216
E. Reimann and M. Renz
2150.48 (0.75)); IR (KBr): ꢃꢀ¼ 2239 (CN), 1671=1641 (CO)
cmꢄ1; MS (EI): m=z (%) ¼ 490 (20), 459 (6), 258 (17), 203
(100), 131 (32), 105 (48), 77 (35).
119.63, 52.73 (C-11b), 47.79 (C-3), 40.05 (C-6), 32.84
(C-1), 32.49 (Cꢁ), 32.49 (C-2), 28.93 (C-7), 20.76 (C-12),
12.74 (C-13) ppm.
18a: 1H NMR (CDCl3): ꢀ ¼ 7.56–7.52 (m, 3 arom H),
7.46–7.42 (m, 2 arom H), 7.26, 6.62, 6.60, and 6.48 (each s,
each 1H, 4 arom H), 6.39 and 5.72 (each d, J ¼ 7.8 and 7.9Hz,
3-H and 4-H), 4.84–4.76 (m, 1H), 4.48 (dd, J ¼ 10.7=5.2 Hz,
11b-H), 3.96, 3.91, 3.86, and 3.80 (4s, 4 OCH3), 2.83–2.74
(2 m, each 1H), 2.63 (m, 1H), 2.43–2.29 (m, 5H), 1.60–1.40
(m, 3H), 0.93 (t, J ¼ 7.4 Hz, CH3) ppm; 13C NMR (CDCl3):
ꢀ ¼ 171.54 (CO), 169.59 (CO), 149.95, 149.33, 147.91,
147.84, 133.23, 131.98, 129.26 (2C), 128.93, 128.68 (2C),
126.91, 124.93, 122.22, 121.26, 118.21, 111.57, 110.00,
108.34 (2C), 107.41, 59.59, 56.47, 56.11, 56.03, 55.92, 55.67
(C-11b), 47.19 (C-3), 40.31 (Cꢁ), 39.26 (C-6), 34.30 (C-1),
30.85 (C-2), 28.66 (C-7), 20.81 (C-12), 12.88 (C-13) ppm.
18b: 1H NMR (CDCl3): ꢀ ¼ 7.63–7.44 (m, 6 arom H), 6.62,
6.59, and 6.47 (each s, each 1 arom H), 6.44 and 5.69 (each
d, J ¼ 7.9 and 8.1 Hz, 3-H and 4-H), 4.81–4.72 (m, 1H), 4.44
(dd, J ¼ 11.2=5.1 Hz, 11b-H), 3.96, 3.91, 3.85 and 3.82 (4s,
4 OCH3), 2.86–2.14 (m, 8H), 1.43–1.35 (m, 3H), 0.88 (t,
J ¼ 7.4 Hz, CH3) ppm; 13C NMR (CDCl3): ꢀ ¼ 170.22 (CO),
169.40 (CO), 150.11, 149.09, 147.90, 147.84, 133.12, 131.96,
129.31 (2C), 128.67 (2C), 127.76, 126.78, 125.30, 122.35,
120.27, 118.36, 111.58, 110.44, 108.37, 107.98, 106.56,
59.61, 56.39, 56.01, 55.63, 55.36, 54.75 (C-11b), 47.40
(C-3), 40.42 (Cꢁ), 39.45 (C-6), 33.99 (C-1), 30.36 (C-2),
28.58 (C-7), 20.71 (C-12), 12.87 (C-13) ppm.
General Procedure for the Synthesis of the Diastereomeric
4-Oxoemetamines 20 and 21
A mixture of the Reissert compound 17 or 18, MeOH, and
12% KOH was heated at 70ꢂC for 1 h. After removing the
solvent in vacuo, the residue was taken up in a small quantity
of CHCl3, and purified by FC (EtOAc:MeOH ¼ 9:1).
(2S,3R,11bS = 2R,3S,11bR)-2-(6,7-Dimethoxyisoquinolin-
1-ylmethyl)-3-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-
hexahydro-2H-benzo[a]quinolizin-4-one (20, C29H34N2O5)
Starting from 1.1 g (1.77 mol) 17, 55cm3 MeOH, 2.86cm3
(26.4 mmol) KOH. Yield: 800 mg (92%) colourless oil, which
on treatment with Et2O gave a colourless amorphous solid; mp
169–172ꢂC; TLC (see FC): Rf ¼ 0.32 (educt: Rf ¼ 0.64); IR
(KBr): ꢃꢀ¼ 1633 (CO) cmꢄ1; MS (EI): m=z (%) ¼ 490 (Mþ
ꢃ,
48), 459 (8), 286 (17), 258 (100), 203 (38), 190 (40); 1H NMR
(CDCl3): ꢀ ¼ 8.35 and 7.45 (each d, each J ¼ 5.6 Hz, 30-H and
40-H), 7.33, 7.10, 6.59 and 6.31 (each s, each 1H, 50-H, 80-H,
8-H, and 11-H), 5.16 (dd, J ¼ 10.3=5.6 Hz, 11b-H), 4.97–4.89
(m, 1H, 6-H), 4.04, 4.02, 3.83, and 3.67 (each s, each OCH3),
3.53 and 3.06 (each dd, J ¼ 14.0=4.2 and 13.9=12.2 Hz, each
1H, ꢁ-CH2), 2.98–2.88 (m, 2H), 2.69–2.61 (m, 1H), 2.46–
2.34 (m, 2H), 2.23 (dt, J ¼ 13.5=5.2 Hz, 1H), 1.77–1.64 (m,
2H), 1.19 (t, J ¼ 7.4 Hz, CH3) ppm; 13C NMR (CDCl3):
ꢀ ¼ 170.87 (CO), 157.48, 152.66, 150.19, 147.65, 147.52,
140.71, 133.23, 130.03, 127.22, 122.87, 118.49, 111.55,
107.95, 105.55, 103.16, 56.04 (2 OCH3), 55.60 (OCH3),
55.84 (OCH3), 52.52 (C-11b), 47.70 (C-3), 40.21 (C-7),
32.98 (C-1), 32.73 (Cꢁ), 32.02 (C-2), 28.46 (C-7), 20.58
(C-12), 12.56 (C-13) ppm.
(2R,3R,11bS)-3-Ethyl-2-isoquinolin-1-ylmethyl-
1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizin-4-
one (11, C25H26N2O)
A suspension of 526 mg (1.05 mmol) of the diastereomeric
mixture 10 in 15 cm3 MeOH and 0.95g (2mmol) 12% KOH
was stirred at ambient temperature until the reaction was
complete (about 1 h, TLC monitoring). After removing the
solvent in vacuo, the residue was dissolved in 20cm3 H2O.
The solution was acidified with 2N HCl and washed with
3ꢅ20 cm3 EtOAc. The aqueous layer was rendered alkaline
with 50% KOH and extracted with 3ꢅ30 cm3 of the same
solvent. The combined organic extracts were washed with 1N
NaOH, dried (Na2SO4), and concentrated in vacuo giving a
colourless residue, which crystallized from n-hexane (15 h).
Yield: 313 mg (81%) colourless crystals; mp 133–134ꢂC; TLC
(n-hexane:EtOAc¼ 1:1): Rf ¼ 0.2 (educt: Rf ¼ 0.4); IR (film):
(2S,3R,11bR=2R,3S,11bS)-2-(6,7-Dimethoxyisoquinolin-1-
ylmethyl)-3-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-
2H-benzo[a]quinolizin-4-one (21, C29H34N2O5)
Starting from 123 mg (0.23 mol) 18, 5 cm3 MeOH, 0.4 cm3
(3.7mmol) KOH. Yield: 101mg (90%) colourless oil; TLC
(see FC): Rf ¼ 0.35 (educt: Rf ¼ 0.66); IR (film): ꢃꢀ¼ 1632
(CO) cmꢄ1; MS (EI): m=z (%) ¼ 490 (Mþ
ꢃ, 15), 459 (9),
1
286 (10), 258 (19), 203 (100), 190 (8), 97 (10); H NMR
(CDCl3): ꢀ ¼ 8.36 and 7.42 (each d, J ¼ 5.6 and 5.4Hz, 30-H
and 40-H), 7.20, 7.08, 6.56, and 6.50 (each s, each 1H, 50-H,
80-H, 8-H, and 11-H), 4.85–4.81 (m, 1H, 6-H), 4.54 (dd,
J ¼ 10.3=5.8 Hz, 11b-H), 4.03, 4.02, 3.82, and 3.75 (each s,
each OCH3), 3.35 and 3.10 (each dd, J ¼ 14.5=4.7 and
14.5=9.9 Hz, each 1H, ꢁ-CH2), 2.99–2.89 (m, 2-H), 2.91–
2.78 and 2.66–2.62 (each m, 2H and 1H, 7-H and 6-H),
2.56 (dt, J ¼ 8.1=5.1 Hz, 3-H), 2.44 (dt, J ¼ 13.6=4.9 Hz, 1H,
1-H), 1.90–1.69 (m, 1-H and CH2), 1.09 (t, J ¼ 7.3 Hz, CH3)
ppm; 13C NMR (CDCl3): ꢀ ¼ 172.20 (CO), 156.86, 152.57,
150.02, 147.72, 147.61, 140.76, 133.10, 129.32, 126.89,
123.09, 118.37, 111.44, 108.33, 105.51, 103.00, 56.03 (3
OCH3), 55.80 (OCH3), 55.66 (C-11b), 46.74 (C-3), 39.72
(C-6), 36.50 (Cꢁ), 33.94 (C-2), 33.14 (C-1), 28.68 (C-7),
20.79 (C-12), 13.14 (C-13) ppm.
ꢃꢀ¼ 1632 (CO) cmꢄ1; MS (EI): m=z (%) ¼ 370 (Mþ
ꢃ, 35), 198
(100), 143 (83) 130 (42); 1H NMR (CDCl3): ꢀ ¼ 8.46 (d,
J ¼ 5.6 Hz, 30-H), 8.15 and 7.86 (each d, J ¼ 8.4=8.0 Hz, each
1 arom H), 7.70–7.55 and 7.14–7.05 (each m, each 3 arom
H), 6.82 (d, J ¼ 7.7 Hz, 1 arom H), 5.19 (dd, J ¼ 10.9=5.7 Hz,
11b-H), 4.94–4.86 (m, 1H, 6-H), 3.63 and 3.14 (each dd,
J ¼ 14.2=4.3 and 14.1=11.9 Hz, CH2), 3.01–2.97 (m, 2H,
6-H and 7-H), 2.92–2.87 and 2.79–2.74 each m, each
1H), 2.44–2.34 (m, 2H), 2.29 (dt, J ¼ 13.5=5.1 Hz, 1H,
1-H), 1.77–1.60 (m, 2H), 1.18 (t, J ¼ 7.4 Hz, CH3) ppm;
13C NMR (CDCl3): ꢀ ¼ 170.96 (CO), 160.07 (C-10),
141.76 (C-30), 138.25, 136.37, 134.97, 129.95, 128.83,
127.64, 127.29, 127.11, 126.36, 126.25, 124.79, 124.39,