A. Madrigal et al. / Tetrahedron: Asymmetry 11 (2000) 3515–3526
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and was then poured onto ice water. The combined organic layers were dried over sodium
sulphate and evaporated under reduced pressure. The residue was used in the next reaction
without further purification.
1
Data for 14: H NMR (CDCl3) l: 8.66 (s, 1H, H-7), 7.41 (d, 1H, H-8, J=7 Hz), 7.3 (d, 1H,
H-11, J=7 Hz), 7.10 (m, 2H, H-9 and 10), 5.54 (d, 1H, H-6eq, J=16.5 Hz), 4.14 (m, 5H, H-3,
H-12a, H-6ax and OCH2CH3), 3.07 (dd, 1H, H-12eq, J=6.7 and 19.5 Hz), 2.75 (m, 1H,
H-12ax), 1.47 (d, 3H, (C-3)-CH3, J=7.2 Hz), 1.35 (t, 3H, OCH2CH3, J=7 Hz) ppm.
1
Data for 15: H NMR (CDCl3) l: 8.74 (s, 1H, H-7), 7.44 (d, 1H, H-8, J=7.5 Hz), 7.29 (d,
1H, H-11, J=7.5 Hz), 7.10 (m, 2H, H-9 and H-10), 5.5 (d, 1H, H-6eq, J=16.5 Hz), 4.2 (m, 5H,
H-3, H-12a, H-6ax, and OCH2CH3), 3.28 (dd, 1H, H-12eq, J=4.0 and 14.8 Hz), 2.78 (m, 1H,
H-12ax), 1.02 (d, 3H, (C-3)-CH3, J=7 Hz), 1.02 (t, 3H, OCH2CH3, J=7 Hz) ppm.
1
Data for 16: H NMR (CDCl3) l: 8,69 (s, 1H, H-7), 7.5 (d, 1H, H-8, J=7.7 Hz), 7.34 (d, 1H,
H-11, J=7.7 Hz), 7.15 (m, 2H, H-9 and H-10), 6, 34 (s, 1H, H-6), 4.47 (m, 1H, H-12a), 4.25 (m,
2H, H-3), 4.17 (q, 2H, OCH2CH3, J=7 Hz), 3.78 (s, 3H, OCH3), 3.38 (dd, 1H, H-12eq, J=4.0
and 15.5 Hz), 2.81 (dd, 1H, H-12ax, J=15.5 and 12.0 Hz), 1.35 (t, 3H, OCH2CH3, J=7 Hz)
ppm.
3.7. Synthesis of 7,10,16,16a-tetrahydroquinazolino[2%,3%:3,4]pyrazino[1,2-b]i-carboline-5,8-
diones. General method. Synthesis of (+)-18, (−)-18, and 19
A mixture of the corresponding iminoether (0.88 mmol) and anthranilic acid (3 equiv.) was
melted at 130°C under stream of argon for 2 h. The melt was cooled and triturated with 20%
aqueous ammonium hydroxide (2 ml), and the mixture was extracted with chloroform. The
combined organic layers were dried over anhydrous sodium sulphate and evaporated under
reduced pressure. The residue was chromatographed on silica gel as previously described, and
the final purification was performed by a second column chromatography eluting with
dichloromethane.
Starting from 14 (0.1 g, 0.33 mmol) and anthranilic acid (0.138 g, 1.01 mmol) a yield of 0.03
g (24%) of (−)-18 was obtained.
Data for (−)-18: mp: 235–236°C. IR (KBr): 3297 (NH), 1660 and 1628 (CONH) and 1622
1
(CꢀN) cm−1. H NMR (CDCl3) l: 8.35 (s, 1H, H-11), 8.29 (d, 1H, H-4, J=7 Hz), 7.79 (t, 1H,
H-2, J=7 Hz), 7.7 (d, 2H, H-1, J=7 Hz), 7.54 (m, 2H, H-3 and 15), 7.37 (d, 1H, H-12, J=7.5
Hz), 7.20 (m, 2H, H-13 and 14), 5.8 (d, 1H, H-10eq, J=16.2 Hz), 5.47 (q, 1H, H-7, J=7 Hz),
5.0 (dd, 1H, H-16a, J=11.8 and 4.2 Hz), 4.26 (d, 1H, H-10ax, J=16.3 Hz), 3.67 (dd, 1H,
H-16eq, J=4.9 and 11.8 Hz), 3.18 (m, 1H, H-16ax), 1.64 (d, 3H, (C-7)-CH3, J=7 Hz) ppm. 13C
NMR (CDCl3) l: 166.4 y 160.8 (C-8 and C-5)*, 150.1 (C-16b), 147.5 and 136.3 (C-17a and
C-4a)*, 135.0 (C-4), 132.5 (C-15a), 129.1 (C-15b), 127.3 (C-1), 127.1 (C-2), 127.0 (C-3), 126.6
(C-11a), 122.6 (C-14), 120.2 (C-13), 118.11 (C-12), 111.3 (C-15), 107.3 (C-15b), 58.3 (C-16a),
52.0 (C-7), 38.8 (C-10), 29.8 (C-16), 20.3 ((C-10)-CH3) ppm. Anal. calcd for C22H18N4O2: C,
71.34; H, 4.90; N, 15.13. Found: C, 71.86; H, 5.01; N, 15.02. [h]2D5 −353 (c 0.07, CHCl3).
Starting from 15 (0.15 g, 0.5 mmol) and anthranilic acid (0.207 g, 1.5 mmol) a yield of 0.056
g (30%) of (+)-18 was obtained.
Data for (+)-18, with the exception of the specific rotation value, were identical to those of
compound (−)-18. [h]2D5 +350 (c 0.07, Cl3CH).
Starting from 16 (0.3 g, 0.88 mmol) and anthranilic acid (0.361 g, 2.64 mmol), a yield of 0.116
g (32%) of 19 was obtained.