H. Kamiyama et al. / Bioorg. Med. Chem. 19 (2011) 7541–7550
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warm to room temperature and stirred for an additional 9 h. The
147.1, 147.3, 148.5, 154.2; HRFABMS m/z calcd for C29H26NNa2O11S
mixture was quenched with water and the product was extracted
with dichloromethane. The extract was washed with water and
brine, dried over Na2SO4, and evaporated. The residue was purified
by column chromatography (hexane–ethyl acetate = 1:1) to give
19 as colorless solid (84.0 mg, 90%). Recrystallization from dichlo-
romethane–diethyl ether gave colorless needles. Mp 121.5–
[(M+Na)+] 642.1022, found 642.1015.
4.2.13. 8,9-Dihydro-3-Hydroxy-2,11,12-trimethoxy-14-[4-
methoxy-3-(methoxymethoxy)phenyl]-6H-
[1]benzopyrano[40,30:4,5]pyrrolo[2,1-a]isoquinolin-6-one (21)
According to the procedure described for the preparation of 18,
compound 16 (150 mg, 0.231 mmol) was hydrogenolyzed over pal-
ladium carbon (Pd: 10%, 30 mg) for 19 h. After chromatographic
purification (dichloromethane–ethyl acetate = 1:1), 21 was ob-
tained as colorless solid (127 mg, 98%). Recrystallization from
dichloromethane–diethyl ether gave colorless granules. Mp 225–
245 °C (dec) (sealed capillary); IR (KBr) 3107, 1664, 1415, 1273,
122.5 °C; IR (KBr) 1713, 1406, 1261 cmꢁ1 1H NMR (400 MHz,
;
CDCl3) d 3.11 (t, J = 7.1 Hz, 2H), 3.51 (s, 3H), 3.60 (s, 3H), 3.81 (s,
3H), 3.86 (s, 3H), 3.94 (s, 3H), 4.66 (t, J = 7.1 Hz, 2H), 4.94 (s, 2H),
5.23 (s, 2H), 6.65 (d, J = 1.8 Hz, 1H), 6.68 (dd, J = 1.8 and 8.1 Hz,
1H), 6.79 (d, J = 8.1 Hz, 1H), 6.82 (s, 1H), 6.98 (d, J = 8.3 Hz, 1H),
7.01 (dd, J = 1.7 and 8.3 Hz, 1H), 7.16 (d, J = 1.7 Hz, 1H), 7.23 (s,
1H), 7.46 (s, 1H); 13C NMR (100 MHz, CDCl3) d 37.8, 51.1, 55.8,
55.9, 56.0, 56.1, 56.4, 80.4, 92.4, 95.7, 106.4, 111.3, 111.8, 112.0,
112.4, 115.8, 118.3, 118.4, 119.9, 120.9, 123.9, 125.5, 126.2,
130.2, 132.0, 137.2, 144.7, 146.5, 147.4, 147.9, 149.0, 149.7,
154.6; HRFABMS m/z calcd for C33H32Cl3NO12S (M+) 771.0711,
found 771.0634.
1151 cmꢁ1 1H NMR (400 MHz, CDCl3) d 3.10 (t, J = 6.9 Hz, 2H),
;
3.38 (s, 3H), 3.46 (s, 3H), 3.50 (s, 3H), 3.89 (s, 3H), 3.95 (s, 3H),
4.67–4.76 (m, 1H), 4.78–4.87 (m, 1H), 5.20 (d, J = 6.7 Hz, 1H),
5.23 (d, J = 6.7 Hz, 1H), 5.81 (s, 1H), 6.63 (s, 1H), 6.68 (s, 1H), 6.75
(s, 1H), 6.94 (s, 1H), 7.10 (d, J = 8.2 Hz, 1H), 7.16 (dd, J = 1.9 and
8.2 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) d
28.7, 42.4, 55.1, 55.6, 56.0, 56.3, 56.3, 95.8, 103.4, 104.2, 108.8,
110.3, 111.1, 112.7, 113.7, 114.4, 120.0, 120.1, 125.6, 126.7,
128.3, 128.3, 136.0, 143.4, 145.6, 146.5, 147.1, 147.5, 149.0,
150.0, 155.6. Anal. Calcd for C31H29NO9: C, 66.54; H, 5.22; N,
2.50. Found: C, 66.48; H, 4.99; N, 2.49.
4.2.11. 3-[2-(3,4-Dimethoxyphenyl)ethyl]-3,4-dihydro-1-(3-
hydroxy-4-methoxyphenyl)-8-methoxy-4-oxo-
[1]benzopyrano[3,4-b]pyrrol-7-yl 2,2,2-trichloroethyl sulfate
(20)
To a mixture of 19 (107 mg, 0.139 mmol), dichloromethane
(12 mL), and methanol (6.0 mL) was added concd HCl (1.0 mL).
The mixture was stirred for 12 h at 30 °C, and evaporated. The pre-
cipitate thus formed was collected by filtration, washed with
water, and dried under reduced pressure to give 20 as pale brown
solid (95.1 mg, 94%). Recrystallization from methanol–water gave
pale brown granules. Mp 75–105 °C (dec) (sealed capillary); IR
4.2.14. 8,9-Dihydro-2,11,12-trimethoxy-14-[4-methoxy-3-
(methoxymethoxy)phenyl]-6-oxo-6H-
[1]benzopyrano[40,30:4,5]pyrrolo[2,1-a]isoquinolin-3-yl 2,2,2-
trichloroethyl sulfate (22)
According to the procedure described for the preparation of 19,
compound 21 (85.0 mg, 0.152 mmol) was reacted with 2,2,2-tri-
chloroethyl chlorosulfate (49.0 mg, 0.197 mmol). After chromato-
graphic purification (dichloromethane–ethyl acetate = 20:1), 22
was obtained as colorless solid (116 mg, 99%). Recrystallization
from dichloromethane–diethyl ether gave colorless needles. Mp
125–155 °C (dec) (sealed capillary); IR (KBr) 1718, 1487, 1414,
(KBr) 3423, 1719, 1413, 1263 cmꢁ1 1H NMR (400 MHz, DMSO-
;
d6) d 3.03 (t, J = 6.9 Hz, 2H), 3.58 (s, 3H), 3.67 (s, 3H), 3.71 (s, 3H),
3.82 (s, 3H), 4.63 (t, J = 6.9 Hz, 2H), 5.35 (s, 2H), 6.65 (dd, J = 1.7
and 8.2 Hz, 1H), 6.74 (d, J = 1.7 Hz, 1H), 6.82 (dd, J = 2.1 and
8.2 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 2.1 Hz, 1H), 7.05
(d, J = 8.2 Hz, 1H), 7.36 (s, 1H), 7.41 (s, 1H), 7.67 (s, 1H), 9.35 (s,
1H); 13C NMR (100 MHz, DMSO-d6) d 36.7, 49.7, 55.2, 55.4, 55.7,
55.7, 80.0, 92.8, 106.0, 111.7, 111.9, 112.4, 112.4, 115.1, 116.6,
118.1, 119.7, 120.4, 120.7, 124.0, 125.6, 130.1, 132.8, 136.2,
143.7, 146.5, 147.0, 147.3, 147.4, 148.4, 153.6; HRFABMS m/z calcd
for C31H29Cl3NO11S [(M+H)+] 728.0527, found 728.0543.
1199 cmꢁ1 1H NMR (400 MHz, CDCl3) d 3.13 (t, J = 6.9 Hz, 2H),
;
3.39 (s, 3H), 3.46 (s, 3H), 3.49 (s, 3H), 3.90 (s, 3H), 3.96 (s, 3H),
4.70–4.79 (m, 1H), 4.80–4.89 (m, 1H), 4.92 (s, 2H), 5.21 (d,
J = 6.8 Hz, 1H), 5.23 (d, J = 6.8 Hz, 1H), 6.68 (s, 1H), 6.77 (s, 1H),
6.81 (s, 1H), 7.11 (d, J = 8.2 Hz, 1H), 7.16 (dd, J = 1.9 and 8.2 Hz,
1H), 7.31 (d, J = 1.9 Hz, 1H), 7.42 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 28.6, 42.6, 55.1, 55.6, 56.0, 56.0, 56.3, 80.4, 92.5, 95.7, 106.2,
108.7, 111.1, 112.3, 112.7, 114.6, 115.3, 118.3, 119.7, 119.7,
125.4, 126.6, 126.7, 127.6, 136.4, 137.1, 144.7, 147.3, 147.3,
147.6, 149.3, 150.2, 154.7. Anal. Calcd for C33H30Cl3NO12S: C,
51.41; H, 3.92; N, 1.82. Found: C, 51.70; H, 3.77; N, 1.71.
4.2.12. Sodium 3-[2-(3,4-dimethoxyphenyl)ethyl]-3,4-dihydro-
1-(3-hydroxy-4-methoxyphenyl)-8-methoxy-4-oxo-
[1]benzopyrano[3,4-b]pyrrol-7-yl sulfate (2)
Under an argon atmosphere,
a mixture of 20 (50.0 mg,
0.0686 mmol), ammonium formate (25.9 mg, 0.411 mmol), zinc
(powder, 13.5 mg, 0.206 mmol), methanol (20 mL), and THF
(20 mL) was stirred for 15 h at room temperature and passed
through a pad of Celite. The filtrate was evaporated and the residue
was purified successively by column chromatography over Silica
Gel 60 N (ethyl acetate–methanol = 3:1), column chromatography
over Amberlite IRC-50 (Na+ form) (ethyl acetate–methanol–
water = 1:1:1), and column chromatography over Sephadex LH-
20 (ethyl acetate–methanol = 1:1) to give 2 as pale yellow powder
(38.1 mg, 90%). Mp 170–230 °C (dec) (sealed capillary); IR (KBr)
4.2.15. 8,9-Dihydro-14-(3-hydroxy-4-methoxyphenyl)-2,11,12-
trimethoxy-6-oxo-6H-[1]benzopyrano[40,30:4,5]pyrrolo[2,1-
a]isoquinolin-3-yl 2,2,2-trichloroethyl sulfate (23)
According to the procedure described for the preparation of 20,
compound 22 (48.3 mg, 0.0626 mmol) was treated with concd HCl
(0.8 mL) in a mixture of dichloromethane (10 mL) and methanol
(5 mL) for 20 h to give 23 as colorless solid (42.1 mg, 92%). Recrys-
tallization from acetone–hexane gave colorless powder. Mp 230–
240 °C (dec) (sealed capillary); IR (KBr) 3360, 1713, 1413,
3424, 1705, 1260, 1049 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6) d
1213 cmꢁ1 1H NMR (400 MHz, DMSO-d6) d 3.12 (t, J = 6.7 Hz,
;
3.03 (t, J = 7.2 Hz, 2H), 3.50 (s, 3H), 3.67 (s, 3H), 3.71 (s, 3H), 3.81
(s, 3H), 4.61 (t, J = 7.2 Hz, 2H), 6.68 (dd, J = 1.9 and 8.2 Hz, 1H),
6.74 (d, J = 1.9 Hz, 1H), 6.79 (dd, J = 2.1 and 8.2 Hz, 1H), 6.85 (d,
J = 8.2 Hz, 1H), 6.91 (d, J = 2.1 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H),
7.22 (s, 1H), 7.32 (s, 1H), 7.51 (s, 1H), 9.39 (br s, 1H); 13C NMR
(100 MHz, DMSO-d6) d 36.7, 49.6, 55.2, 55.3, 55.4, 55.6, 105.1,
108.8, 111.7, 112.2, 112.3, 112.4, 114.4, 116.7, 118.8, 120.1,
120.6, 125.3, 126.1, 130.3, 132.5, 142.2, 144.4, 146.5, 146.6,
2H), 3.27 (s, 3H), 3.43 (s, 3H), 3.78 (s, 3H), 3.84 (s, 3H), 4.56–4.65
(m, 1H), 4.66–4.75 (m, 1H), 5.35 (s, 2H), 6.71 (s, 1H), 6.90–6.95
(m, 3H), 7.00 (s, 1H), 7.18 (d, J = 8.6 Hz, 1H), 7.69 (s, 1H), 9.42 (s,
1H); 13C NMR (100 MHz, DMSO-d6) d 27.4, 54.4, 55.4, 55.5, 55.9,
80.0, 92.8, 105.8, 108.5, 111.6, 111.9, 113.4, 113.7, 115.4, 117.5,
117.8, 118.8, 121.4, 125.3, 126.3, 126.9, 135.6, 136.2, 143.8,
146.9, 147.0, 147.6, 147.8, 149.0, 153.4; HRFABMS m/z calcd for
C
31H27Cl3NO11S [(M+H)+] 726.0370, found 726.0374.