)
Compound 21b was treated with berberrubine 25 according to
general procedure to give the desired product 26b as a yellow solid
(42% yield). Mp 210.3–213.0 °C; 1H NMR (400 MHz, DMSO) 9.82 (s,
1H), 8.57 (s, 1H), 8.30 (d, J = 9.1 Hz, 1H), 8.01 (d, J = 9.1 Hz, 1H),
7.80–7.67 (m, 3H), 7.50 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H),
7.17–7.01 (m, 4H), 6.90–6.81 (m, 1H), 6.75 (s, 1H), 6.16 (s, 2H),
4.91 (s, 2H), 4.49 (s, 2H), 4.37 (s, 2H), 4.07 (s, 3H), 3.22 (s, 2H),
2.41 (s, 2H). 13C NMR (101 MHz, DMSO) d 159.41, 153.66, 151.71,
149.37, 146.13, 144.50, 139.21, 138.86, 138.78, 134.10, 133.75,
126.79, 126.38, 125.21, 124.89, 124.10, 122.41, 121.57, 120.87,
120.01, 119.94, 118.32, 116.35, 110.59, 107.48, 105.29, 103.90,
96.09, 72.14, 65.37, 57.71, 56.91, 54.05, 28.62. HRMS m/z [M-Br]+
Calcd for C36H29NO6 572.2073, found 572.2094.
Compound 23b was treated with berberrubine 25 according to
general procedure to give the desired product 28b as a yellow solid
(25% yield). Mp 204.3–206.6 °C; 1H NMR (400 MHz, DMSO) d 9.82
(s, 1H), 8.93 (s, 1H), 8.19 (d, J = 9.1 Hz, 1H), 8.13–8.06 (m, 1H), 8.01
(dd, J = 15.0, 8.9 Hz, 4H), 7.77 (s, 1H), 7.52 (t, J = 7.3 Hz, 1H), 7.43 (t,
J = 7.2 Hz, 1H), 7.14 (d, J = 8.7 Hz, 2H), 7.06 (s, 1H), 6.15 (s, 2H), 4.92
(s, 2H), 4.52 (t, J = 6.0 Hz, 2H), 4.39 (t, J = 6.0 Hz, 2H), 4.02 (s, 3H),
3.20 (s, 2H), 2.42–2.36 (m, 2H); 13C NMR (101 MHz, DMSO) d
166.88, 161.04, 153.63, 150.23, 149.83, 147.67, 145.18, 142.73,
137.48, 134.19, 133.05, 130.54, 128.83, 126.71, 126.43, 125.59,
125.05, 123.38, 122.40, 122.08, 121.54, 120.35, 120.22, 115.21,
108.33, 105.38, 102.02, 71.14, 64.79, 57.02, 55.24, 29.36, 26.33.
HRMS m/z [M-Br]+ Calcd for C35H28N2O5S 589.1797, found
589.1826.
4.3.3. 9-O-2-(4-(3-Ethoxy)phenyl)-1H-indole-berberine bromide
(27a)
Compound 22a was treated with berberrubine 25 according to
general procedure to give the desired product 27a as a yellow solid
(30% yield). Mp 211.4–213.7 °C; 1H NMR (400 MHz, DMSO) d 11.36
(s, 1H), 9.79 (s, 1H), 8.93 (s, 1H), 8.23 (d, J = 9.2 Hz, 1H), 8.03 (d,
J = 9.1 Hz, 1H), 7.76 (d, J = 3.5 Hz, 2H), 7.74 (s, 1H), 7.48 (d,
J = 7.7 Hz, 1H), 7.36 (d, J = 7.9 Hz, 1H), 7.10–7.02 (m, 2H), 6.97 (t,
J = 8.0 Hz, 3H), 6.72 (d, J = 1.5 Hz, 1H), 6.07 (d, J = 59.8 Hz, 2H),
4.92–4.75 (m, 2H), 4.70 (dd, J = 5.3, 2.7 Hz, 2H), 4.60–4.44 (m,
2H), 4.19–3.96 (m, 3H), 3.17–3.06 (m, 2H); 13C NMR (101 MHz,
DMSO) d 157.47, 150.29, 149.79, 147.65, 145.21, 142.48, 137.48,
137.44, 136.87, 132.97, 130.47, 128.72, 126.62, 126.29, 125.15,
124.31, 123.61, 121.76, 121.06, 120.31, 120.23, 119.61, 119.20,
114.83, 111.01, 108.32, 105.37, 102.03, 97.42, 72.21, 67.12, 57.02,
54.85. HRMS m/z [M-Br]+ Calcd for C35H28N2O5 557.2100, found
557.2076.
4.3.7. 9-O-2-(4-(3-Ethoxy)phenyl)benzo[d]oxazole-berberine
bromide (29a)
Compound 24a was treated with berberrubine 25 according to
general procedure to give the desired product 29a as a yellow solid
(33% yield). Mp 221.4–224.1 °C; 1H NMR (400 MHz, DMSO) d 9.80
(s, 1H), 8.92 (s, 1H), 8.23 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 8.8 Hz, 2H),
8.03 (d, J = 9.1 Hz, 1H), 7.74 (td, J = 5.2, 1.7 Hz, 3H), 7.42–7.38 (m,
2H), 7.08 (d, J = 8.8 Hz, 2H), 7.02 (s, 1H), 6.13 (s, 2H), 4.88–4.79
(m, 2H), 4.73 (s, 2H), 4.58 (s, 2H), 4.07 (s, 3H), 3.17–3.19 (m, 2H);
13C NMR (101 MHz, DMSO) d 163.45, 163.01, 151.43, 151.09,
150.37, 146.21, 144.79, 141.97, 141.29, 138.62, 135.34, 132.77,
130.25, 129.07, 127.04, 125.33, 124.86, 122.42, 121.55, 121.10,
120.17, 117.46, 116.36, 111.11, 106.24, 104.98, 100.86, 78.88,
70.57, 67.75, 55.67, 54.12. HRMS m/z [M-Br]+ Calcd for
C34H26N2O6 559.1869, found 559.1883.
4.3.4. 9-O-2-(4-(3-Propoxy)phenyl)-1H-indole-berberine
bromide (27b)
4.3.8. 9-O-2-(4-(3-Propoxy)phenyl)benzo[d]oxazole-berberine
bromide (29b)
Compound 22b was treated with berberrubine 25 according to
general procedure to give the desired product 27b as a yellow solid
(38% yield). Mp 192.3–194.9 °C; 1H NMR (400 MHz, DMSO) d 11.44
(s, 1H), 9.81 (s, 1H), 8.94 (s, 1H), 8.20 (d, J = 9.1 Hz, 1H), 8.00 (d,
J = 9.1 Hz, 1H), 7.80 (d, J = 9.0 Hz, 3H), 7.49 (d, J = 7.7 Hz, 1H),
7.37 (d, J = 8.0 Hz, 1H), 7.04 (dd, J = 19.3, 14.0 Hz, 4H), 6.97 (t,
J = 7.4 Hz, 1H), 6.75 (s, 1H), 6.16 (s, 2H), 4.90 (s, 2H), 4.51 (s, 2H),
4.33 (s, 2H), 4.03 (s, 3H), 3.19 (s, 2H), 2.37 (s, 2H); 13C NMR
Compound 24b was treated with berberrubine 25 according to
general procedure to give the desired product 29b as a yellow solid
(42% yield). Mp 210.5–212.4 °C; 1H NMR (400 MHz, DMSO) d 9.81
(s, 1H), 8.92 (s, 1H), 8.19 (d, J = 9.2 Hz, 1H), 8.15 (d, J = 8.9 Hz, 2H),
8.00 (d, J = 9.1 Hz, 1H), 7.78–7.73 (m, 3H), 7.42–7.38 (m, 2H), 7.19
(d, J = 8.9 Hz, 2H), 7.07 (s, 1H), 6.16 (s, 2H), 4.94–4.88 (m, 2H), 4.51
(t, J = 6.2 Hz, 2H), 4.40 (t, J = 6.1 Hz, 2H), 4.02 (s, 3H), 3.22–3.17 (m,
2H), 2.42–2.36 (m, 2H); 13C NMR (101 MHz, DMSO) d 162.28,
161.44, 150.23, 150.06, 149.78, 147.64, 145.20, 142.67, 141.60,
(101 MHz, DMSO)
d 158.01, 150.28, 149.80, 147.65, 145.23,