M. Ito et al. / Tetrahedron 67 (2011) 8041e8049
8047
After addition of CHCl3 (15 mL), the mixture was successively
washed with H2O, 1 N NaOH, H2O, and brine, dried (Na2SO4), and
evaporated. Purification of the residue by SiO2 column chroma-
tography (hexane/AcOEt¼4:1) gave (ꢁ)-11,12-dehydro-10b-
hydroxylactam (ꢁ)-20 (7 mg, 21%) and oxysanguinarine (21) (4 mg,
11%) as colorless solids, respectively. (i) (ꢁ)-10b-Hydroxy-5-methyl-
2,3; 7,8-bis(methylenedioxy)-4b,10b-dihydrobenzo[c]phenanthridin-
6(5H)-one [(ꢁ)-20]. Mp: 257e260 ꢂC. IR nmax cmꢁ1: 3342 (OH),1639
benzoate (ꢁ)-25 (16 mg, 57%) as colorless solids. Mp: 181e183 ꢂC.
IR nmax cmꢁ1: 3377 (OH), 1712 (C]O), 1635 (C]O). 1H NMR
(400 MHz):
d (ppm) 3.42 (s, 1H), 3.52 (s, 3H), 5.02 (s, 1H), 5.11 (d,
J¼3.1 Hz, 1H), 5.49 (s, 1H), 5.84 (d, J¼1.1 Hz, 1H), 5.88 (d, J¼1.1 Hz,
1H), 5.91 (d, J¼1.1 Hz, 1H), 5.92 (d, J¼1.1 Hz, 1H), 6.10 (d, J¼3.1 Hz,
1H), 6.62 (s, 1H), 6.67 (s, 1H), 6.80 (d, J¼8.1 Hz, 1H), 7.11 (d, J¼8.1 Hz,
1H), 7.43 (dd, J¼7.9, 7.9 Hz, 1H), 7.58 (br d, J¼7.9 Hz, 1H), 8.03 (br d,
J¼7.9 Hz, 1H), 8.11 (t, J¼1.8 Hz, 1H). 13C NMR (100 MHz):
d (ppm)
(C]O). 1H NMR (400 MHz):
d
(ppm) 3.42 (s, 3H), 4.80 (s, 2H),
38.0, 64.9, 70.7, 71.4, 72.5, 101.5, 102.3, 105.4, 107.5, 111.2, 111.8,
117.2, 124.4, 128.0, 129.9, 129.9, 130.7, 131.3, 133.6, 134.8, 147.7,
148.6, 149.1, 161.9, 165.4. HRFABMS m/z: 538.0895 (calcd for
5.84e5.87 (m, 4H), 6.33 (d, J¼9.9 Hz, 1H), 6.40 (d, J¼9.9 Hz, 1H),
6.51 (s, 1H), 6.57 (s, 1H), 6.67 (d, J¼7.8 Hz, 1H), 6.80 (d, J¼7.8 Hz,1H).
13C NMR (100 MHz):
d
(ppm) 36.4, 69.6, 70.6, 101.2, 102.2, 105.5,
C27H2135ClNO9: 538.0905). ½a 2D4
ꢁ59 (c 0.087, CHCl3).
ꢄ
107.4, 110.6, 112.1, 117.5, 126.8, 127.4, 128.8, 131.7, 133.4, 147.0, 147.1,
147.3, 148.8, 161.7. HRFABMS m/z: 366.0994 (calcd for C20H15NO6:
3.1.13. (ꢁ)-12-(3-Chlorobenzoyloxy)-11-hydroxy-5-methyl-2,3; 7,8-
bis(methylenedioxy)-10b-triethylsilyloxy-4b,5,6,10b,11,12-
hexahydrobenzo[c]phenanthridin-6(5H)-one [(ꢁ)-26]. A solution of
366.0978). ½a 2D4
ꢁ10 (c 0.107, CHCl3). (ii) 5-Methyl-2,3; 7,8-bis(me-
ꢄ
thylenedioxy)benzo[c]phenanthridin-6(5H)-one (oxysanguinarine)
(21). Mp: >300 ꢂC (lit.27 Mp 360e362 ꢂC). IR nmax cmꢁ1: 1649 (C]
(ꢁ)-11,12-dehydro-10b-silyloxylactam
(ꢁ)-22
(328 mg,
O). 1H NMR (400 MHz):
d
(ppm) 3.91 (s, 3H) 6.10 (s, 2H), 6.27 (s, 2H),
0.683 mmol) and mCPBA (227 mg, 0.987 mmol) in CH2Cl2 (18 mL)
was stirred at 0 ꢂC for 2 h and at rt for 25 h, diluted with H2O
(10 mL), and extracted with CH2Cl2 (30 mLꢃ3). The organic solu-
tions were washed with satd NaHCO3 aq and brine, dried (MgSO4),
and evaporated. Purification of the residue by SiO2 column chro-
matography (hexane/AcOEt¼4:1 to 2:1) gave (ꢁ)-11-hydroxy-10b-
silyloxylactam 12-benzoate (ꢁ)-26 (312 mg, 70%) as colorless
solids. Mp: 145e148 ꢂC. IR nmax cmꢁ1: 3387 (OH), 1714 (C]O), 1648
7.16 (s, 1H), 7.24 (d, J¼8.6 Hz, 1H), 7.53 (d, J¼8.8 Hz, 1H), 7.57 (s, 1H),
7.76 (d, J¼8.6 Hz, 1H), 7.98 (d, J¼8.8 Hz, 1H). 13C NMR (100 MHz):
d
(ppm) 40.8,101.5,102.5,102.9,104.7,110.9,113.2,115.4,117.3,118.7,
121.1, 123.5, 131.8, 135.6, 147.1, 147.5, 147.7, 147.8, 162.7. LREIMS m/z:
347 (Mþ).
3.1.11. DDQ oxidation of (ꢁ)-10b-silyloxylactam (ꢁ)-17. A mixture
of (ꢁ)-10b-silyloxylactam (ꢁ)-17 (521 mg, 1.08 mmol), K2CO3
(403 mg, 2.91 mmol), and DDQ (411 mg, 1.81 mmol) in benzene
(20 mL) was refluxed for 7 h under argon and the separated ppt was
filtered off through a Celite pad. After evaporation of the filtrate, the
residue was successively purified by Al2O3 column chromatography
(toluene/acetone¼30:1) and SiO2 column chromatography (hex-
ane/AcOEt¼4:1 to 1:1) to afford (ꢁ)-11,12-dehydro-10b-silylox-
ylactam (ꢁ)-22 (518 mg, 63%) as colorless solids and
(þ)-spiroindenyloxoisoquinolone (þ)-23 (125 mg, 32%) as yellow
solids. (i) (ꢁ)-5-Methyl-2,3;7,8-bis(methylenedioxy)-10b-triethylsi-
(C]O). 1H NMR (400 MHz):
d (ppm) 0.29e0.42 (m, 6H), 0.84 (t,
J¼8.0 Hz, 9H), 2.87 (s, 1H), 3.49 (s, 3H), 4.89 (s, 1H), 5.06 (d,
J¼3.8 Hz, 1H), 5.89 (s, 1H), 5.92 (s, 1H), 6.01 (s, 1H), 6.13 (d, J¼3.8 Hz,
1H), 6.20 (s,1H), 6.66 (s, 2H), 6.92 (d, J¼8.1 Hz,1H), 7.16 (d, J¼8.1 Hz,
1H), 7.44 (t, J¼8.2 Hz, 1H), 7.59 (d, J¼8.2 Hz, 1H), 8.04 (d, J¼8.2 Hz,
1H), 8.12 (s, 1H). 13C NMR (100 MHz):
d (ppm) 5.67, 6.89, 38.1, 65.4,
71.2, 72.4, 74.3, 101.5, 102.6, 105.7, 107.3, 110.7, 113.5, 118.6, 124.0,
128.0, 129.1, 129.3, 129.87, 129.91, 131.3, 133.6, 134.8, 147.8, 148.3,
148.6, 150.0, 161.5, 165.4. HRFABMS m/z: 652.1750 (calcd for
C33H3535ClNO9Si: 652.1770). ½a 2D4
ꢁ74 (c 0.127, CHCl3). Evaporation
ꢄ
lyloxy-4b,10b-dihydrobenzo[c]phenanthridin-6(5H)-one
[(ꢁ)-22]:
of mother liquor in the recrystallization of the above solids from
Mp: 78e79.5 ꢂC. IR nmax cmꢁ1: 1652 (C]O). 1H NMR (400 MHz):
hexane/AcOEt afforded optically pure crystals. Mp: 135.5e138 ꢂC.
d
(ppm) 0.39 (q, J¼7.8 Hz, 6H) 0.85 (t, J¼7.8 Hz, 9H), 3.37 (s, 3H),
½
a 2D0
ꢄ
ꢁ83 (c 0.308, CHCl3) (98% ee).
4.71 (s,1H), 5.86 (s,1H), 5.87 (s,1H), 6.00 (s,1H), 6.16 (s,1H), 6.25 (d,
J¼9.9 Hz, 1H), 6.37 (d, J¼9.9 Hz, 1H), 6.50 (s, 1H), 6.61 (s, 1H), 6.71
(d, J¼8.1 Hz, 1H), 6.78 (d, J¼8.1 Hz, 1H). 13C NMR (100 MHz):
3.1.14. 11,12-Isopropylidenedioxy-10b-methoxy-5-methyl-2,3; 7,8-
bis(methylenedioxy)-4b,10b,11,12-tetrahydrobenzo[c]phenanthridin-
6(5H)-one (31). A solution of the acetal mixture 29 (23 mg,
0.05 mmol), SOCl2 (0.008 mL, 0.110 mmol), and Et3N (0.05 mL,
0.36 mmol) in CH2Cl2 (1 mL) was stirred at 0 ꢂC for 2 h under argon.
After evaporation the residue was dissolved in MeOH (3 mL), stir-
red at rt for 2 days under argon, and evaporated. The residue was
dissolved in CHCl3 (30 mL), washed with H2O and brine, dried
(MgSO4), and evaporated. Purification of the residue by SiO2 col-
umn chromatography (hexane/AcOEt¼2:1 to 1:2) gave 10b-
methoxylactam 11,12-acetal 31 (12 mg, 50%) as pale brown solids.
Mp: 116e120.5 ꢂC. IR nmax cmꢁ1: 1648 (C]O). 1H NMR (400 MHz):
d
(ppm) 5.93, 6.87, 36.4, 70.1, 72.9, 101.2, 102.3, 105.8, 107.3, 110.0,
113.5, 118.1, 126.5, 127.1, 129.1, 131.8, 132.8, 146.9, 147.3, 147.3, 149.3,
161.6. HRFABMS m/z: 480.1850 (calcd for C26H30NO6Si: 480.1842).
½
a 2D4
ꢄ
ꢁ36 (c 0.188, CHCl3). (ii) (þ)-Spiro[2,3-dihydro-2-methyl-7,8-
methylenedioxy-2H-isoquinoline-1,4-dione-3,10-50,60-methylenediox-
yindene] [(þ)-23]: mp: 147e150 ꢂC. IR nmax cmꢁ1: 1697 (C]O). 1H
NMR (400 MHz):
d
(ppm) 2.85 (s, 3H), 5.99 (d, J¼1.2 Hz,1H), 6.03 (d,
J¼1.2 Hz, 1H), 6.11 (d, J¼1.2 Hz, 1H), 6.14 (d, J¼1.2 Hz, 1H), 6.18 (d,
J¼10.1 Hz, 1H), 6.52 (s, 1H), 6.57 (d, J¼8.0 Hz, 1H), 6.76 (d, J¼8.0 Hz,
1H), 6.89 (s, 1H), 7.48 (d, J¼10.1 Hz, 1H). 13C NMR (100 MHz):
d
(ppm) 26.8, 75.8, 102.1, 103.0, 107.1, 109.8, 111.1, 112.7, 113.9, 123.0,
d (ppm) 1.26 (s, 3H), 1.53 (s, 3H), 3.15 (s, 3H), 3.47 (s, 3H), 4.79 (s,
124.6, 134.4, 137.2, 143.7, 146.1, 148.3, 149.3, 150.6, 167.3, 194.3.
1H), 5.08 (d, J¼5.7 Hz, 1H), 5.26 (d, J¼5.7 Hz, 1H), 5.89 (s, 1H), 5.89
HRFABMS m/z: 364.0835 (calcd for C20H14NO6: 364.0821). ½a D20
ꢄ
(s, 1H), 6.00 (s, 1H), 6.13 (s, 1H), 6.59 (s, 1H), 6.66 (s, 1H), 6.74 (d,
þ121 (c 0.126, CHCl3).
J¼8.4 Hz, 1H)., 6.77 (d, J¼8.4 Hz, 1H). 13C NMR (100 MHz):
d (ppm)
26.5, 27.5, 37.4, 50.5, 62.7, 72.3, 75.6, 76.2, 101.3, 102.6, 105.1, 108.7,
109.3, 110.0, 113.0, 118.1, 127.4, 127.5, 128.5, 147.6, 148.3, 148.6, 149.8,
161.5. HRESIMS m/z: 476.13466 (calcd for C24H23NNaO8: 476.13214).
3.1.12. (ꢁ)-12-(3-Chlorobenzoyloxy)-10b,11-dihydroxy-5-methyl-
2,3;
7,8-bis(methylenedioxy)-4b,5,6,10b,11,12-hexahydrobenzo[c]
phenanthridin-6(5H)-one [(ꢁ)-25]. To
a
solution of (ꢁ)-11,12-
dehydro-10b-hydroxylactam (ꢁ)-20 (19 mg, 0.052 mmol) in
CH2Cl2 (1 mL) was added mCPBA (9 mg, 0.055 mmol) at 0 ꢂC under
argon, and the whole was stirred at 0 ꢂC for 2 h and at rt for 16 h.
After dilution with CH2Cl2 (5 mL) and H2O (2 mL), the separated
organic layers were washed with brine, dried (Na2SO4), and evap-
orated. Purification of the residue by SiO2 column chromatography
(hexane/AcOEt¼4:1 to 3:2) gave (ꢁ)-10b,11-dihydroxylactam 12-
3.1.15. (ꢁ)-11,12-Isopropylidenedioxy-5-methyl-2,3; 7,8-bis
(methylenedioxy)-4b,5,6,10b,11,12-hexahydrobenzo[c]phenanthridine
[(ꢁ)-34]. A mixture of (þ)-4b,10-dehydrolactam 11,12-acetal 27
(21 mg, 0.05 mmol) and LAH (12 mg, 0.32 mmol) in Et2O (3 mL)
was refluxed for 1 h, quenched by addition of 10% NaOH aq (1 mL),
and extracted with AcOEt (15 mLꢃ3) after addition of H2O (10 mL).
The organic solutions were washed with satd NH4Cl aq and brine,