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1773
exhaustively extracted with CH2Cl2. The combined CH2Cl2 solutions were
washed with brine, dried (Na2SO4), and then evaporated in vacuo to give an
essentially pure 10a in 93% yield. Mp 98–100 °C (lit., mp 97–100 °C); FTIR
(KBr): 1760 cm1, 1H NMR (400 MHz, CDCl3), d: 3.90 (3H, s), 4.07 (3H, s), 5.22
(2H, s), 7.21 (1H, d, J = 7.8 Hz), 7.47 (1H, d, J 7.8 Hz). Compound 10b was
obtained following the same procedure in 91% yield.
Acknowledgments
L.S.S. thanks FONDECYT (Project 1085308). M.D.P.C.S. thanks to
PBCT (PSD-50) for financial support.
20. Martin, S. F.; Bur, S. K. Tetrahedron 1999, 55, 8905–8914.
References and notes
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22. Imine 4 was synthesized as described by Ref. 15: yellow solid. 1H NMR (300 MHz,
CDCl3), d: 2.58–2.72 (2H, m), 3.65–3.74 (2H, m), 6.00 (2H, s), 6.61 (1H, s), 6.74
(1H, s), 8.17 (1H, t, J = 2.3 Hz); 13C NMR (75 MHz, CDCl3), d: 25.2, 47.1, 101.3,
107.6, 108.1, 122.6, 131.8, 146.5, 149.2, 159.5.
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N. E.; Holland, H. L.; MacLean, D. B. Can. J. Chem. 1973, 51, 32873293. Mp 135–
137 °C (lit., mp 136–140 °C). 1H NMR (400 MHz, CDCl3), d: 2.21–2.33 (2H, m),
2.42–2.66 (2H, m), 2.55 (3H, s), 2.83–2.95 (1H, m), 3.90 (3H, s), 4.00, (1H, d,
J = 3.5 Hz,), 4.05 (3H, s), 5.49 (1H, d, J = 3.5 Hz), 5.89 (2H, s), 6.39 (1H, s), 6.58
(1H, s), 6.52 (1H, d, J = 7.0 Hz), 7.08 (1H, d, J = 7.0 Hz). 13C NMR (100 MHz,
CDCl3), d: 26.7, 44.7, 49.0, 56.7, 62.0, 66.0, 82.7, 100.5, 107.3, 108.1, 117.3,
118.5, 119.4, 124.5, 130.0, 140.4, 145.4, 146.0, 147.5, 152.6, 167.0. HRMS,
ESI(+)MS: m/z calcd for [C21H21NO6+H]+: 384.1447, found: 384.1439. (b) epi-
Noscapine (threo-2a) is in accordance with; Seitanidi, K. L.; Yagudaev, M. R.;
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CDCl3), d: 2.40–2.81 (3H, m), 2.54 (3H, s), 2.99–3.10 (1H, m), 3.85 (3H, s), 3.99
(3H, s), 4.01, (1H, d, J = 3.4 Hz), 5.53 (1H, d, J = 3.4 Hz), 5.78 (1H, d, J = 1.3 Hz),
5.83 (1H, d, J = 1.3 Hz), 6.37 (1H, s), 6.65 (1H, s), 7.04 (1H, d, J = 8.4 Hz), 7.29
(1H, d, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3), d: 29.2, 44.9, 51.3, 56.7, 62.2,
66.2, 81.8, 100.7, 107.4, 108.2, 118.1, 118.4, 119.3, 125.3, 130.0, 141.1, 145.8,
146.3, 147.6, 152.3, 168.0. HRMS, ESI(+)MS: m/z calcd for [C21H21NO6+H]+:
384.1447, found: 384.1455.
26. (a) Bicuculline (erythro-1b) data is in accordance with: Teitel, S.; O’Brien, J.;
Brossi, A. J. Org. Chem. 1972, 37, 1879–1881. Mp 225–227 °C (lit., mp 227–
229 °C). 1H NMR (400 MHz, CDCl3), d: 2.23–2.31 (1H, m), 2.51–2.62 (2H, m),
2.83–2.90 (1H, m), 2.54 (3H, s), 4.05 (1H, d, J = 4.3 Hz), 5.56 (1H, d, J = 4.3 Hz),
5.92 (1H, d, J = 1.1 Hz), 6.17 (2H, d, J = 1.7 Hz), 6.19 (1H, d, J = 8.0 Hz), 6.91 (1H,
d, J = 8.0 Hz), 6.47 (1H, s), 6.58 (1H, s). HRMS, ESI(+)MS: m/z calcd for
[C20H17NO6+H]+: 368.1134, found: 368.1145. (b) Capnoidine (threo-2b) data is
in accordance with Ref. 26a: mp 202–204 °C (lit., mp 200–203 °C). 1H NMR
(400 MHz, CDCl3), d: 2.39–2.80 (1H, m), 2.53 (3H, s), 3.01–3.10 (1H, m), 4.04,
(1H, d, J = 3.4 Hz), 5.62 (1H, d, J = 3.4 Hz), 5.83 (2H, s), 6.11 (2H, s), 6.40 (1H, s),
6.66 (1H, s), 6.94 (1H, d, J = 8.0 Hz), 7.14 (1H, d, J = 8.0 Hz). HRMS, ESI(+)MS: m/
z calcd for [C20H17NO6+H]+: 368.1134, found: 368.1142.
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Morimoto, Y.; Iwahashi, M. Synlett 1995, 12–21; (e) Zanardi, F.; Battistini, L.;
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6997; (b) Santos, L. S.; Pilli, R. A. Tetrahedron Lett. 2001, 42, 6999–7001; (c)
Santos, L. S.; Pilli, R. A. J. Braz. Chem. Soc. 2003, 14, 982–993; (d) Shankaraiah,
N.; Pilli, R. A.; Santos, L. S. Tetrahedron Lett. 2008, 49, 5098–5100.
15. Henry, T. A.; Sharp, T. M. J. Chem. Soc. 1930, 2279–2285.
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19. Morpholine (12 mmol) and THF (20.0 mL) were placed in a 100 mL flask, and a
solution of the bromoaldehyde (7a or 7b, 10 mmol) in 20.0 mL of THF was
placed in a dropping funnel. The mixture in the flask was cooled with stirring
to 50 °C, and n-butyllithium (1.6 M in hexane, 7.5 mL, 12 mmol) was added all
at once. After 5 min, the solution of the aldehyde was added from the dropping
funnel over a period of 1 min, and the resulting mixture was cooled to 80 °C
over 15 min. n-Butyllithium (1.6 M in hexane, 10 mL, 16 mmol) was then
added dropwise, keeping the temperature at or below 75 °C. After the addition
was over (5 min), the mixture was stirred at 80 °C for 35 min, and then a large
excess of solid CO2 was added at once. After 1 h, the mixture was allowed to
reach room temperature and was acidified to pH 1 with 6 M HCl. The solution
after dilution with brine was extracted with Et2O (4 ꢂ 30 mL) and then
exhaustively with EtOAc. The combined organic layers were washed with
brine, dried (Na2SO4), and evaporated in vacuo to give the crude
phthalaldehydic acids 9a,b. The crude product was recrystallized from H2O
to give 85% of 9a: mp 142–145 °C; FTIR (KBr): 3443, 1762, 1605 cm1; 1H NMR
(400 MHz, acetone-d6), d: 3.93 (6H, s), 6.51 (1H, br s), 7.35 (2H, br s). Next, to a
stirred solution or suspension of the 9a (2 mmol) in 15 mL of CH2Cl2 and
NaBH4 (3.2 mmol) at 78 °C was added TMSOTf (2 mmol) dropwise. The mixture
was stirred at 78 °C for 2 h and then at 25 °C for 12 h. Then the mixture was
evaporated in vacuo and the residue was treated, diluted with brine, and then
27. (a) Egenine (1c): 1H NMR (400 MHz, CDCl3), d: 1.75–1.85 (1H, m), 1.96–2.04
(1H, m), 2.35–2.43 (1H, m), 2.50 (3H, s), 2.66–2.75 (1H, m), 3.89 (1H, d,
J = 3.5 Hz), 5.41 (1H, d, J = 3.5 Hz), 5.66 (1H, d, J = 7.7 Hz), 5.95 (2H, d,
J = 1.2 Hz), 6.02 (2H, d, J = 1.2 Hz), 6.35 (1H, s), 6.52 (1H, d, J = 7.7 Hz), 6.59
(1H, s), 6.81 (1H, s). 13C NMR (100 MHz, CDCl3), d: 22.3, 44.0, 45.9, 65.0, 87.0,
98.0, 100.9, 101.6, 107.5, 108.4, 108.5, 114.5, 124.0, 124.2, 128.6, 133.1, 141.5,
146.4, 146.7, 148.2. HRMS, ESI(+)MS: m/z calcd for [C20H19NO6+H]+: 370.1291,
found: 370.1299. (b) Corytensine (2c): 1H NMR (400 MHz, CDCl3), d: 1.95 (3H,
s), 2.36–2.48 (2H, m), 2.91–2.93 (1H, m), 3.10–3.14 (1H, m), 3.69 (1H, s), 5.25
(1H, s), 5.88 (1H, s), 5.95 (1H, s), 6.05 (1H, s), 6.08 (1H, s), 6.27 (1H, s), 6.60 (1H,
s), 6.70 (1H, s), 6.83 (2H, d, J = 8.5). 13C NMR (100 MHz, CDCl3), d: 29.1, 46.6,
53.8, 68.5, 89.9, 97.6, 100.7, 101.8, 106.7, 108.3, 108.8, 113.9, 124.1, 128.7,
130.5, 135.2, 141.5, 146.0, 146.3, 148.1. HRMS, ESI(+)MS: m/z calcd for
[C20H19NO6+H]+: 370.1291, found: 370.1283.
28. (a) Shono, T.; Hamaguchi, H.; Sasaki, M.; Fujita, S.; Nagami, K. J. Org. Chem.
1983, 48, 1621–1628; (b) Shono, T.; Miyamoto, T.; Mizukami, M.; Hamaguchi,
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29. Bur, S. K.; Martin, S. F. Org. Lett. 2000, 2, 3445–3447.