Y. Morimoto et al.
FULL PAPER
acetate 76:24 to 52:48) on silica gel (80 g) to furnish methyl acetal 30
(2.39 g, 90.0%) as a colorless oil: Rf 0.66 (benzene/ethyl acetate 50:50);
15 mL). The organic layer was washed with brine, dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure. The residue
was subjected to column chromatography (chloroform/acetone 84:16 to
76:24) on silica gel to provide alcohol 33 (156 mg, 82.1%) as a colorless oil:
[a]2D7
12.6 (c 0.943 in CHCl3); 1H NMR (400 MHz, CDCl3, 258C,
TMS): d 7.26 (d, J 8.5 Hz, 2H), 6.88 (d, J 9.2 Hz, 2H), 5.20 (brs, 1H),
4.95 (brs, 1H), 4.88 ± 4.84 (m, 1H), 4.42 (s, 2H), 3.98 (brd, J 9.2 Hz, 1H),
3.80 (s, 3H), 3.73 (s, 3H), 3.43 (t, J 6.1 Hz, 2H), 3.33 (brs, 3H), 2.85 (brs,
1H), 2.75 (ddd, J 11.6, 6.7, 4.3 Hz, 1H), 2.67 (dd, J 17.1, 6.7 Hz, 1H),
2.42 (d, J 17.1 Hz, 1H), 2.16 (dq, J 4.0, 11.9 Hz, 1H), 1.99 (dd, J 11.6,
4.9 Hz, 1H), 1.69 ± 1.32 (m, 7H); IR (film): nÄ 2950, 2875, 1790, 1710, 1615,
1517, 1445, 1374, 1305, 1248, 1200, 1155, 1130, 1098, 1083, 1035, 1000, 979,
Rf 0.40 (chloroform/acetone 80:20); [a]D27
105.0 (c 0.855 in CHCl3);
1H NMR (400 MHz, CDCl3, 258C, TMS): d 5.90 ± 5.75 (m, 1H), 5.13 (d,
J 8.5 Hz, 1H), 5.10 (d, J 15.9 Hz, 1H), 4.51 (brs, 1H), 3.90 ± 3.60 (m,
1H), 3.68 (s, 3H), 3.67 ± 3.57 (m, 2H), 3.38 ± 3.24 (m, 1H), 3.25 (dt, J 5.8,
11.2 Hz, 1H), 2.70 ± 2.33 (m, 1H), 2.52 (dq, J 2.6, 7.5 Hz, 1H), 2.32 ± 2.14
(m, 3H), 2.04 (ddd, J 11.3, 5.5, 2.8 Hz, 1H), 1.99 (dt, J 11.3, 5.7 Hz, 1H),
1.93 ± 1.20 (m, 8H), 1.39 (dq, J 8.3, 11.7 Hz, 1H), 1.31 (d, J 7.3 Hz, 3H);
IR (film): nÄ 3475, 2950, 1775, 1690, 1640, 1458, 1380, 1297, 1200, 1160,
939, 900, 820, 755, 736 cm 1; MS (FAB): m/z (%): 586 (7.4) [M H] , 556
(53); HR-MS (FAB): found: 586.1243 [M H] ; C25H33O7NI calcd
586.1302; elemental analysis calcd (%) for C25H34INO7 (587.4): C 51.11,
H 5.83, N 2.38; found: C 51.00, H 5.78, N 2.39.
1113, 1055, 1013, 990, 920, 775, 730 cm 1; MS (EI): m/z (%): 365 (16) [M] ,
322 (42), 306 (33), 292 (33), 260 (30), 167 (100), 141 (23), 81 (21), 69 (29), 55
(23); HR-MS (EI): found: 365.2184 [M] ; C20H31O5N calcd 365.2202;
Allylation product 31: Azobis(isobutyronitrile) (78.3 mg, 0.477 mmol) and
allyltributyltin (3.45 mL, 11.1 mmol) were added at room temperature
under a nitrogen atmosphere to a solution of methyl acetal 30 (1.87 g,
3.18 mmol) in toluene (7.0 mL), and the solution was stirred at 808C for 4 h.
After the solution had been cooled to room temperature, the reaction
mixture was concentrated under reduced pressure. The residue was
subjected to column chromatography (benzene/ethyl acetate 76:24 to
52:48) on silica gel (112 g) to afford allylation product 31 (1.28 g, 80.0%) as
elemental analysis calcd (%) for C20H31NO5 (365.5): C 65.73, H 8.55, N
3.83; found: C 65.85, H 8.50, N 3.81.
Aldehyde 34: A catalytic amount of osmium tetroxide was added at room
temperature to a solution of alcohol 33 (156 mg, 0.427 mmol) and sodium
metaperiodate (274 mg, 1.28 mmol) in tetrahydrofuran (4.0 mL) and water
(2.0 mL), and the solution was vigorously stirred at the same temperature
for 1 h. Water (25 mL) was added, and the aqueous layer was extracted with
dichloromethane (3 Â 20 mL). The organic layer was washed with brine,
dried over anhydrous magnesium sulfate, and concentrated in vacuo. The
residue was purified by column chromatography (chloroform/methanol
96:4 to 92:8) on silica gel to yield aldehyde 34 (117 mg, 74.5%) as a
a colorless oil: Rf 0.47 (benzene/ethyl acetate 50:50); [a]D27
52.5 (c
1
1.20 in CHCl3); H NMR (400 MHz, CDCl3, 258C, TMS): d 7.25 (d, J
8.5 Hz, 2H), 6.87 (d, J 8.5 Hz, 2H), 5.80 (ddt, J 16.9, 10.2, 7.0 Hz, 1H),
5.18 (brs, 1H), 5.12 (d, J 8.5 Hz, 1H), 5.09 (d, J 16.5 Hz, 1H), 4.42 (s,
2H), 4.38 (brs, 1H), 3.80 (s, 3H), 3.70 (s, 3H), 3.42 (t, J 6.7 Hz, 2H),
3.42 ± 3.28 (m, 1H), 3.33 (brs, 3H), 2.66 (dd, J 17.4, 7.0 Hz, 1H), 2.37 (d,
J 16.5 Hz, 1H), 2.45 ± 2.12 (m, 6H), 1.97 (dd, J 12.2, 4.9 Hz, 1H), 1.70 ±
1.22 (m, 7H); IR (film): nÄ 2950, 2870, 1780, 1710, 1615, 1517, 1447, 1378,
1310, 1248, 1200, 1170, 1115, 1085, 1035, 996, 945, 897, 820, 780 cm 1; MS
colorless oil: Rf 0.48 (chloroform/methanol 90:10); [a]D27
103.1 (c
1.04 in CHCl3); 1H NMR (400 MHz, CDCl3, 258C, TMS): d 9.79 (s, 1H),
4.45 (brs, 1H), 3.85 ± 3.60 (m, 1H), 3.68 (s, 3H), 3.61 (t, J 5.8 Hz, 2H),
3.43 ± 3.18 (m, 2H), 2.80 ± 2.40 (m, 2H), 2.52 (dq, J 4.9, 7.3 Hz, 1H), 2.15 ±
1.20 (m, 11H), 2.04 (dt, J 11.6, 5.8 Hz, 1H), 1.43 (dq, J 8.5, 12.0 Hz, 1H),
1.30 (d, J 7.3 Hz, 3H); IR (film): nÄ 3450, 2950, 2880, 1775, 1690, 1460,
1452, 1383, 1357, 1335, 1270, 1205, 1160, 1125, 1025, 990, 930, 775, 733,
(FAB): m/z (%): 500 (2.6) [M H] , 470 (23); HR-MS (FAB): found:
500.2628 [M H] ; C28H38O7N calcd 500.2648; elemental analysis calcd
(%) for C28H39NO7 (501.6): C 67.04, H 7.84, N 2.79; found: C 66.99, H 7.90,
N 2.76.
700 cm 1; MS (EI): m/z (%): 367 (19) [M] , 294 (16), 168 (17), 167 (100), 69
(16), 55 (20); HR-MS (EI): found: 367.2010 [M] ; C19H29O6N calcd
367.1995; elemental analysis calcd (%) for C19H29NO6 (367.4): C 62.11, H
7.96, N 3.81; found: C 62.19, H 7.94, N 3.77.
Lactone 32: n-Butyllithium (1.6m in hexane, 0.886 mL, 1.43 mmol) was
added dropwise at 08C under a nitrogen atmosphere to a solution of
diisopropylamine (0.201 mL, 1.43 mmol) in tetrahydrofuran (5.0 mL), and
the solution was stirred at the same temperature for 30 min. After the
Dithiolane 35: 1,2-Ethanedithiol (32.1 mL, 0.382 mmol) and boron trifluor-
ide etherate (47.0 mL, 0.382 mmol) were added dropwise at 158C under a
nitrogen atmosphere to a solution of aldehyde 34 (117 mg, 0.318 mmol) in
dichloromethane (4.0 mL), and the solution was stirred at the same
temperature for 45 min. Water (10 mL) was added at 158C, and the
resulting mixture was allowed to warm to room temperature with stirring.
The aqueous layer was extracted with dichloromethane (3 Â 10 mL). The
organic layer was washed with brine, dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure. The residue was
subjected to column chromatography (chloroform/methanol 98:2 to 96:4)
on silica gel to furnish dithiolane 35 (114 mg, 80.9%) as a colorless oil: Rf
solution had been cooled to
788C, hexamethylphosphoric triamide
(1.54 mL, 8.88 mmol) and lactone 31 (359 mg, 0.716 mmol) dissolved in
tetrahydrofuran (6.0 mL) were added dropwise, and the solution was
stirred at the same temperature for 30 min. Iodomethane (0.469 mL,
7.52 mmol) was added dropwise at 788C, and the solution was stirred at
the same temperature for an additional 1.5 h. Saturated aqueous ammo-
nium chloride (3.0 mL) was added at 788C, and the resulting mixture was
allowed to warm to room temperature, with stirring. The reaction mixture
was poured into water (30 mL), and the aqueous layer was extracted with
diethyl ether (3 Â 30 mL). The organic layer was washed with brine, dried
over anhydrous magnesium sulfate, and concentrated in vacuo. The residue
was purified by column chromatography (benzene/ethyl acetate 76:24 to
68:32) on silica gel to give lactone 32 (268 mg, 72.6%), an intermediate
common to stenine (1) and tuberostemonine (2), as a colorless oil: Rf 0.49
0.56 (chloroform/methanol 90:10); [a]D29
73.7 (c 1.14 in CHCl3);
1H NMR (400 MHz, CDCl3, 258C, TMS): d 4.66 (t, J 6.4 Hz, 1H),
4.52 ± 4.45 (m, 1H), 3.90 ± 3.64 (m, 1H), 3.69 (s, 3H), 3.62 (t, J 6.1 Hz,
2H), 3.33 ± 3.18 (m, 6H), 2.64 ± 2.28 (m, 2H), 2.53 (dq, J 2.0, 7.4 Hz, 1H),
2.05 (ddd, J 11.6, 4.9, 2.1 Hz, 1H), 1.99 (dt, J 11.6, 6.1 Hz, 1H), 2.08 ±
1.22 (m, 10H), 1.38 (dq, J 9.2, 11.8 Hz, 1H), 1.31 (d, J 7.3 Hz, 3H); IR
(film): nÄ 3475, 2940, 1770, 1690, 1452, 1382, 1355, 1270, 1202, 1160, 1115,
(benzene/ethyl acetate 70:30); [a]D29
58.7 (c 1.32 in CHCl3); 1H NMR
(400 MHz, CDCl3, 258C, TMS): d 7.25 (d, J 8.5 Hz, 2H), 6.87 (d, J
8.5 Hz, 2H), 5.83 (ddt, J 17.1, 9.8, 7.3 Hz, 1H), 5.20 (brs, 1H), 5.12 (d, J
9.8 Hz, 1H), 5.11 (d, J 16.5 Hz, 1H), 4.46 (t, J 6.4 Hz, 1H), 4.42 (s, 2H),
3.80 (s, 3H), 3.70 (s, 3H), 3.42 (t, J 6.7 Hz, 2H), 3.44 ± 3.30 (brs, 1H), 3.33
(brs, 3H), 2.46 (dq, J 5.5, 7.3 Hz, 1H), 2.41 ± 2.15 (m, 4H), 2.08 ± 1.95 (m,
3H), 1.64 ± 1.53 (m, 2H), 1.49 ± 1.22 (m, 5H), 1.28 (d, J 7.3 Hz, 3H); IR
(film): nÄ 2945, 2860, 1775, 1710, 1612, 1515, 1423, 1375, 1310, 1245, 1197,
1170, 1085, 1030, 1003, 990, 947, 820 cm 1; MS (FAB): m/z (%): 514 (0.5)
1056, 1000, 775, 734 cm 1; MS (EI): m/z (%): 443 (20) [M] , 325 (23), 324
(87), 167 (22), 119 (34), 118 (72), 105 (100); HR-MS (EI): found: 443.1798
[M] ; C21H33O5NS2 calcd 443.1800; elemental analysis calcd (%)
for C21H33NO5S2 (443.6): C 56.86, H 7.50, N 3.16; found: C 56.58, H 7.44,
N 3.17.
Alcohol 36: A solution of dithiolane 35 (114 mg, 0.257 mmol) and Raney
nickel (W-2) (1.14 g) in ethanol (3.0 mL) was stirred and refluxed under a
nitrogen atmosphere for 2 h. After the solution had been cooled to room
temperature, the reaction mixture was filtered through a pad of Celite, and
the filtrates were concentrated in vacuo. The residue was purified by
column chromatography (chloroform/methanol 98:2 to 96:4) on silica gel to
[M H] , 484 (3.5) [M OMe] ; HR-MS (FAB): found: 484.2638 [M
OMe] ; C28H38O6N calcd 484.2699; elemental analysis calcd (%) for
C29H41NO7 (515.6): C 67.55, H 8.01, N 2.72; found: C 67.43, H 7.99, N 2.70.
Alcohol 33: Triethylsilane (0.415 mL, 2.60 mmol) and boron trifluoride
etherate (0.140 mL, 1.14 mmol) were added dropwise at 08C under a
nitrogen atmosphere to a solution of lactone 32 (268 mg, 0.520 mmol) in
acetonitrile (7.0 mL), and the solution was stirred at the same temperature
for 50 min. Saturated aqueous sodium hydrogen carbonate (15 mL) was
added, and the aqueous layer was extracted with dichloromethane (3 Â
afford alcohol 36 (77.4 mg, 85.2%) as a colorless oil: Rf 0.56 (chloroform/
1
methanol 90:10); [a]D27
122.2 (c 1.39 in CHCl3); H NMR (400 MHz,
CDCl3, 258C, TMS): d 4.51 ± 4.44 (brs, 1H), 3.89 ± 3.64 (m, 1H), 3.69 (s,
3H), 3.62 (t, J 6.1 Hz, 2H), 3.35 ± 3.22 (m, 1H), 3.25 (dt, J 5.8, 11.2 Hz,
1H), 2.72 ± 2.32 (m, 1H), 2.52 (dq, J 2.4, 7.5 Hz, 1H), 2.14 ± 2.00 (m, 1H),
4114
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0719-4114 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 19