Journal of Natural Products
Article
6
.99 (1H, d, J = 7.9 Hz), 6.90 (2H, d, J = 11.6 Hz), 6.51 (1H, s), 6.21
(15 mL) was stirred at room temperature for 2.5 h. Pyridine was
evaporated, and the residual solids were dissolved in CH Cl (50 mL).
(
1H, s), 5.89 (1H, s), 3.40 (1H, dd, J = 6.7 Hz), 3.29 (1H, dd, J = 6.8
2
2
Hz), 2.90−2.95 (1H, m), 2.81−2.85 (2H, m), 2.28 (1H, d), 1.96−1.99
The resulting solution was washed with 5% HCl (3 × 50 mL) and
(
2H, m), 1.67−1.80 (3H, m), 1.49 (2H, d, J = 11.9 Hz), 1.31−1.41
water (3 × 50 mL), dried with anhydrous Na SO , and evaporated to
2
4
(
2H, m), 1.23 (3H, s), 1.23 (3H, s), 1.22 (3H, s), 0.99 (3H, s); 13
C
give the amide 6 as a pale yellow solid (0.95 g, 71%): mp 208 °C;
[α]2 +42.2 (c 1.0, CHCl ); IR (neat) ν 3266, 2929, 1705, 1692,
5
NMR (CDCl , 125 MHz) δ 161.2, 147.0, 145.6, 134.7, 126.9, 125.9,
3
D
3
max
−1
1
1
24.2, 123.8, 121.4, 109.6, 108.3, 49.7, 45.6, 38.3, 37.7, 37.5, 36.3, 33.4,
1524, 1497, 1279, 1215, 1038, 883, 626, 593, 407 cm ; H NMR
+
30.4, 25.4, 23.9, 19.1, 18.7, 18.6; HRMS [M + Na] m/z 401.2570
(CDCl , 500 MHz) δ 7.73−7.61 (1H, m), 7.15 (1H, d, J = 8.4 Hz),
3
(
calcd for C H N ONa 401.2569).
(
6.98 (1H, dd, J = 8.4, 1.5 Hz), 6.89 (1H, d, J = 1.1 Hz), 6.43 (1H, d, J
= 12.8 Hz), 6.23 (1H, d, J = 12.8 Hz), 3.43 (1H, dd, J = 13.7, 7.0 Hz),
3.16 (1H, dd, J = 13.7, 6.2 Hz), 2.97−2.75 (3H, m), 2.29 (1H, d, J =
12.8 Hz), 1.97−1.86 (1H, m), 1.83−1.63 (3H, m), 1.50−1.27 (4H,
25
34
2
E)-N-(Dehydroabietyl)-3-phenylprop-2-enamide (4). A mix-
ture of dehydroabietylamine (1) (5.0 g, 18 mmol), cinnamoyl chloride
4.4 g, 0.030 mol), and DMAP (3.2 g, 26 mmol) in pyridine (100 mL)
(
1
3
was stirred at 40 °C for 24 h. Solvents were evaporated, the solid
residue was dissolved in toluene (400 mL), and the resulting solution
was washed with 5% HCl (3 × 200 mL), water (150 mL), a saturated
m), 1.22 (3H, s), 1.21 (3H, s), 1.20 (3H, s), 0.98 (3H, s); C NMR
(CDCl , 125 MHz) δ 166.6, 166.0, 146.9, 145.7, 135.9, 134.6, 132.0,
3
127.0, 124.1, 50.8, 45.1, 38.0, 37.5, 36.1, 33.4, 30.0, 25.4, 24.0, 19.1,
+
aqueous solution of NaHCO (2 × 150 mL), and water (150 mL).
18.8, 18.5; HRMS m/z [M + H] 384.2540 (calcd for C H NO
3
24 34
3
The organic layer was dried with anhydrous Na SO , and the filtrate
384.2539).
2
4
was evaporated. The obtained product was dried in a vacuum oven at
N-(Dehydroabietyl)butanamide (7). A mixture of dehydroabie-
tylamine (1) (1.0 g, 3.5 mmol), butanoyl chloride (0.36 mL, 3.5
mmol), triethylamine (0.50 mL, 3.6 mmol), and DMAP (0.39 g, 3.5
mmol) in pyridine (20 mL) was stirred at room temperature for 1 h.
Pyridine was evaporated, and the residual solids were dissolved in
4
7
1
0 °C overnight to give the amide 4 as a white solid (5.05 g, 70%): mp
25
2 °C; [α] −8.2 (c 1.0, CHCl ); IR (neat) ν 3287, 2924, 2865,
D
3
max
−
1 1
655, 1617, 1547, 1449, 1334, 1217, 976, 821, 763, 680, 486 cm ; H
NMR (CDCl , 500 MHz) δ 7.62 (1H, d, J = 15.6 Hz), 7.49 (2H, dd, J
3
=
7.9, 1.8 Hz), 7.30−7.40 (3H, m), 7.17 (1H, d, J = 8.2 Hz), 6.99 (1H,
CH
× 50 mL) and water (3 × 50 mL), dried with anhydrous Na
evaporated to give the amide 7 as a yellow solid (0.68 g, 55%): mp 70
Cl
2
2
(50 mL). The resulting solution was washed with 5% HCl (3
dd, J = 8.1, 1.5 Hz), 6.36 (1H, d, J = 15.4 Hz), 6.90 (1H, s), 5.56 (1H,
t, J = 5.9 Hz), 3.25 (1H, dd, J = 13.3, 6.7 Hz), 3.37 (1H, dd, J = 13.7,
2
SO , and
4
2
5
6
(
1
(
.4 Hz), 2.77−2.98 (3H, m), 2.30 (1H, d, J = 12.8 Hz), 1.90−1.97
1H, m), 1.65−1.85 (3H, m), 1.44−1.50 (1H, m), 1.27−1.44 (2H, m),
.19−1.25 (9H, m), 1.03 (1H, t, J = 7.3 Hz), 0.99 (1H, s), 0.83−0.92
1H, m); 13C NMR (CDCl , 125 MHz) δ 166.0. 147.1, 145.6, 141.0,
°C; [α]
1642, 1547, 1456, 1381, 1208, 820, 629 cm ; H NMR (CDCl , 500
3
D 3
+24.6 (c 1.0, CHCl ); IR (neat) νmax 3304, 2958, 2926, 2868,
−1 1
MHz) δ 7.17 (1H, d, J = 8.2 Hz), 7.00 (1H, dd, J = 8.2, 7.7 Hz), 6.90
(1H, d, J = 1.3 Hz), 5.46 (1H, t, J = 5.9 Hz), 3.20 (1H, dd, J = 13.7, 6.3
Hz), 3.13 (1H, dd, J = 13.7, 6.7 Hz), 2.96−2.76 (3H, m), 2.32−2.24
(1H, m), 2.13 (2H, td, J = 7.5, 3.6 Hz), 1.93−1.85 (1H, m), 1.82−1.59
(6H, m), 1.44−1.38 (2H, m), 1.38−1.33 (1H, m), 1.26−1.19 (11H,
3
1
1
2
34.8, 134.8, 129.5, 129.0, 128.7, 128.2, 127.7, 126.9, 125.2, 124.1,
23.8, 120.8, 49.8, 45.2, 38.3, 37.6, 37.4, 36.2, 33.4, 30.1, 25.2, 23.9,
3.9, 18.9, 18.8, 18.6; HRMS m/z [M + Na] 438.2775 (calcd for
+
m); 13C NMR (CDCl
, 125 MHz) δ 173.1, 147.1, 145.6, 126.9, 124.2,
C H NONa 438.2773).
3
29
37
(
E)-N-(Dehydroabietyl)-3-(4-nitrophenyl)prop-2-enamide
123.9, 49.7, 45.4, 39.0, 38.3, 37.4, 37.3, 36.2, 33.4, 30.2, 25.3, 24.0,
19.3, 18.9, 18.7, 18.6, 13.8; HRMS m/z [M + Na] 378.2773 (calcd for
+
(
5). A mixture of 4-nitrocinnamic acid (10.0 g, 51.8 mmol), thionyl
chloride (38.0 mL, 524 mmol), and a drop of N,N-dimethylformamide
was stirred at 40 °C for 21 h. Solvents were evaporated, and the
resulting solids were dissolved in chloroform (100 mL). Chloroform
was evaporated, and the treatment was repeated three times to remove
residual thionyl chloride. The crude product was obtained as a yellow
solid (14.4 g) and used in the next reaction step without further
purification. A mixture of dehydroabietylamine (1) (5.0 g, 18 mmol),
C H NONa 378.2773).
2-(Dehydroabietylcarbamoyl)benzoic acid (8). A mixture of
24
37
dehydroabietylamine (1) (1.0 g, 3.5 mmol), phthalic anhydride (0.52
g, 3.5 mmol), triethylamine (0.50 mL, 3.6 mmol), and DMAP (0.39 g,
3.5 mmol) in pyridine (15 mL) was stirred at room temperature for 2
h. Pyridine was evaporated, and the residual solids were dissolved in
CH Cl (50 mL). The resulting solution was washed with 5% HCl (3
2
2
4
-nitrocinnamoyl chloride (4.1 g, 19 mmol), and DMAP (2.4 g, 20
× 50 mL) and water (3 × 50 mL), dried with anhydrous Na SO , and
2 4
mmol) in pyridine (100 mL) was stirred at 40 °C for 24 h. The
precipitate formed was filtered off, and the filtrate was evaporated. The
residue was dissolved in toluene (400 mL) and washed with 5% HCl
evaporated to give the amide 8 as a pale yellow solid (0.73 g, 48%):
25
mp 81 °C; [α]D +6.0 (c 1.0, CHCl ); IR (neat) ν 2925, 1736, 1676,
3
max
−1
1
1534, 1454, 1296, 1167, 1107, 820, 695, 631, 437 cm ; H NMR
(
3 × 200 mL), water (150 mL), a saturated aqueous solution of
(CDCl , 500 MHz) δ 7.87 (1H, d, J = 7.5 Hz), 7.47−7.39 (1H, m),
3
NaHCO (2 × 150 mL), and water (150 mL). The organic layer was
dried with anhydrous Na SO and evaporated. The crude product (5.7
g) was purified with SiO column chromatography (hexane−EtOAc,
1
7.39−7.33 (2H, m), 7.15 (1H, d, J = 8.3 Hz), 6.98 (1H, d, J = 8.3, 1.8
Hz), 6.88 (1H, d, J = 1.2 Hz), 6.77−6.67 (1H, m), 3.31 (1H, dd, J =
13.9, 6.7 Hz), 3.18 (1H, dd, J = 13.9, 5.8 Hz), 2.95−2.70 (3H, m), 2.26
(1H, d, J = 12.3 Hz), 1.92−1.80 (1H, m), 1.78−1.65 (3H, m), 1.65−
3
2
4
2
:2). The product was dried in a vacuum oven at 60 °C overnight to
yield the amide 5 as a yellow solid (3.4 g, 42%): mp 102−107 °C;
1.57 (1H, m), 1.47−1.38 (2H, m), 1.38−1.25 (3H, m), 1.22 (3H, s),
2
5
13
[
1
α] −16.6 (c 1.0, CHCl ); IR (neat) ν 3294, 2929, 1658, 1622,
1.20 (3H, s), 1.09 (3H, s), 0.94 (3H, s); C NMR (CDCl , 125 MHz)
D
3
max
3
−1
1
517, 1340, 1215, 978, 843, 822, 719, 630, 482 cm ; H NMR
δ 171.0, 169.8, 147.0, 145.5, 137.3, 134.7, 132.0, 129.8, 129.6, 127.9,
(
CDCl , 500 MHz) δ 8.21 (2H, d, J = 8.8 Hz), 7.66 (1H, d, J = 15.6
126.9, 124.2, 123.8, 50.8, 45.9, 38.2, 37.5, 37.4, 36.0, 33.3, 30.2, 25.4,
24.0, 18.9, 18.5, 18.5; HRMS m/z [M + H] 434.2696 (calcd for
3
+
Hz), 7.62 (2H, d, J = 8.8 Hz), 7.18 (1H, d, J = 8.0 Hz), 7.00 (1H, dd, J
8.2, 1.7 Hz), 6.90 (1H, d, J = 1.2 Hz), 6.10 (1H, d, J = 15.6 Hz), 5.71
1H, t, J = 6.3 Hz), 3.23 (1H, dd, J = 13.8, 6.7 Hz), 3.42 (1H, dd, J =
=
(
C H NO 434.2695).
25
39
3
N-(Dehydroabietyl)acetamide (9). A mixture of dehydroabietyl-
1
3.9, 6.4 Hz), 2.95 (1H, dd, J = 17.3, 6.3 Hz), 2.77−2.89 (2H, m), 2.31
amine (1) (1.0 g, 3.5 mmol), acetic anhydride (0.33 mL, 3.5 mmol),
triethylamine (1.0 mL, 7.2 mmol), and DMAP (0.39 g, 3.5 mmol) in
pyridine (15 mL) was stirred at room temperature for 2 h. Pyridine
was evaporated, and the residual solids were dissolved in CH Cl (50
(
1H, d, J = 13.0 Hz), 1.88−1.97 (1H, m), 1.58−1.85 (1H, m), 1.47
(
1
2H, dd, J = 12.5, 2.4 Hz), 1.40 (1H, dd, J = 13.1 Hz, 3.7 Hz), 1.27−
.43 (3H, m), 1.19−1.26 (9H, m), 1.03 (1H, t, J = 7.3 Hz), 0.99 (1H,
2
2
13
s), 0.70−0.91 (1H, m); C NMR (CDCl , 125 MHz) δ 164.8, 148.1,
mL). The resulting solution was washed with 5% HCl (3 × 50 mL)
3
1
1
2
47.1, 145.8, 141.1, 138.5, 134.7, 128.3, 126.9, 125.0, 124.1, 124.1,
23.9, 49.9, 46.2, 45.1, 38.3, 37.7, 37.4, 36.2, 33.4, 30.1, 25.2, 24.0,
and water (3 × 50 mL), dried with anhydrous Na SO , and evaporated
2
4
to give the amide 9 as a pale yellow solid (0.77 g, 67%): mp 58−64 °C;
+
25
3.9, 19.0, 18.9, 18.8, 18.6; HRMS m/z [M + Na] 483.2634 (calcd for
[α] +30.4 (c 1.0, CHCl ); IR (neat) ν 3295, 2925, 2865, 1647,
D
3
max
−1 1
C H N O Na 483.2624).
1554, 1440, 1374, 1287, 820, 599 cm ; H NMR (CDCl , 500 MHz)
29
36
2
3
3
(
Z)-N-(Dehydroabietyl)-3-carboxyprop-2-enamide (6). A mix-
δ 7.17 (1H, d, J = 8.2 Hz), 7.00 (1H, dd, J = 8.2, 3.3 Hz), 6.90 (1H, d,
J = 1.2 Hz), 5.57−5.42 (1H, m), 3.23 (1H, dd, J = 13.8, 6.4 Hz), 3.08
(1H, dd, J = 13.7, 6.6 Hz), 2.97−2.77 (2H, m), 2.33−2.24 (1H, m),
ture of dehydroabietylamine (1) (1.0 g, 3.5 mmol), maleic anhydride
0.34 g, 3.5 mmol), and triethylamine (1.0 mL, 7.2 mmol) in pyridine
(
E
J. Nat. Prod. XXXX, XXX, XXX−XXX