12
P. Chen et al. / European Journal of Medicinal Chemistry 183 (2019) 111722
ꢁ
1 1
1
1
453, 1363, 1219, 1029 cm ; H NMR (400 MHz, CDCl
3
):
d
7.85 (s,
J ¼ 16.0 Hz,1H), 6.38 (dt, J ¼ 16.0, 6.2 Hz,1H), 4.74 (d, J ¼ 6.2 Hz, 2H),
4.10 (m, 2H), 2.96 (dd, J ¼ 18.6, 3.0 Hz, 1H), 2.19 (d, J ¼ 13.2 Hz, 1H),
1.99 (d, J ¼ 18.6 Hz, 1H), 1.90e1.58 (m, 7H), 1.49e1.39 (m, 4H), 1.28
(t, J ¼ 7.1 Hz, 3H), 1.25e1.21 (m, 1H), 1.19 (s, 3H), 1.14 (s, 3H),
H), 7.52 (d, J ¼ 8.3 Hz, 2H), 7.37 (d, J ¼ 8.3 Hz, 2H), 6.54 (d,
J ¼ 16.0 Hz,1H), 6.36 (dt, J ¼ 5.9,16.0 Hz, 1H), 4.67 (d, J ¼ 5.9 Hz, 2H),
.03 (m, 2H), 2.90 (dd, J ¼ 2.8, 18.6 Hz, 1H), 2.11 (d, J ¼ 13.2 Hz, 1H),
.92 (d, J ¼ 18.6 Hz, 1H), 1.50e1.82 (m, 7H), 1.31e1.41 (m, 4H),
4
1
1
3
CDCl
1
4
13
3
1.12e0.84 (m, 5H), 0.79 (s, 3H); C NMR (100 MHz, CDCl ): d 177.4,
.21e1.27 (m, 1H), 1.19 (t, J ¼ 7.2 Hz, 3H), 1.12e1.17 (m, 1H), 1.11 (s,
169.7, 154.7, 145.4, 132.8, 132.0, 127.7, 124.9, 123.0, 119.3, 111.4, 106.7,
74.3, 60.0, 57.2, 56.5, 55.0, 43.8, 43.7, 40.9, 40.7, 40.0, 39.6, 38.1, 38.0,
13
H),1.07 (s, 3H), 0.75e1.03 (m, 5H), 0.71 (s, 3H); C NMR (100 MHz,
): 177.2, 169.6, 151.3, 150.4, 137.2, 131.4, 127.1, 127.0 (2C),
26.7, 124.5 (2C), 121.5, 73.9, 59.9, 57.1, 56.4, 54.9, 43.8, 43.6, 40.9,
3
d
37.6, 28.9, 22.3, 21.7, 20.5, 19.0, 14.2, 13.4; HRMS (ESI, m/z) calcu-
þ
lated for C33
H
44NO
3
S [MþH] : 534.3042; found: 534.3036.
0.6, 39.9, 39.6, 38.0, 38.0, 37.6, 28.9, 22.3, 21.7, 20.4, 18.9, 14.1, 13.4;
HRMS (ESI, m/z) calculated for C34
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-4,9,11b-trimethyl-8-((((E)-
3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)allyl)oxy)imino)tetra-
decahydro-6a,9-methanocyclohepta[a]naphthalene-4-
þ
H
45
N
2
O
4
[MþH] : 545.3379;
found: 545.3365.
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-4,9,11b-trimethyl-8-((((E)-
-(4-(morpholinomethyl)phenyl)allyl)oxy)imino)tetradecahy-
carboxylate (6rn). Colourless oil (325.8 mg, 61%); IR (KBr): 3020,
ꢁ
1 1
3
2934, 2848, 1768, 1716, 1616, 1453, 1352, 1232, 1042 cm ; H NMR
(400 MHz, CDCl ):
dro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
6rj). Colourless oil (411.5 mg, 71%); IR (KBr): 3020, 2926, 2848,
3
d
7.75 (d, J ¼ 8.0 Hz, 1H), 7.46 (d, J ¼ 8.0 Hz, 1H),
(
1
d
7.42 (s, 1H), 6.62 (d, J ¼ 16.1 Hz, 1H), 6.47 (dt, J ¼ 5.5, 16.1 Hz, 1H),
5.23 (s, 2H), 4.66 (d, J ¼ 5.5 Hz, 2H), 4.01 (m, 2H), 2.88 (dd, J ¼ 2.4,
18.5 Hz, 1H), 2.09 (d, J ¼ 13.2 Hz, 1H), 1.89 (d, J ¼ 18.5 Hz, 1H),
1.49e1.83 (m, 7H), 1.30e1.42 (m, 4H), 1.19 (t, J ¼ 7.1 Hz, 3H),
1.12e1.16 (m, 1H), 1.10 (s, 3H), 1.04 (s, 3H), 0.75e1.03 (m, 5H), 0.70
ꢁ1 1
719, 1608, 1454, 1362, 1218, 1030 cm ; H NMR (400 MHz, CDCl
3
):
7.36 (d, J ¼ 8.0 Hz, 2H), 7.29 (d, J ¼ 8.0 Hz, 2H), 6.60 (d, J ¼ 15.9 Hz,
H), 6.37 (dt, J ¼ 6.0, 15.9 Hz, 1H), 4.70 (d, J ¼ 6.0 Hz, 2H), 4.10 (m,
H), 3.71 (t, J ¼ 4.6 Hz, 4H), 3.49 (s, 2H), 2.94 (dd, J ¼ 2.9, 18.6 Hz,
H), 2.45 (t, J ¼ 4.6 Hz, 4H), 2.18 (d, J ¼ 13.2 Hz, 1H), 1.96 (d,
1
2
1
13
3
(s, 3H); C NMR (100 MHz, CDCl ): d 177.2, 170.7, 169.9, 147.2, 143.0,
J ¼ 18.6 Hz, 1H), 1.57e1.90 (m, 7H), 1.39e1.48 (m, 4H), 1.27 (t,
J ¼ 7.1 Hz, 3H), 1.20e1.24 (m, 1H), 1.18 (s, 3H), 1.12 (s, 3H), 0.84e1.08
130.6, 130.4, 127.4, 125.7, 124.5, 119.6, 73.4, 69.4, 59.9, 57.1, 56.4,
54.8, 43.8, 43.6, 40.9, 40.6, 39.9, 39.5, 38.0, 37.9, 37.5, 28.9, 22.2,
(
m, 5H), 0.77 (s, 3H); 13C NMR (100 MHz, CDCl
3
):
d
177.4, 169.7,
21.6, 20.4, 18.9, 14.1, 13.4; HRMS (ESI, m/z) calculated for C33
H
44NO
5
þ
1
6
3
37.1, 136.0, 132.1, 129.4 (2C), 126.4 (2C), 125.9, 74.1, 67.0 (2C), 63.1,
0.0, 57.2, 56.5, 55.0, 53.6 (2C), 43.8, 43.7, 41.0, 40.7, 40.0, 39.6, 38.1,
[MþH] : 534.3219; found: 534.3228.
Ethyl
(4R,4aS,6aR,9S,11aR,11bS,E)-8-((((E)-3-(dibenzo[b,d]
8.0, 37.6, 28.9, 22.3, 21.7, 20.5, 19.0, 14.2, 13.4; HRMS (ESI, m/z)
furan-2-yl)allyl)oxy)imino)-4,9,11b-trimethyltetradecahydro-
þ
calculated for C36
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-((((E)-3-(1H-indol-5-yl)
allyl)oxy)imino)-4,9,11b-trimethyltetradecahydro-6a,9-
53
H N
2
O
4
[MþH] : 577.4005; found: 577.4014.
6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
(6ro).
ꢀ
Colourless crystal (352.3 mg, 62%), m.p. 150.6e152.1 C; X-ray
crystal file is available from the Cambridge Crystallographic Data
Centre: CCDC 1554566; IR (KBr): 3020, 2924, 2848, 1720, 1452,
methanocyclohepta[a]naphthalene-4-carboxylate (6rk). Pale
yellow powder (352.1 mg, 68%); IR (KBr): 3363, 3020, 2933, 2848,
ꢁ1 1
3
1373, 1233, 1023 cm ; H NMR (400 MHz, CDCl ): d 7.91e8.03 (m,
ꢁ
1 1
1
718, 1612, 1454, 1365, 1231, 1027 cm ; H NMR (400 MHz, CDCl
3
):
2H), 7.33e7.62 (m, 5H), 6.79 (d, J ¼ 15.9 Hz, 1H), 6.45 (dt, J ¼ 6.2,
15.9 Hz, 1H), 4.77 (d, J ¼ 6.2 Hz, 2H), 4.11 (m, 2H), 2.98 (dd, J ¼ 3.0,
18.6 Hz, 1H), 2.19 (d, J ¼ 13.1 Hz, 1H), 2.01 (d, J ¼ 18.7 Hz, 1H),
1.67e1.88 (m, 7H),1.43e1.49 (m, 4H),1.27e1.29 (m, 4H),1.19 (s, 3H),
d
7.65 (s, 1H), 7.32e7.34 (m, 2H), 7.16e7.19 (m, 1H), 6.76 (d,
J ¼ 15.8 Hz, 1H), 6.52e6.55 (m, 1H), 6.36 (dt, J ¼ 6.4, 15.8 Hz, 1H),
4
2
1
3
.76 (d, J ¼ 6.4 Hz, 2H), 4.12 (m, 2H), 2.99 (dd, J ¼ 3.0, 18.6 Hz, 1H),
.20 (d, J ¼ 13.2 Hz, 1H), 2.02 (d, J ¼ 18.6 Hz, 1H), 1.59e1.91 (m, 7H),
13
1.15 (s, 3H), 0.95e1.10 (m, 5H), 0.80 (s, 3H); C NMR (100 MHz,
CDCl ): 177.4, 169.8, 156.6, 155.9, 132.5, 132.1, 127.3, 125.9, 125.3,
.40e1.50 (m, 4H), 1.28 (t, J ¼ 7.1 Hz, 3H), 1.22e1.25 (m, 1H), 1.21 (s,
3
d
13
H), 1.16 (s, 3H), 0.84e1.13 (m, 5H), 0.80 (s, 3H); C NMR (100 MHz,
): 177.6, 169.7, 135.7, 134.2, 128.9, 128.1, 124.8, 122.9, 120.6,
124.5, 124.1, 122.8, 120.7, 118.5, 111.7, 111.6, 74.3, 60.0, 57.2, 56.5,
55.0, 43.8, 43.7, 41.0, 40.7, 40.0, 39.6, 38.1, 38.0, 37.7, 28.9, 22.3, 21.7,
CDCl
3
d
1
4
19.4, 111.2, 102.8, 74.7, 60.1, 57.2, 56.5, 55.1, 43.8, 43.7, 41.0, 40.7,
20.5, 19.0, 14.2, 13.5; HRMS (ESI, m/z) calculated for C37
H
46NO
4
þ
0.0, 39.6, 38.1 (2C), 37.7, 29.0, 22.4, 21.7, 20.5,19.0,14.2,13.4; HRMS
[MþH] : 568.3427; found: 568.3432.
þ
(
5
ESI, m/z) calculated for C33
17.3441.
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-((((E)-3-(benzofuran-5-
H
45
N
2
O
3
[MþH] : 517.3430; found:
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-((((E)-3-(9H-carbazol-3-
yl)allyl)oxy)imino)-4,9,11b-trimethyltetradecahydro-6a,9-
methanocyclohepta[a]naphthalene-4-carboxylate (6rp). Pale
yellow powder (347.2 mg, 61%); IR (KBr): 3394, 2927, 2847, 1716,
yl)allyl)oxy)imino)-4,9,11b-trimethyltetradecahydro-6a,9-
methanocyclohepta[a]naphthalene-4-carboxylate (6rl). White
powder (332.1 mg, 64%); IR (KBr): 3020, 2927, 2848, 1719, 1609,
ꢁ
1 1
1602, 1465, 1326, 1233, 1147, 1027, 753 cm
; H NMR (400 MHz,
CDCl ): 8.4 (s, 1H), 8.1e8.06 (m, 2H), 7.53e7.23 (m, 5H), 6.82 (d,
3
d
ꢁ1
1
1467, 1364, 1234, 1030 cm
;
H
NMR (400 MHz, CDCl
3
):
J ¼ 15.8 Hz, 1H), 6.44 (dt, J ¼ 15.8, 6.3 Hz), 4.82 (d, J ¼ 6.3 Hz), 4.12
(m, 2H), 3.03 (dd, J ¼ 18.6, 2.6 Hz, 1H), 2.21 (d, J ¼ 13.2 Hz, 1H), 2.06
(d, J ¼ 18.6, 1H), 1.94e1.60 (m, 7H), 1.54e1.40 (m, 4H), 1.28 (t,
J ¼ 7.1 Hz, 3H), 1.26e1.23 (m, 1H), 1.22 (s, 3H), 1.19 (s, 3H), 1.15e0.84
d
7.59e7.63 (m, 2H), 7.37e7.47 (m, 2H), 6.75e6.76 (m, 1H), 6.72 (d,
J ¼ 16.1 Hz, 1H), 6.37 (dt, J ¼ 6.2, 16.1 Hz, 1H), 4.74 (d, J ¼ 6.2 Hz, 2H),
.10 (m, 2H), 2.96 (dd, J ¼ 3.0, 18.6 Hz, 1H), 2.18 (d, J ¼ 13.2 Hz, 1H),
.99 (d, J ¼ 18.6 Hz, 1H), 1.59e1.88 (m, 7H), 1.39e1.49 (m, 4H), 1.27
4
1
13
3
(m, 5H), 0.82 (s, 3H); C NMR (100 MHz, CDCl ): d 177.6, 170.0,
(
0
t, J ¼ 7.1 Hz, 3H), 1.20e1.24 (m, 1H), 1.19 (s, 3H), 1.14 (s, 3H),
140.0, 139.3, 133.9, 128.5, 125.9, 124.6, 123.5, 123.3, 123.1, 120.4,
119.5, 118.7, 110.8, 110.7, 74.7, 60.1, 57.2, 56.5, 55.0, 43.9, 43.8, 41.0,
13
3
.83e1.11 (m, 5H), 0.79 (s, 3H); C NMR (100 MHz, CDCl ): d 177.4,
1
69.7, 154.7, 145.4, 132.8, 132.0, 127.7, 124.9,123.0, 119.3, 111.4, 106.7,
40.7, 40.0, 39.6, 38.1, 38.0, 37.8, 29.0, 22.4, 21.8, 20.5, 19.0, 14.2, 13.5;
þ
74.3, 60.0, 57.2, 56.5, 55.0, 43.8, 43.7, 41.0, 40.7, 40.0, 39.6, 38.1, 38.0,
HRMS (ESI, m/z) calculated for C37
found: 567.3583.
H
47
N
2
O
3
[MþH] : 567.3587;
37.6, 28.9, 22.3, 21.7, 20.5, 19.0, 14.2, 13.4; HRMS (ESI, m/z) calcu-
þ
lated for C33
H44NO
4
[MþH] : 518.3270; found: 518.3279.
Methyl
4-((E)-3-((((4R,4aS,6aR,9S,11aR,11bS,E)-4-(ethox-
Ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-((((E)-3-(benzo[b]thio-
phen-5-yl)allyl)oxy)imino)-4,9,11b-trimethyltetradecahydro-
ycarbonyl)-4,9,11b-trimethyldodecahydro-6a,9-
methanocyclohepta[a]naphthalen-8(7H)-ylidene)amino)oxy)
prop-1-en-1-yl)-1H-pyrrole-2-carboxylate (6rq). Colourless oil
(118.5 mg, 23%); IR (KBr): 3411, 3119, 2961, 2927, 2855, 1719, 1666,
6
a,9-methanocyclohepta[a]naphthalene-4-carboxylate (6rm).
Pale yellow powder (66%); IR (KBr): 3043, 2927, 2848, 1719, 1655,
ꢁ
1
1
ꢁ1 1
1452, 1363, 1230, 1152, 1029, 900 cm ; H NMR (400 MHz, CDCl
3
):
1457, 1373, 1261, 1021 cm ; H NMR (400 MHz, CDCl
3
): d 6.89e7.05
d
7.63e7.60 (m, 2H), 7.48e7.37 (m, 2H), 6.77e6.75 (m, 1H), 7.3 (d,
(m, 2H), 6.49 (d, J ¼ 15.8 Hz, 1H), 6.13 (dt, J ¼ 6.2, 15.8 Hz, 1H), 4.64