A. Jabbari et al. / Bioorg. Med. Chem. 20 (2012) 5518–5526
5525
cooled. The mixture was diluted with water (10 mL) and then ex-
tracted with ether (2 Â 20 mL). The combined extracts were
washed with NaOH 10% (2 Â 10 mL) and dried with anhydrous so-
dium carbonate. After removal of the solvent the products 11a–g,
12 and 13 were purified by column chromatography (Silicagel
60; 230–400; heptane).
–CH2– (allyl)), 4.52 (d, J = 6.0 Hz, 2H, (–CH2O–), 5.03–5.11 (m, 4H,
@CH2 (allyl) & @CH– (farnesyl)), 5.47 (t, J = 6.5 Hz, 1H, @CH– (far-
nesyl)), 5.95–6.01 (m, 1H, –HC@ (allyl), 6.81 (d, J = 8.5 Hz, 1H, H-2),
7.02 (s, 1H, NH), 7.21 (d, J = 2.5 Hz, 1H, H-5), 7.41 (dd, J = 8.5,
3.0 Hz, 1H, H-6); 13C NMR (CDCl3) d 172.94, 153.27, 140.47,
136.72, 135.38, 131.32, 130.91, 129.60, 124.33, 123.72, 121.80,
119.98, 118.94, 115.74, 112.22, 65.57, 40.47, 39.70, 39.52, 34.29,
26.71, 26.26, 25.72, 25.34, 18.06, 17.71, 16.70, 16.04. Found: C,
79.94; H, 9.40; N, 3.18. C29H41NO2 requires: C, 80.00; H, 9.42; N,
3.22.
4.2.8. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-adamantylbenzenamine (11a)
White solid, mp: 75–76 °C; 1H NMR (CDCl3): d 1.61, 1.62, 1.69 &
1.73 (s, 12H, CH3– (farnesyl)), 1.74–1.76 (m, 6H, –CH2– (adaman-
tyl)), 1.97 (m, 6H, –CH2– (adamantyl)), 1.99 (m, 2H, –CH2– (far-
nesyl)) 2.05–2.15 (m, 9H, –CH– (adamantyl) & –CH2– (farnesyl)),
3.38 (d, J = 6.5 Hz, 2H, –CH2– (allyl)), 4.52 (d, J = 5.0 Hz, 2H,
(–CH2O–), 5.04–5.11 (m, 4H, @CH2 (allyl) & @CH– (farnesyl)),
5.47 (t, J = 6.5 Hz, 1H, @CH– (farnesyl)), 5.95–6.01 (m, 1H, -H C@
(allyl), 6.81 (d, J = 9.0 Hz, 1H, H-2), 7.19 (s, 1H, NH), 7.22 (d,
J = 2.5 Hz, 1H, H-5), 7.40 (dd, J = 8.5, 3.0 Hz, 1H, H-6). 13C NMR
(CDCl3) d 175.84, 153.30, 140.45, 136.76, 135.38, 131.31, 130.93,
129.61, 124.33, 123.72, 122.05, 119.99, 119,19, 115.71, 112.72,
65.61, 41.31, 39.69, 39.52, 39.32, 36.47, 34.32, 28.16, 26.72,
26.27, 25.70, 17.70, 16.69, 16.03. Found: C, 81.81; H, 9.13; N,
2.69. C35H49NO2 requires: C, 81.50; H, 9.58; N, 2.72.
4.2.12. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-cyclopropylbenzenamine (11e)
White liqud; 1H NMR (CDCl3): d 0.81–0.85 (m, 2H, –CH2–,
(cyclopropyl)), 1.06–1.09 (m, 2H, –CH2–, (cyclopropyl)), 1.44–
1.47 (m, 1H, CH, (cyclopropyl)), 1.61, 1.62, 1.69 & 1.72 (s, 12H,
CH3– (farnesyl)), 1.97–2.15 (m, 8H, –CH2– (farnesyl)), 3.38 (d,
J = 6.5 Hz, 2H, –CH2– (allyl)), 4.52 (d, J = 6.5 Hz, 2H, (–CH2O–),
5.04–5.14 (m, 4H, @CH2 (allyl) & @CH– (farnesyl)), 5.46 (t,
J = 6.5 Hz, 1H, @CH– (farnesyl)), 5.94–6.00 (m, 1H, –HC@ (allyl),
6.81 (d, J = 8.5 Hz, 1H, H-2), 7.21 (d, J = 2.0 Hz, 1H, H-5), 7.25 (s,
1H, NH), 7.38 (dd, J = 8.5, 2.0 Hz, 1H, H-6); 13C NMR (CDCl3) d
171.50, 153.24, 140.47, 136.73, 135.39, 131.34, 131.05, 129.60,
124.33, 123.71, 121.84, 119.98, 118.94, 115.74, 112.21, 65.65,
39.70, 39.51, 34.29, 26.71, 26.25, 25.72, 17.71, 16.70, 16.04,
15.63. Found: C, 79.75; H, 9.21; N, 3.28. C28H39NO2 requires: C,
79.81; H, 9.26; N, 3.32.
4.2.9. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-cyclohexylbenzenamine (11b)
White solid, mp: 69–71 °C; 1H NMR (CDCl3): d 1.25–1.35 (m,
4H, –CH2– (cyclohexyl)), 1.52–1.55 (m, 2H, –CH2– (cyclohexyl)),
1.61, 1.62, 1.69 & 1.72 (s, 12H, CH3– (farnesyl)), 1.82–1.86 (m,
2H, –CH2– (farnesyl)), 1.94–2.00 (m, 4H, –CH2– (cyclohexyl & far-
nesyl)), 2.05–2.13 (m, 6H, –CH2– (cyclohexyl & farnesyl)), 2.17–
2.20 (m, 1H, CH, (cyclohexyl)), 3.38 (d, J = 7.0 Hz, 2H, –CH2– (allyl)),
4.52 (d, J = 6.5 Hz, 2H, (–CH2O–), 5.03–5.11 (m, 4H, @CH2 (allyl) &
@CH– (farnesyl)), 5.48 (t, J = 6.5 Hz, 1H, @CH– (farnesyl)), 5.95–
6.01 (m, 1H, –HC@ (allyl), 6.80 (d, J = 9.0 Hz, 1H, H-2), 7.13 (s,
1H, NH), 7.22 (d, J = 2.5 Hz, 1H, H-5), 7.41 (dd, J = 8.5, 2.5 Hz, 1H,
H-6); 13C NMR (CDCl3) d 174.1, 153.26, 140.47, 136.72, 135.38,
131.32, 130.99, 129.60, 124.33, 123.72, 121.88, 118.98, 118.02,
115.74, 112.23, 65.50, 46.43, 39.70, 39.52, 34.30, 29.72, 26.71,
26.62, 25.72, 17.71, 16.70, 16.04. Found: C, 80.29; H, 9.70; N,
2.98. C31H45NO2 requires: C, 80.30; H, 9.78; N, 3.02.
4.2.13. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-methylbenzenamine (11f)
White solid, mp: 60–61 °C; 1H NMR (CDCl3): d 1.61, 1.62, 1.69 &
1.72 (s, 12H, CH3– (farnesyl)), 1.97–2.00 (m, 2H, –CH2– (farnesyl)),
2.05–2.10 (m, 4H, –CH2– (farnesyl)), 2.12–2.17 (m, 5H, –CH2– (far-
nesyl) & CH3– (acetyl)), 3.37 (d, J = 6.5 Hz, 2H, –CH2– (allyl)), 4.52
(d, J = 6.5 Hz, 2H, (–CH2O–), 5.03–5.14 (m, 4H, @CH2 (allyl) &
@CH– (farnesyl)), 5.48 (t, J = 6.5 Hz, 1H, @CH– (farnesyl)), 5.93–
5.99 (m, 1H, –HC@ (allyl), 6.80 (d, J = 8.5 Hz, 1H, H-2), 7.15 (d,
J = 3.0 Hz, 1H, H-5), 7.30 (s, 1H, NH), 7.38 (dd, J = 8.5, 2.5 Hz, 1H,
H-6); 13C NMR (CDCl3) d 168.24, 153.49, 140.51, 136.72, 135.39,
131.32, 130.70, 129.58, 124.33, 123.71, 118.98, 118.49, 115.75,
111.15, 65.54, 39.70, 39.52, 34.29, 26.71, 26.26, 25.72, 24.36,
17.71, 16.70, 16.04. Found: C, 78.93; H, 9.34; N, 3.50. C26H37NO2 re-
quires: C, 78.99; H, 9.37; N, 3.54.
4.2.10. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-cyclopentyl benzenamine (11c)
White solid, mp: 29–30 °C; 1H NMR (CDCl3): d 1.57 (m, 2H,
–CH2– (cyclopentyl)),, 1.61, 1.62, 1.69 & 1.72 (s, 12H, CH3– (far-
nesyl)), 1.83 (m, 2H, –CH2– (cyclopentyl)), 1.82–1.86 (m, 2H,
4.2.14. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allylphenylbenzenamine (11g)
White solid, mp: 51–52 °C; 1H NMR (CDCl3): d 1.62, 1.63, 1.70 &
1.75 (s, 12H, CH3– (farnesyl)), 1.99–2.19 (m, 8H, –CH2– (farnesyl)),
3.40 (d, J = 7.0 Hz, 2H, –CH2– (allyl)), 4.55 (d, J = 6.5 Hz, 2H,
(–CH2O–), 5.05–5.16 (m, 4H, @CH2 (allyl) & @CH– (farnesyl)),
5.50 (t, J = 5.5 Hz, 1H, @CH– (farnesyl)), 5.95–6.00 (m, 1H, –HC@
(allyl), 6.85 (d, J = 8.5 Hz, 1H, H-2), 7.32 (s, 1H, NH), 7.44–7.47
(m, 2H, aromatic), 7.51–7.56 (m, 2H, aromatic), 7.85–7.88 (m, 2H,
aromatic); 13C NMR (CDCl3) d 165.60, 153.66, 140.55, 136.60,
135.40, 135.11, 131.60, 131.32, 130.79, 129.71, 128.68, 127.00,
124.36, 123.73, 122.43, 120.77, 119.96, 119.62, 115.62, 109.75,
65.57, 39.71, 39.53, 32.48, 26.73, 26.28, 25.70, 17.71, 16.72,
16.06. Found: C, 81.34; H, 8.50; N, 3.00. C31H39NO2 requires: C,
81.40; H, 8.53; N, 3.06.
–CH2– (farnesyl)), 1.94–2.00 (m, 4H, –CH2– (adamantyl
&
farnesyl)), 2.05–2.13 (m, 6H, –CH2– (adamantyl & farnesyl)), 2.18
(m, 1H, CH, (cyclohexyl)), 3.38 (d, J = 7.0 Hz, 2H, –CH2– (allyl)),
4.52 (d, J = 6.5 Hz, 2H, (-CH2O-), 5.03–5.11 (m, 4H, @CH2 (allyl) &
@CH– (farnesyl)), 5.48 (t, J = 6.5 Hz, 1H, @CH– (farnesyl)), 5.97 (m,
1H, –HC@ (allyl), 6.80 (d, J = 9.0 Hz, 1H, H-2), 7.13 (s, 1H, NH),
7.22 (d, J = 2.5 Hz, 1H, H-5), 7.41 (dd, J = 8.5, 2.5 Hz, 1H, H-6). 13C
NMR (CDCl3) d 173, 153, 140.50, 137, 135.60, 131.43, 131, 129.96,
124.45, 124, 122, 120, 119, 115.86, 112, 65.90, 34.42, 32.33, 27,
26.61, 26, 25.50, 18.08, 17.71, 16.73, 16.04. Found: C, 80.13; H,
69.52; N, 3.10. C30H43NO2 requires: C, 80.18; H, 9.58; N, 3.12.
4.2.11. 4-((2E,6E)-3,7,11-Trimethyldodeca-2,6,10-trienyloxy)-3-
allyl-N-cyclobutylbenzenamine (11d)
4.2.15. 4-((E)-3,7-Dimethyllocta-2,6-dienyloxy)-3-allyl-N-
adamantylbenzenamine (12)
Yellow solid, mp: 29–30 °C; 1H NMR (CDCl3): d 1.61, 1.62, 1.69
& 1.72 (s, 12H, CH3– (farnesyl)), 1.82–1.86 (m, 2H, –CH2– (far-
nesyl)), 1.94–2.15 (m, 10H, –CH2– (cyclobutyl & farnesyl)), 2.22–
2.24 (m, 2H, –CH2– (cyclobutyl)), 2.35–2.41 (m, 2H, –CH2–, (cyclo-
butyl)), 3.11–3.14 (m, 1H, CH, (cyclobutyl)), 3.38 (d, J = 7.0 Hz, 2H,
White solid, mp: 106–107 °C; 1H NMR (CDCl3): d 1.62, 1.69 &
1.72 (s, 9H, CH3– (geranyl)), 1.72–1.80 (m, 6H, –CH2– (adamantyl)),
1.97 (m, 6H, –CH2– (adamantyl)), 2.05–2.16 (m, 9H, –CH– (ada-
mantyl) & –CH2– (geranyl)), 3.38 (d, J = 6.5 Hz, 2H, –CH2– (allyl)),