H. Wu et al. / Bioorg. Med. Chem. 21 (2013) 5188–5197
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aqueous NaHCO3 (30 mL) were added to the reaction mixture. The
organic layer was separated and washed with H2O (30 mL), brine
(30 mL), dried over anhyd sodium sulfate, filtered, and concen-
trated to dryness under reduced pressure. The crude was purified
by flash chromatography on silica gel eluting with hexane/EtOAc
(3:1, v/v) to give the title compound as a white solid (578 mg,
86%). Mp 85–87° [lit.45 mp 94.5–95°, and46 fp 95.1°]; 1H NMR
(400 MHz, CDCl3) d 7.32–7.36 (m, 2H), 7.26–7.30 (m, 3H), 5.72
(br s, 1H), 4.45 (d, J = 6.0 Hz, 2H), 2.21 (t, J = 7.2 Hz, 2H), 1.61–
1.67 (m, 2H), 1.25–1.34 (m, 24H), 0.88 (t, J = 6.8 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) d 173.21, 138.66, 128.92, 128.05, 127.71,
43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56,
26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346.
43.82, 37.03, 31.75, 29.82, 29.57, 29.51, 29.48, 29.37, 27.42,
25.98, 25.85, 22.81, 14.31; LCMS, C25H39NO, [M+H]: 370.
4.1.7. (9Z,12Z)-N-(3-Methoxybenzyl)octadeca-9,12-dienamide
(6b)
It was prepared as described for 3a. Yield 75%. Colorless oil; 1H
NMR (400 MHz, CDCl3) d 7.23–7.27 (m, 1H), 6.86 (d, J = 7.2 Hz, 1H),
6.81–6.83 (m, 2H), 5.67 (br s, 1H), 5.29-5.40 (m, 4H), 4.42 (d,
J = 5.6 Hz, 2H), 3.80 (s, 3H), 2.77 (t, J = 6.8 Hz, 2H), 2.21 (t,
J = 7.6 Hz, 2H), 2.02–2.07 (m, 4H), 1.61–1.68 (m, 2H), 1.27–1.39
(m, 14H), 0.89 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) d
173.10, 160.13, 140.23, 130.46, 130.27, 129.98, 128.28, 128.13,
120.25, 113.62, 113.18, 55.46, 43.78, 37.05, 31.75, 29.83, 29.57,
29.52, 29.49, 29.37, 27.42, 25.98, 25.85, 22.81, 14.31; LCMS,
4.1.2. N-(3-Methoxybenzyl)palmitamide (3b)
C26H41NO2, [M+H]: 400.
It was prepared as described for 3a. Yield 73%. White powder,
mp 58–60°; 1H NMR (400 MHz, CDCl3) d 7.22–7.27 (m, 1H), 6.85
(d, J = 7.6 Hz, 1H), 6.80–6.82 (m, 2H), 5.68 (br s, 1H), 4.42 (d,
J = 6.0 Hz, 2H), 3.80 (s, 3H), 2.21 (t, J = 7.2 Hz, 2H), 1.61–1.69 (m,
2H), 1.25–1.34 (m, 24H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3,
4.1.8. (9Z,12Z,15Z)-N-Benzyloctadeca-9,12,15-trienamide (7a)
It was prepared from linolenic acid as described for 3a. Yield
85%. Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.26–7.35 (m, 5H),
5.73 (br s, 1H), 5.30–5.41 (m, 6H), 4.44 (d, J = 5.2 Hz, 2H), 2.80 (t,
J = 6.4 Hz, 4H), 2.21 (t, J = 7.6 Hz, 2H), 2.02–2.11 (m, 4H), 1.62–
1.67 (m, 2H), 1.30–1.36 (m, 8H), 0.97 (t, J = 7.6 Hz, 3H); 13C NMR
100 MHz)
d 173.18, 160.13, 140.23, 129.98, 120.25, 113.60,
113.19, 55.46, 43.78, 37.07, 32.16, 29.92, 29.90, 29.89, 29.84,
29.73, 29.59, 29.57, 26.01, 22.92, 14.35; LCMS,
[M+H]: 376.
C
24H41NO2,
(CDCl3, 100 MHz) d 173.14, 138.64, 132.20, 130.49, 128.94,
128.51, 128.48, 128.06, 127.95, 127.74, 127.34, 43.82, 37.03,
29.80, 29.51, 29.47, 29.36,27.43, 25.98, 25.85, 25.75, 20.78, 14.51;
LCMS, C25H37NO, [M+H]: 368.
4.1.3. N-Benzylstearamide (4)
Prepared from stearic acid by the method for 3a. Yield 85%.
White powder, mp 84–86° [lit.46 fp 99.2°]; 1H NMR (400 MHz,
CDCl3) d 7.32–7.36 (m, 2H), 7.26–7.30 (m, 3H), 5.68 (br s, 1H),
4.45 (d, J = 6.0 Hz, 2H), 2.21 (t, J = 7.6 Hz, 2H), 1.65–1.69 (m, 2H),
1.25–1.29 (m, 28H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3,
100 MHz) d 173.20, 138.64, 128.94, 128.07, 127.73, 43.82, 37.06,
32.16, 29.93, 29.84, 29.73, 29.60, 26.01, 22.93, 14.36; LCMS,
4.1.9. (9Z,12Z,15Z)-N-(3-Methoxybenzyl)octadeca-9,12,15-
trienamide (7b)
It was prepared as described for 3a. Yield 80%. Colorless oil; 1H
NMR (400 MHz, CDCl3) d 7.23–7.27 (m, 1H), 6.86 (d, J = 7.2 Hz, 1H),
6.81–6.83 (m, 2H), 5.67 (br s, 1H), 5.29–5.41 (m, 6H), 4.42 (d,
J = 6.0 Hz, 2H), 3.80 (s, 3H), 2.80 (t, J = 6.8 Hz, 4H), 2.21 (t,
J = 7.6 Hz, 2H), 2.02–2.10 (m, 4H), 1.61–1.68 (m, 2H), 1.30–1.36
(m, 8H), 0.97 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz) d
173.10, 160.13,140.22, 132.21, 130.50, 129.98, 128.52, 128.48,
127.96, 127.34, 120.26, 113.63, 113.18, 55.46, 43.78, 37.05, 29.81,
29.52, 29.48, 29.36, 27.43, 25.98, 25.85, 25.75, 20.78, 14.51; LCMS,
C25H43NO, [M+H]: 374.
4.1.4. N-Benzyloleamide (5a)
It was prepared from oleic as described for 3a. White powder.
Yield 82%. Mp 48–50° [lit.46 fp 58.8°]; 1H NMR (400 MHz, CDCl3)
d 7.32–7.36 (m, 2H), 7.26–7.29 (m, 3H), 5.72 (br s, 1H), 5.32–5.37
(m, 2H), 4.44 (d, J = 6.0 Hz, 2H), 2.21 (t, J = 7.6 Hz, 2H), 1.98–2.03
(m, 4H), 1.63–1.67 (m, 2H), 1.26–1.30 (m, 20H), 0.88 (t,
J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) d 173.20, 138.63,
130.23, 129.98, 128.94, 128.06, 127.74, 43.81, 37.03, 32.13, 30.00,
29.93, 29.76, 29.56, 29.52, 29.49, 29.37, 27.45, 27.40, 26.00,
22.92, 14.36; LCMS, C25H41NO, [M+H]: 372.
C26H39NO2, [M+H]: 398.
4.1.10. (Z)-N-Benzyltetracos-15-enamide (8)
It was prepared from nervonic acid as described for 3a. Yield
94%. White powder, mp 64–66°; 1H NMR (400 MHz, CDCl3) d
7.26–7.36 (m, 5H), 5.68 (br s, 1H), 5.31–5.39 (m, 2H), 4.44 (d,
J = 6.0 Hz, 2H), 2.21 (t, J = 7.6 Hz, 2H), 1.98–2.04 (m, 4H), 1.62–
1.69 (m, 2H), 1.25–1.29 (m, 32H), 0.88 (t, J = 6.8 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) d 173.17, 138.64, 130.13, 128.94, 128.07,
127.74, 43.83, 37.07, 32.13, 30.01, 29.89, 29.84, 29.80, 29.75,
29.73, 29.58, 29.55, 27.44, 26.01, 22.91, 14.35; LCMS, C31H53NO,
[M+H]: 456.
4.1.5. N-(3-Methoxybenzyl)oleamide (5b)
It was prepared as described for 3a. Yield 49%. Colorless oil; 1H
NMR (400 MHz, CDCl3) d 7.23–7.27 (m, 2H), 6.86 (d, J = 7.2 Hz, 1H),
6.81–6.83 (m, 3H), 5.67 (br s, 1H), 5.32–5.36 (m, 2H), 4.42 (d,
J = 6.0 Hz, 2H), 3.80 (s, 1H), 2.21 (t, J = 7.2 Hz, 2H), 2.03–1.88 (m,
4H), 1.61–1.68 (m, 2H), 1.26–1.30 (m, 20H), 0.88 (t, J = 6.8 Hz,
3H); 13C NMR (CDCl3, 100 MHz) d 173.12, 160.11, 140.21, 130.23,
129.99, 129.98, 120.25, 113.61, 113.19, 55.46, 43.78, 37.06, 32.13,
30.00, 29.93, 29.76, 29.56, 29.53, 29.49, 29.37, 27.45, 27.40,
26.00, 22.92, 14.36; LCMS, C26H43NO2, [M+H]: 402.
4.1.11. (1E,3E)-1-Bromotrideca-1,3-diene (9i)
To neat 1-undecyne (2.28 g, 15.0 mmol) was added slowly dii-
sobutylaluminum hydride (1.0 M in heptane; 15 ml, 15.0 mmol)
at room temperature. The reaction was heated at 50° for 18 h.
The heptane was removed under reduced pressure to give (1E)-dii-
sobutyl-1-undecenylaluminum as an oil. The oil was diluted with
dry THF (6 ml) and with stirring was slowly added to a mixture
of tetrakis(triphenylphosphine)palladium(0) (347 mg, 0.3 mmol)
and dibromoethylenes (13.8 g, 75.0 mmol, 60% cis and 40% trans)
in dry THF (4 ml) under N2. After 24 h at room temperature the
reaction mixture was quenched with 3 N HCl (5 ml) and extracted
with diethyl ether (60 ml). The organic layer was washed with satd
NaHCO3 (20 ml), H2O (20 mL) and brine (20 ml), dried over sodium
sulfate and concentrated to dryness. The crude product (oil) was
purified by flash chromatography on silica gel eluting with hexanes
4.1.6. (9Z,12Z)-N-Benzyloctadeca-9,12-dienamide (6a)
It was prepared from linoleic acid as described for 3a. Yield 84%.
White powder, mp 30–32° [lit.46 fp 35.8°]; 1H NMR (400 MHz,
CDCl3) d 7.26–7.36 (m, 5H), 5.73 (br s, 1H), 5.30–5.40 (m, 4H),
4.44 (d, J = 5.6 Hz, 2H), 2.77 (t, J = 6.4 Hz, 2H), 2.21 (t, J = 8.0 Hz,
2H), 2.02–2.07 (m, 4H), 1.63–1.67 (m, 2H), 1.26–1.37 (m, 14H),
0.89 (t, J = 6.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz) d 173.15,
138.64, 130.46, 130.27, 128.94, 128.27, 128.13, 128.06, 127.74,