JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
959
2
.5. General procedures for the synthesis of compounds 5a–h
127.43 (d, J ¼ 10.1 Hz), 129.68, 131.44 (d, J ¼ 8.2 Hz), 134.72, 137.90,
1
1
1
44.69, 160.15 (d, J ¼ 244.8 Hz), 162.79, 165.45 (d, J ¼ 3.1 Hz),
To a solution of the corresponding intermediate 4a–h (0.05 mmol)
in toluene (5 mL) was added TsOH (10 mg, 0.05 mmol), and the
mixture was refluxed at 110 C for 6 h under the monitoring of
TLC. Then the reaction mixture was diluted with toluene, washed
ꢀ1
72.54; IR (KBr, cm ): 2952, 2924, 2854, 1689, 1628, 1592, 1556,
492, 1456, 1378, 1212, 1148, 1077, 968, 829; HRMS (ESI): m/z
ꢃ
[
M þ H]þ calcd. for C39
3
H51FN O: 596.4016; found 596.4023.
3 2 4
with saturated NaHCO and brine, dried over anhydrous Na SO
and concentrated in vacuo. The residue was purified by silica gel
column chromatography (petroleum ether-acetone 150:1 ꢁ 80:1,
v/v) to give compounds 5a–h.
0
N-[5 -chloro-ursa-12-en-(2,3)-quinoline-28-oyl]-5-methyl-
2
1
.5.4.
,3,4-oxadiazole (5d)
ꢃ
1
Yellow solid; Yield 73%; M.p. 313 ꢁ 315 C; H NMR (500 MHz,
CDCl ): d 0.51 (s, 3H), 0.83 (s, 3H), 0.96 (d, J ¼ 6.4 Hz, 3H), 1.00 (d,
3
J ¼ 6.4 Hz, 3H), 1.11 (m, 1H), 1.18 (s, 3H), 1.38 (s, 3H), 1.41 (s, 3H),
2
.5.1. N-2-[ursa-12-en-(2,3)-quinoline-28-oyl]-5-methyl-1,3,4-oxa-
1
.42 ꢁ 1.80 (m, 12H), 1.87 (dd, J ¼ 13.6, 4.8 Hz, 1H), 1.92 (m, 1H),
diazole (5a)
ꢃ
1
2.04 (dd, J ¼ 11.4, 2.6 Hz, 1H), 2.10 (dt, J ¼ 18.2, 5.2 Hz, 1H), 2.32
m, 1H), 2.48 (s, 3H), 2.49 (m, 1H), 2.55 (d, J ¼ 15.5 Hz, 1H), 2.93 (d,
J ¼ 15.5 Hz, 1H), 5.42 (s, 1H), 7.50 (dd, J ¼ 8.9, 2.0 Hz, 1H), 7.59 (s,
Yellow solid; Yield 68%; M.p. 324 ꢁ 326 C; H NMR (300 MHz,
(
CDCl ): d 0.51 (s, 3H), 0.84 (s, 3H), 0.96 (d, J ¼ 6.2 Hz, 3H), 1.00 (d,
3
J ¼ 6.2 Hz, 3H), 1.11 (m, 1H), 1.18 (s, 3H), 1.40 (s, 3H), 1.43 (s, 3H),
1
3
1
(
2
H), 7.65 (d, J ¼ 1.9 Hz, 1H), 7.91 (d, J ¼ 9.0 Hz, 1H);
125 MHz, CDCl ): d 15.32, 16.51, 17.29, 20.49, 21.27, 21.73, 22.83,
3.72, 23.88, 25.02, 25.39, 27.62, 30.84, 32.07, 32.53, 36.27, 39.05,
C NMR
1
.50 ꢁ 1.80 (m, 12H), 1.91 (m, 2H), 2.05 (m, 2H), 2.32 (m, 1H), 2.47
3
(
1
m, 1H), 2.48 (s, 3H), 2.56 (d, J ¼ 15.8 Hz, 1H), 2.94 (d, J ¼ 15.3 Hz,
H), 5.42 (s, 1H), 7.40 (t, J ¼ 7.2 Hz, 1H), 7.58 (t, J ¼ 7.5 Hz, 1H), 7.67
1
3
39.24, 39.69, 40.32, 41.87, 42.27, 45.60, 46.38, 54.08, 54.19, 125.26,
(
(
d, J ¼ 6.0 Hz, 1H), 7.68 (s, 1H), 7.99 (d, J ¼ 8.4 Hz, 1H); C NMR
125 MHz, CDCl ): d 15.32, 16.48, 17.29, 20.55, 21.28, 22.84, 23.68,
3.86, 24.88, 25.45, 27.56, 30.80, 32.08, 32.58, 36.31, 38.94, 39.02,
1
1
1
8
27.38, 127.69, 129.00, 129.79, 130.63, 131.18, 134.69, 139.20,
3
ꢀ
1
45.98, 162.85, 165.47, 172.56; IR (KBr, cm ): 2924, 2854, 1735,
2
3
1
1
1
671, 1624, 1592, 1554, 1492, 1457, 1379, 1221, 1080, 1030, 964,
9.23, 39.70, 40.41, 41.62, 42.23, 45.61, 46.45, 53.98, 54.16, 125.52,
26.66, 127.06, 127.42, 128.15, 128.77, 129.08, 135.33, 137.89,
47.59, 162.79, 166.15, 172.56; IR (KBr, cm ): 2954, 2924, 2853,
735, 1661, 1591, 1485, 1466, 1379, 1184, 1082, 966, 851, 748;
þ
05, 734; HRMS (ESI): m/z [M þ H] calcd. for C H ClN O:
3
9
51
3
ꢀ
1
612.3721; found 612.3726.
HRMS (ESI): m/z [M þ H]þ calcd. for C H N O: 578.4110;
3
9 52 3
2
.5.5. N-2-[ursa-12-en-(2,3)-quinoline-28-oyl]-5-butyl-1,3,4-oxadia-
found 578.4113.
zole (5e)
ꢃ
1
White solid; Yield 78%; M.p. 328 ꢁ 330 C; H NMR (500 MHz,
0
CDCl ): d 0.49 (s, 3H), 0.83 (s, 3H), 0.94 (t, J ¼ 7.8 Hz, 3H), 0.96 (d,
2
1
.5.2. N-[5 -methoxy-ursa-12-en-(2,3)-quinoline-28-oyl]-5-methyl-
,3,4-oxadiazole (5b)
3
J ¼ 6.9 Hz, 3H), 1.01 (d, J ¼ 6.4 Hz, 3H), 1.11 (m, 1H), 1.18 (s, 3H),
ꢃ
1
1.38 (m, 2H), 1.40 (s, 3H), 1.43 (s, 3H), 1.45 ꢁ 1.73 (m, 14H), 1.95
Yellow solid; Yield 73%; M.p. 313 ꢁ 315 C; H NMR (500 MHz,
(
1
2
m, 2H), 2.01 (dd, J ¼ 11.2, 2.2 Hz, 1H), 2.11 (dt, J ¼ 18.2, 5.2 Hz,
CDCl ): d 0.50 (s, 3H), 0.83 (s, 3H), 0.96 (d, J ¼ 6.4 Hz, 3H), 1.00 (d,
3
H), 2.32 (m, 1H), 2.47 (d, J ¼ 11.2 Hz, 1H), 2.56 (d, J ¼ 15.4 Hz, 1H),
.81 (m, 2H), 2.93 (d, J ¼ 15.4 Hz, 1H), 5.41 (s, 1H), 7.40 (t,
J ¼ 6.4 Hz, 3H), 1.14 (m, 1H), 1.17 (s, 3H), 1.36 (s, 3H), 1.40 (s, 3H),
1
(
1
(
.42 ꢁ 1.80 (m, 12H), 1.91 (m, 2H), 2.02 (m, 2H), 2.32 (m, 1H), 2.47
J ¼ 7.5 Hz, 1H), 7.57 (t, J ¼ 7.5 Hz, 1H), 7.66 (d, J ¼ 6.8 Hz, 1H), 7.67
m, 1H), 2.48 (s, 3H), 2.54 (d, J ¼ 15.1 Hz, 1H), 2.90 (d, J ¼ 15.5 Hz,
1
3
(
s, 1H), 7.99 (d, J ¼ 8.5 Hz, 1H); C NMR (125 MHz, CDCl
3
): d 13.85,
H), 3.90 (s, 3H, OCH ), 5.42 (s, 1H), 6.94 (d, J ¼ 2.6 Hz, 1H), 7.24
3
1
3
1
2
3
1
1
1
5.50, 16.43, 17.30, 20.52, 21.27, 22.83, 23.47, 23.84, 25.15, 25.44,
dd, J ¼ 9.2, 2.7 Hz, 1H), 7.57 (s, 1H), 7.88 (d, J ¼ 9.2 Hz, 1H);
C
8.01, 30.37, 30.75, 31.59, 32.07, 32.41, 36.31, 38.95, 39.12, 39.71,
9.85, 40.42, 41.74, 42.83, 45.70, 47.94, 53.26, 54.08, 125.57,
26.69, 127.07, 127.48, 128.17, 128.60, 128.99, 135.07, 137.87,
3
NMR (125 MHz, CDCl ): d 15.32, 16.51, 17.28, 20.49, 21.27, 21.73,
2
3
5
1
2.83, 23.72, 23.88, 25.02, 25.39, 27.62, 30.84, 32.07, 32.53, 36.27,
9.05, 39.24, 39.69, 40.32, 41.87, 42.27, 45.60, 46.38, 54.08, 54.19,
ꢀ
1
47.24, 162.81, 167.82, 172.51; IR (KBr, cm ): 2954, 2925, 2855,
739, 1583, 1552, 1492, 1456, 1378, 1189, 1081, 967, 753, 723;
5.61 (OCH ), 104.20, 119.31, 126.66, 127.83, 129.00, 130.56,
3
34.30, 137.87, 143.79, 157.23, 162.75, 163.44, 172.56; IR (KBr,
HRMS (ESI): m/z [M þ H]þ calcd. for C H N O: 620.4580;
ꢀ
1
cm ): 2924, 2854, 1735, 1671, 1624, 1592, 1554, 1492, 1457,
1
calcd. for C40
42 58 3
þ
379, 1221, 1080, 1030, 964, 805, 734; HRMS (ESI): m/z [M þ H]
found: 620.4572.
54 3 2
H N O : 608.4216; found 608.4219.
0
2.5.6.
N-[5 -methoxy-ursa-12-en-(2,3)-quinoline-28-oyl]-5-butyl-
0
2
1
.5.3.
N-[5 -fluoro-ursa-12-en-(2,3)-quinoline-28-oyl]-5-methyl- 1,3,4-oxadiazole (5f)
ꢃ
1
,3,4-oxadiazole (5c)
White solid; Yield 63%; M.p. 304 ꢁ 306 C; H NMR (500 MHz,
ꢃ
1
Yellow solid; Yield 70%; M.p. 318 ꢁ 320 C; H NMR (500 MHz, CDCl
): d 0.49 (s, 3H), 0.83 (s, 3H), 0.94 (t, J ¼ 7.2 Hz, 3H), 0.96 (d,
3
CDCl ): d 0.51 (s, 3H), 0.83 (s, 3H), 0.96 (d, J ¼ 6.4 Hz, 3H), 1.01 (d, J ¼ 7.0 Hz, 3H), 1.01 (d, J ¼ 6.4 Hz, 3H), 1.14 (m, 1H), 1.18 (s, 3H),
3
J ¼ 6.4 Hz, 3H), 1.11 (m, 1H), 1.18 (s, 3H), 1.38 (s, 3H), 1.41 (s, 3H), 1.27 (m, 2H), 1.37 (s, 3H), 1.41 (s, 3H), 1.46 ꢁ 1.80 (m, 14H), 1.94
1
.45 ꢁ 1.78 (m, 12H), 1.87 (dd, J ¼ 13.6, 4.8 Hz, 1H), 1.92 (d, (m, 2H), 2.01 (d, J ¼ 11.3 Hz, 1H), 2.10 (m, 1H), 2.33 (m, 1H), 2.47
J ¼ 10.6 Hz, 1H), 2.04 (dd, J ¼ 11.6, 2.7 Hz, 1H), 2.10 (dt, J ¼ 18.8, (d, J ¼ 12.0 Hz, 1H), 2.54 (d, J ¼ 15.6 Hz, 1H), 2.81 (m, 2H), 2.90 (d,
5
2
(
5
2
3
5
.2 Hz, 1H), 2.32 (dt, J ¼ 13.4, 4.6 Hz, 1H), 2.48 (s, 3H), 2.49 (m, 1H), J ¼ 15.8 Hz, 1H), 3.90 (s, 3H, OCH
.55 (d, J ¼ 15.5 Hz, 1H), 2.92 (d, J ¼ 15.6 Hz, 1H), 5.42 (s, 1H), 7.28 (d, J ¼ 8.7 Hz, 1H), 7.56 (s, 1H), 7.88 (d, J ¼ 8.3 Hz, 1H); C NMR
): d 13.88, 15.52, 16.42, 17.29, 20.50, 21.26, 22.78,
3
), 5.41 (s, 1H), 6.94 (s, 1H), 7.23
1
3
m, 1H), 7.34 (dt, J ¼ 8.8, 2.5 Hz, 1H), 7.62 (s, 1H), 7.97 (dd, J ¼ 9.0, (125 MHz, CDCl
3
1
3
.3 Hz, 1H); C NMR (125 MHz, CDCl ): d 15.34, 16.47, 17.28, 20.52, 23.46, 23.82, 25.13, 25.43, 28.00, 29.47, 30.89, 31.72, 32.39, 32.56,
3
1.28, 22.83, 23.66, 23.85, 24.87, 25.43, 27.55, 30.79, 32.11, 32.54, 36.29, 37.01, 39.10, 39.70, 39.85, 40.34, 42.81, 45.68, 46.39, 47.93,
6.29, 38.93, 39.01, 39.22, 39.70, 40.33, 41.61, 42.22, 45.58, 46.38, 53.24, 54.01, 55.72 (OCH
3.97, 54.09, 109.38 (d, J ¼ 19.5 Hz), 118.17 (d, J ¼ 17.1 Hz), 126.56, 130.56, 134.24, 137.89, 143.88, 157.36, 163.37, 165.27, 172.52; IR
), 104.37, 119.27, 126.75, 127.75, 128.90,
3