Medicinal Chemistry Research
2.26 (dd, J = 13.2, 1.8 Hz, 1 H), 2.17–2.16 (m, 1 H), 2.14
(d, J = 2.6 Hz, 1 H), 2.12 (s, 3 H), 2.08 (d, J = 4.2 Hz, 1 H),
1.98 (dd, J = 12.2, 5.1 Hz, 1 H), 1.96–1.90 (m, 1 H),
1.77–1.71 (m, 1 H), 1.64 (dd, J = 12.8, 5.0 Hz, 1 H), 1.59
(d, J = 5.2 Hz, 1 H). 13C-NMR (100 MHz, CDCl3): δ 171.1,
154.2, 144.4, 138.1, 135.0, 134.7, 131.8 (×2), 130.4 (×2),
129.0, 127.5, 122.5, 119.7, 103.3, 80.5, 65.8, 54.6, 53.5,
52.1, 48.9, 39.3, 34.0, 22.0, 19.9. HRMS (ESI) m/z calcd
for C25H25BrO3Na [M + Na]+: 475.0879, 477.0862, found:
475.0868, 477.0853 (1:1).
5.22 (d, J = 4.0 Hz, 2 H), 4.98 (t, J = 2.5 Hz, 1 H), 4.72 (t,
J = 2.0 Hz, 1 H), 4.03 (s, 1 H), 3.82 (s, 3 H), 2.83 (dd, J =
12.5, 5.0 Hz, 1 H), 2.29–2.24 (m, 1 H), 2.22 (dd, J = 5.0,
1.7 Hz, 1 H), 2.18 (d, J = 2.7 Hz, 1 H), 2.15 (s, 3 H), 2.12
(d, J = 2.6 Hz, 1 H), 1.97 (dd, J = 12.2, 5.1 Hz, 1 H),
1.96–1.88 (m, 1 H), 1.73 (dd, J = 11.8, 5.1 Hz, 1 H), 1.63
(dd, J = 12.8, 4.9 Hz, 1 H), 1.57 (dd, J = 12.7, 5.1 Hz, 1 H).
13C-NMR (100 MHz, CDCl3): δ 171.2, 159.7, 154.3, 144.4,
138.2, 137.2, 135.1, 129.7, 129.0, 127.4, 120.9, 119.7,
114.1, 113.9, 103.2, 80.5, 66.5, 55.3, 54.6, 53.5, 52.1, 48.9,
39.2, 34.0, 22.0, 19.9. HRMS (ESI) m/z calcd for
C26H28O4Na [M + Na]+: 427.1880, found: 427.1881.
4-Cyanobenzyl(7S,9aS,10R)-7-hydroxy-1-methyl-8-
4-Chlorobenzyl(7S,9aS,10R)-7-hydroxy-1-methyl-8-
methylene-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo
[a]azulene-10-carboxylate (6e). Yield: 82.7% as a white
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solid. H-NMR (400 MHz, CDCl3): δ 7.36 (s, 4 H), 7.15 (t,
methylene-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo
[a]azulene-10-carboxylate (6h). Yield: 58.1% as a white
J = 7.5 Hz, 1 H), 7.02 (d, J = 7.5 Hz, 1 H), 6.95 (d, J =
7.3 Hz, 1 H), 5.23 (d, J = 12.3 Hz, 1 H), 5.19 (d, J =
12.3 Hz, 1 H), 5.00 (t, J = 2.5 Hz, 1 H), 4.74 (t, J = 2.0 Hz,
1 H), 4.02 (s, 1 H), 2.84 (dd, J = 12.6, 5.0 Hz, 1 H), 2.25
(dd, J = 13.2, 1.7 Hz, 1 H), 2.16 (d, J = 2.3 Hz, 1 H), 2.14
(d, J = 2.4 Hz, 1 H), 2.12 (s, 3 H), 2.10–2.07 (m, 1 H), 1.98
(dd, J = 12.2, 5.1 Hz, 1 H), 1.93 (dd, J = 9.4, 1.2 Hz, 1 H),
1.77–1.70 (m, 1 H), 1.62 (d, J = 4.9 Hz, 1 H), 1.58 (dd, J =
12.7, 5.2 Hz, 1 H). 13C-NMR (100 MHz, CDCl3): δ 171.1,
154.2, 144.4, 138.1, 135.0, 134.4, 134.2, 130.1 (×2), 129.0,
128.8 (×2), 127.5, 119.7, 103.3, 80.5, 65.8, 54.6, 53.5, 52.2,
48.9, 39.3, 34.0, 22.0, 19.9. HRMS (ESI) m/z calcd for
C25H25ClO3Na [M + Na]+: 431.1384, 433.1366, found:
431.1385, 433.1369 (3:1).
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solid. H-NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.3 Hz,
2 H), 7.51 (d, J = 8.3 Hz, 2 H), 7.15 (t, J = 7.6 Hz, 1 H),
7.01 (d, J = 7.5 Hz, 1 H), 6.95 (d, J = 7.3 Hz, 1 H), 5.32 (d,
J = 13.1 Hz, 1 H), 5.24 (d, J = 13.1 Hz, 1 H), 5.00 (t, J =
2.5 Hz, 1 H), 4.73 (t, J = 1.9 Hz, 1 H), 4.05 (s, 1 H), 2.85
(dd, J = 12.4, 4.8 Hz, 1 H), 2.28–2.22 (m, 1 H), 2.16 (dd,
J = 10.4, 2.3 Hz, 1 H), 2.13 (d, J = 2.3 Hz, 1 H), 2.09 (s,
3 H), 2.07 (d, J = 7.5 Hz, 1 H), 1.98 (dd, J = 12.4, 5.3 Hz,
1 H), 1.95–1.90 (m, 1 H), 1.77–1.71 (m, 1 H), 1.62 (d, J =
1.7 Hz, 1 H), 1.57 (dd, J = 12.7, 5.2 Hz, 1 H). 13C-NMR
(100 MHz, CDCl3): δ 171.2, 154.2, 144.6, 141.3, 138.2,
135.0, 132.6 (×2), 129.2, 129.0 (×2), 127.8, 120.0, 118.7,
112.1, 103.6, 80.5, 65.6, 54.7, 53.7, 52.3, 48.9, 39.8, 34.3,
22.2, 20.0. HRMS (ESI) m/z calcd for C26H25NO3Na [M +
Na]+: 422.1727, found: 422.1726.
3-(Trifluoromethyl)benzyl(7S,9aS,10R)-7-hydroxy-1-
methyl-8-methylene–4b,6,7,8,9,10-hexahydro-5H-7,9a-
methanobenzo[a]azulene-10-carboxylate (6f). Yield: 52.7%
2,3-Difluorobenzyl(7S,9aS,10R)-7-hydroxy-1-methyl-8-
methylene-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo
[a]azulene-10-carboxylate (6i). Yield: 65.5% as a white
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as a colorless oily liquid. H-NMR (400 MHz, CDCl3): δ
7.67 (s, 1 H), 7.59 (d, J = 7.7 Hz, 2 H), 7.52–7.47 (m, 1 H),
7.13 (t, J = 7.5 Hz, 1 H), 7.00 (d, J = 7.4 Hz, 1 H), 6.93 (d,
J = 7.3 Hz, 1 H), 5.30 (d, J = 12.6 Hz, 1 H), 5.25 (d, J =
12.5 Hz, 1 H), 4.96 (t, J = 2.6 Hz, 1 H), 4.70 (t, J = 2.0 Hz,
1 H), 4.02 (s, 1 H), 2.83 (dd, J = 12.4, 4.8 Hz, 1 H), 2.23
(dd, J = 13.2, 1.8 Hz, 1 H), 2.13 (dd, J = 9.8, 2.4 Hz, 1 H),
2.10 (d, J = 2.4 Hz, 1 H), 2.09 (s, 3 H), 2.06–2.04 (m, 1 H),
1.97–1.93 (m, 1 H), 1.92 (d, J = 2.8 Hz, 1 H), 1.72 (ddd,
J = 9.9, 5.3, 2.6 Hz, 1 H), 1.60 (d, J = 6.2 Hz, 1 H), 1.57 (d,
J = 5.2 Hz, 1 H). 13C-NMR (100 MHz, CDCl3): δ 171.2,
154.2, 144.5, 138.2, 136.9, 135.1, 132.1, 129.3(2 C), 129.2
(2 C), 127.7(2 C), 125.4(q, J = 260 Hz, 1 C), 119.9, 103.4,
80.6, 65.8, 54.7, 53.6, 52.3, 49.1, 39.4, 34.2, 22.1, 20.0.
HRMS (ESI) m/z calcd for C26H25F3O3Na [M + Na]+:
465.1648, found: 465.1645.
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solid. H-NMR (400 MHz, CDCl3): δ 7.27–7.22 (m, 1 H),
7.21–7.10 (m, 3 H), 7.05 (d, J = 5.5 Hz, 1 H), 6.98 (d, J =
5.4 Hz, 1 H), 5.39 (d, J = 12.2 Hz, 1 H), 5.31 (d, J =
15.8 Hz, 1 H), 5.04 (s, 1 H), 4.77 (s, 1 H), 4.06 (s, 1 H),
2.90–2.80 (m, 1 H), 2.37–2.22 (m, 3 H), 2.17 (s, 3 H),
2.10–2.05 (m, 1 H), 2.01 (dd, J = 12.4, 5.5 Hz, 1 H), 1.97
(d, J = 4.9 Hz, 1 H), 1.78 (d, J = 11.2 Hz, 1 H), 1.66 (d, J =
4.0 Hz, 1 H), 1.60 (d, J = 12.4 Hz, 1 H). 13C-NMR
(100 MHz, CDCl3): δ 171.0, 154.3, 144.4, 138.1, 135.0,
129.0, 127.5, 125.8, 125.5, 125.3, 124.2(d, J = 242 Hz,
1 C), 119.7, 117.8, 117.6(d, J = 238 Hz, 1 C), 103.2, 80.5,
60.0, 54.6, 53.5, 52.2, 48.9, 39.3, 34.1, 22.0, 19.8. HRMS
(ESI) m/z calcd for C25H24F2O3Na [M + Na]+: 433.1586,
found: 433.1585.
3-Methoxybenzyl(7S,9aS,10 R)-7-hydroxy-1-methyl-8-
methylene-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo
[a]azulene-10-carboxylate (6g). Yield: 58.2% as a yellow
3-Phenoxybenzyl(7S,9aS,10R)-7-hydroxy-1-methyl-8-
methylene-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo
[a]azulene-10-carboxylate (6j). Yield: 41.5% as a yellow
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1
oily liquid. H-NMR (400 MHz, CDCl3): δ 7.34–7.26 (m,
oily liquid. H-NMR (400 MHz, CDCl3): δ 7.42–7.34 (m,
2 H), 7.15 (t, J = 7.6 Hz, 1 H), 7.01 (t, J = 8.7 Hz, 2 H),
6.95 (d, J = 7.5 Hz, 1 H), 6.88 (dd, J = 7.9, 2.1 Hz, 1 H),
3 H), 7.21–7.16 (m, 3 H), 7.14 (s, 1 H), 7.08 (d, J = 8.5 Hz,
3 H), 7.00 (dd, J = 16.7, 8.5 Hz, 2 H), 5.28 (d, J = 12.4 Hz,