762
HETEROCYCLES, Vol. 79, 2009
chromatography with CHCl3:MeOH (200:1, v/v) as an eluent gave the isocoumarin 18 (403.1 mg, 59%)
1
as colorless oil. IR (neat) cm-1: 1732, 1602, 1152. H NMR δ: 0.88-0.92 (3H, m), 1.32-1.36 (4H, m),
1.64-1.71 (2H, m), 3.45 (2H, t, J=7.6 Hz), 3.49 (3H, s), 3.55 (3H, s), 5.23 (2H, s), 5.34 (2H, s), 6.09 (1H,
13
s), 6.58 (1H, d, J=2.3 Hz), 6.79 (1H, d, J=2.3 Hz). C NMR δ: 13.9, 22.4, 26.4, 31.1, 33.2, 56.4, 56.5,
94.1, 95.1, 102.9, 103.48, 103.50, 104.6, 142.0, 159.0, 159.3, 160.7, 162.6. MS (CI) m/z 337 (M++1):
HRMS Calcd for C18H25O6 (M++1): 337.1651, Found: 337.1629.
6,8-Bis(methoxymethoxy)-3-pentyl-2H-isoquinolin-1-one (19). Isocoumarin 18 (302.2 mg, 0.90 mmol)
was dissolved in DMF (7 mL) in a round bottom flask. To the solution was added NH4OH (25-28%
solution in water, 7 mL), and then the flask was sealed with rubber septum. The mixture was stirred at rt
for 60 h. After removing the septum, the mixture was stirred at 90-100 °C for 2 h. The solvent was
removed by distillation under reduced pressure to give crude product. Column chromatography of the
crude product with CHCl3:MeOH (30:1, v/v) as an eluent gave the isocarbostyril 19 (266.8 mg, 89%) as
1
white prisms (recrystallized from methanol), mp 93-95 °C. IR (neat) cm-1: 3171, 1646, 1605, 1152. H
NMR δ: 0.87-0.91 (3H, m), 1.32-1.38 (4H, m), 1.67-1.75 (2H, m), 2.55 (2H, t, J=7.6 Hz), 3.50 (3H, s),
3.58 (3H, s), 5.24 (2H, s), 5.33 (2H, s), 6.14 (1H, s), 6.72 (1H, d, J=2.3 Hz), 6.75 (1H, d, J=2.3 Hz), 10.52
(1H, s). 13C NMR δ: 13.9, 22.4, 27.6, 31.2, 32.9, 56.3, 56.4, 94.1, 95.9, 103.6, 103.7, 103.9, 110.4, 142.8,
143.1, 159.7, 166.6, 162.7. MS (CI) m/z 336 (M++1). HRMS Calcd for C18H26NO5 (M++1): 336.1811,
Found: 336.1807. Anal Calcd for C18H25NO5: C 64.46, H 7.51, N 4.18; Found: C 64.29, H 7.44, N 4.09.
6,8-Dihydroxy-3-pentyl-2H-isoquinolin-1-one (20). Compound 19 (232.6 mg, 0.69 mmol) was
dissolved in a MeOH (5 mL). To the solution was added 6 drops of concentrated HCl, and the resulting
mixture was stirred at 50 °C for 24 h. The solvent was evaporated in reduced pressure. The residue was
purified by column chromatography with CHCl3:MeOH (30:1, v/v) as an eluent to give the diol 20 (165.0
mg, 80%) as white needles (recrystallized from MeOH), mp 170-172 °C. IR (neat) cm-1: 3297, 3168,
3067, 1653. 1H NMR δ: 0.92 (3H, t, J=6.8 Hz), 1.35-1.38 (4H, m), 1.64-1.71 (2H, m), 2.50 (2H, t, J=7.6
Hz), 6.21 (1H, s), 6.28 (1H, d, J=2.1 Hz), 6.33 (1H, d, J=2.1 Hz). 13C NMR δ: 13.0, 21.8, 27.5, 30.6, 32.3,
99.6, 100.4, 103.8, 104.5, 140.9, 131.1, 162.1, 162.5, 166.1. MS (CI) m/z 228 (M++1). HRMS Calcd for
C14H18NO3 (M++1):248.1286, Found: 248.1293.
Ruprechstyril (3) and O-methylruprechstyril (21). Compound 20 (102.8 mg, 0.42 mmol) was
dissolved in acetone (8 mL). To the solution were added iodomethane (25.9 µL, 0.42 mmol) and cesium
carbonate (135.5 mg, 0.42 mmol). The resulting mixture was stirred at rt for 23 h. The solvent was
evaporated in reduced pressure. To the residue were added saturated aqueous NH4Cl solution and a
mixture of CHCl3:MeOH (10:1, v/v). After separation, the aqueous layer was extracted three times with
CHCl3:MeOH (10:1, v/v). The organic layers were combined, washed with brine, dried over Na2SO4, and