J. W. Huffman et al. / Bioorg. Med. Chem. 10 (2002) 4119–4129
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yellow solid: mp 109–110 ꢂC; 1H NMR (300 MHz,
CDCl3) d 0.82(t, J=7.2Hz, 3H), 1.03–1.13 (m, 2H),
1.10 (s, 3H), 1.25 (s, 6H), 1.43 (s, 3H), 1.50–1.55 (m,
2H), 1.79–1.93 (m. 2), 2.04–2.15 (m, 1H), 2.51–2.56 (m,
1H), 2.61 (td, J=4.5, 11.2Hz, 1H), 3.73 (dd, J=2.1,
17.9 Hz, 1H), 3 .82, (s, 3H), 6.39 (d, J=1.6 Hz, 1H), 6.42
(d, J=1.6 Hz, 1H), 6.83 (s, 1H), 9.50 (s, 1H); 13C NMR
(75.5 MHz, CDCl3) d 14.8, 17.9, 18.2, 27.5, 28.7, 29.2,
30.8, 37.6, 44.9, 47.0, 55.1, 75.8, 100.7, 108.2, 110.2,
142.2, 148.9, 150.1, 153.7, 158.6, 193.7; MS (EI) m/z 356
(55), 306 (100).
2.20–2.25 (m, 1H), 2.66 (td, J=4.6, 10.9 Hz, 1H), 3.31
(dd, J=3.6, 17.1 Hz, 1H), 3.80 (s, 3H), 4.05 (s, 2H), 5.73
(d, J=4.2Hz, 1H), 6.37 (d, J=1.6 Hz, 1H), 6.42(d,
J=1.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) d 14.1,
18.4, 23.4, 26.9, 27.6, 27.7, 28.8, 31.5, 31.8, 37.6, 44.2,
45.2, 67.1, 76.3, 100.6, 108.2, 111.1, 120.7, 138.5, 149.8,
153.8, 158.6; [a]D20 ꢁ284ꢂ (c=0.25, CHCl3); HRMS
calcd for C24H36O3: 372.2664, found 372.2663.
1-Methoxy -3- (10,10 -dimethylhexyl) - 11-oxo-D8 -THC
(14e). Selenium dioxide oxidation of 2.25 g (6.07 mmol)
of 6e, using the procedure described above for the pre-
paration of 10b gave 1.40 g (60%) of aldehyde 14e as an
orange solid, mp 117–119 ꢂC; 1H NMR (300 MHz,
CDCl3) d 0.83 (t, J=7.1 Hz, 3H), 1.02–1.30 (m, 6H),
1.10 (s, 3H), 1.25 (s, 6H), 1.43 (s, 3H), 1.51–1.56 (m,
2H), 1.80–1.93 (m, 2H), 2.05–2.18 (m, 1H), 2.49–2.56
(m, 1H), 2.62 (td, J=4.5, 11.2Hz, 1H), 3.73 (dd, J=4.1,
15.7 Hz, 1H), 3.82(s, 3H), 6.39 (d, J=1.6 Hz, 1H), 6.42
(d, J=1.6 Hz, 1H), 6.84 (br. s, 1H), 9.50 (s, 1H); 13C
NMR (75.5 MHz, CDCl3) d 14.1, 18.2, 22.5, 24.3, 27.5,
28.7, 28.8, 29.3, 30.9, 32.5, 37.7, 44.5, 44.9, 55.2, 75.8,
100.7, 108.1, 110.3, 142.5, 148.9, 150.2, 153.7, 158.7,
193.8; MS (EI) m/z 384 (20), 314 (100).
1-Methoxy-3-(10,10-dimethylbutyl)-11-hydroxy-D8-THC
(11c). To a suspension of 0.196 g (0.551 mmol) of alde-
hyde 14c in 3.5 mL of dry methanol was added sequen-
.
tially 0.205 g (0.551 mmol) of CeCl3 7H2O and 0.021 g
(0.551 mmol) of NaBH4. The reaction mixture was stir-
red at ambient temperature for 2h, the pH was adjusted
to 7.0 by the addition of 1M aqueous HCl. After pour-
ing into water the mixture was extracted with three
portions of CH2Cl2, dried (MgSO4) and the solvent was
removed in vacuo. The residue was purified by chroma-
tography (petroleum ether:ethyl acetate, 4:1) to give
0.185 g (94%) of cannabinoid 11c as a pale yellow gum:
1H NMR (500 MHz, CDCl3) d 0.82(t, J=7.1 Hz, 3H),
1.05–1.14 (m, 2H), 1.11 (s, 3H), 1.25 (s, 6H), 1.39 (s,
3H), 1.50–1.54 (m, 2H), 1.79–1.92 (m, 3H), 2.17–2.24
(m, 1H), 2.67 (td, J=4.6, 11.0 Hz, 1H), 3.31 (dd, J=4.6,
16.5 Hz, 1H), 3.80 (s, 3H), 4.05 (s, 2H), 5.73 (s, 1H),
6.38 (d, 1.6. 1H), 6.43 (d, J=1.6 Hz, 1H); 13C NMR
(125.8 MHz, CDCl3) d 14.7, 17.9, 18.3, 27.5, 27.6, 28.7,
28.8, 31.4, 31.8, 37.6, 45.1, 46.9, 55.0, 66.8, 76.2, 100.5,
108.1, 111.1, 120.4, 138.4, 149.6, 153.8, 158.5; [a]D20
ꢁ238ꢂ (c=0.50, CHCl3); HRMS calcd for C23H34O3:
358.2508, found 358.2509.
1-Methoxy-3-(10,10-dimethylhexyl)-11-hydroxy-D8-THC
(11e). Luche reduction of 0.404 g (1.05 mmol) of alde-
hyde 14e by the procedure described above for the
reduction of 14c gave after chromatography (petroleum
ether/ethyl acetate, 4:1) 0.354 g (87%) of 11-hydroxy
cannabinoid 11e as a pale yellow oil: 1H NMR
(300 MHz, CDCl3) d 0.83 (t, J=7.3 Hz, 3H), 1.07–1.34
(m, 6H), 1.11 (s, 3H), 1.25 (s, 6H), 1.40 (s, 3H), 1.51–
1.58 (m, 2H), 1.78–1.88 (m, 3H), 2.21–2.25 (m, 1H), 2.67
(td, J=4.6, 10.9 Hz, 1H), 3.31 (dd, J=3.5, 17.2Hz, 1H),
3.81 (s, 3H), 4.06 (s, 2H), 5.73 (d, J=4.4 Hz, 1H), 6.38
(d, J=1.6 Hz, 1H), 6.43 (d, J=1.6 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3) d 14.1, 18.4, 22.6, 24.3, 27.6, 27.7,
28.8, 28.9, 31.5, 31.9, 32.6, 44.4, 45.2, 55.2, 67.2, 76.3,
100.7, 108.3, 111.2, 120.8, 138.6, 149.9, 154.0, 158.7;
HRMS calcd for C25H38O3: 386.2821, found 386.2818.
1-Methoxy-3-(10,10 -dimethylpentyl)-11-oxo-D8 -THC
(14d). Selenium dioxide oxidation of 2.00 g (5.17 mmol)
of 6d, using the procedure described above for the pre-
paration of 10b, gave, after chromatography (petroleum
ether/ethyl acetate, 87.5:12.5), 1.17 g (50%) of aldehyde
14d as a pale orange solid: 1H NMR (300 MHz, CDCl3)
d 0.83 (t, J=7.4 Hz, 3H), 1.02–1.09 (m, 2H), 1.14 (s,
3H), 1.18–1.28 (m, 2H), 1.25 (s, 6H), 1.43 (s, 3H), 1.52–
1.60 (m, 2H), 1.76–1.94 (m, 2H), 2.05–2.19 (m, 1H),
2.53–2.58 (m, 1H), 2.61 (td, J=4.5, 11.2Hz, 1H), 3.74
(dd, J=3.6, 16.1 Hz, 1H), 3.83 (s, 3H), 6.39 (d,
J=1.6 Hz, 1H), 6.43 (d, J=1.6 Hz, 1H), 6.83–6.84 (m,
1H), 9.50 (s, 1H); 13C NMR (75 MHz, CDCl3) d 14.1,
18.2, 23.4, 26.9, 27.6, 28.7, 28.8, 29.2, 30.8, 37.9, 44.2,
45.0, 47.3, 55.1, 75.8, 100.7, 108.1, 110.2, 142.5, 148.9,
150.2, 153.7, 158.6, 193.8; MS (EI) m/z 370 (35), 314
(100), 300 (25).
3-(10,10 -Dimethylheptyl)-1-methoxy-11-oxo-D8 -THC
(14f). Selenium dioxide oxidation of 1.64 g (4.27 mmol)
of 4, using the procedure described above for the pre-
paration of 10b gave 1.12g (66%) of aldehyde 14f as an
orange solid: mp 118–119 ꢂC; Rf 0.31 (petroleum ether/
1
ethyl acetate, 94:6); H NMR (300 MHz, CDCl3) d 0.84
(t, J=6.9 Hz, 3H), 1.06–1.27 (m, 8H), 1.14 (s, 3H), 1.24
(s, 6H), 1.43 (s, 3H), 1.51–1.57 (m, 2H), 1.66–1.68 (m,
1H), 1.88 (td, J=4.1, 11.6 Hz, 1H), 2.07–2.18 (m, 1H),
2.51–2.57 (m, 1H), 2.61 (td, J=4.1, 11.2Hz, 1H), 3.73
(dd, J=4.5, 17.1 Hz, 1H), 3.81 (s, 3H), 6.39 (d,
J=1.6 Hz, 1H), 6.42(d, J=1.6 Hz, 1H), 6.83 (s, 1H),
9.50 (s, 1H); 13C NMR (75.5 MHz, CDCl3) d 14.1, 18.2,
22.6, 24.6, 27.5, 28.7, 28.9, 29.2, 30.0, 30.8, 31.7, 37.7,
44.5, 45.0, 55.1, 75.8, 100.7, 108.1, 110.2, 142.5, 148.9,
150.2, 153.7, 158.6, 193.8; MS (EI) m/z 398 (25), 314
(50), 281 (66), 207 (100).
1-Methoxy-3-(10,10-dimethylpentyl)-11-hydroxy-D8-THC
(11d). Luche reduction of 0.500 g (1.35 mmol) of alde-
hyde 14d by the procedure described above for the
reduction of 14c gave after chromatography (petroleum
ether/ethyl acetate, 4:1) 0.350 g (70%) of 11-hydroxy
cannabinoid 11d as a pale yellow gum: 1H NMR
(300 MHz, CDCl3) d 0.83 (t, J=7.3 Hz, 3H), 1.00–1.10
(m, 2H), 1.11 (s, 3H), 1.16–1.28 (m, 2H), 1.24 (s, 6H),
1.39 (s, 3H), 1.49–1.57 (m, 2H), 1.77–1.91 (m, 3H),
11-Hydroxy-3-(10,10-dimethylheptyl)-1-methoxy-D8-THC
(11f). Luche reduction of 0.314 g (0.789 mmol) of alde-
hyde 14f by the procedure described above for the