1
268
M. Hirnschall, K. Mereiter, J. Froehlich and U. Jordis
Vol. 39
1H); 13C NMR (CDCl ): d 197.9 (s), 152.6 (d), 145.2 (s), 142.4
(s), 127.8 (d), 127.7 (s), 126.5 (s), 117.3 (d), 109.2 (d), 69.2 (d),
61.0 (t), 56.0 (q), 53.6 (t), 45.8 (s), 42.9 (t), 40.2 (t).
Synergi Polar-RP 4µ (4.6 x 150 mm) column, a 600-MS pump
Waters), a 712 WISP autosampler (Waters) and a 996 photodi-
ode array detector (Waters).
3
(
Anal. Calcd for C H NO •0.25H O: C, 69.67; H, 6.39; N,
.08. Found: C, 69.63; H, 6.56; N, 4.89.
16
17
3
2
(
6
4aR*,8aR*)-1-Bromo-4a,5,9,10,11,12-hexahydro-3-methoxy-
H-benzofuro[3a,3,2-ef][2]benzazepin-6-one, Bromnorn-
arwedine (10) was prepared as previously described [3].
5
Compound 12 was obtained as colorless crystals 0.12 g (9.3 %
1
yield), mp 196-199 °C; H NMR (CDCl ): d 7.93 (d, J = 9.8 Hz,
3
(
4aS*,8aS*)-4a,5,9,10,11,12-Hexahydro-3-methoxy-6H-benzo-
1H), 6.69 (d, J = 8.1 Hz, 1H), 6.49 (d, J = 8.1 Hz, 1H), 5.93 (d, J
= 9.80 Hz, 1H), 4.21 (d, J = 17.3 Hz, 1H), 3.81 (s, 3H), 3.66 (d, J
furo[3a,3,2-ef][2]benzazepin-6-one (-)-Nornarwedine (9).
=
17.3 Hz, 1H), 3.42 (dt, J = 11.4 Hz, 3.1 Hz, 1H), 3.15 (dd, J =
To a solution of (-)-narwedine, 7 (5.00 g, 17.5 mmol) in CH C l2
50 mL) m-CPBA (peroxide content 75% by titration, 3.18 g, 18.4
mmol) was added and the clear solution stirred 1.5 h at ambient
temperature. At this stage the conversion to the N-oxide is quanti-
2
1
2
1
1
3
4.0 Hz, 4.1 Hz, 1H), 2.98-2.71 (m, 1H), 2.69-2.21 (m, 3H),
(
.06-1.83 (m, 1H); 13C NMR (CDCl ): d 198.7 (s), 155.0 (d),
3
46.0 (s), 143.0 (s), 127.6 (d), 126.3 (s), 124.7 (s), 116.6 (d),
09.4 (d), 64.9 (d), 56.0 (q), 54.4 (t), 53.3 (t), 43.6 (s), 40.1 (t),
8.5 (t).
tative as determined by HPLC. Then a solution of FeSO • 7 HO
4
2
(
2.44 g, 8.76 mmol) in MeOH (20 mL) was added. The mixture
Anal. Calcd for C H NO •0.33H O: C, 69.31; H, 6.42; N,
was stirred for 20 min., treated with Na H P O• 1 2 HO (4.00 g,
16 17
3
2
2
4
2
5
.05. Found: C, 69.02; H, 6.26; N, 4.97.
1
1.2 mmol) in water (20 mL) and stirred for 5 min. The precipitate
was collected by filtration, washed with CH C l (2 x 40 mL). The
biphasic mixture was adjusted to pH > 8.5 with conc. ammonia,
2
2
rel-(4aS,5R,10bR)-1-Bromo-4,4a-dihydro-10-hydroxy-9-
methoxy-3H,6H-5,10b-ethanophenanthridin-3-one, = rel-
(4aS,5R,10bR)-1-Bromo-10,11-seco-powellamin-3-one (13) and
rel-(4aR,5R,10bR)-1-Bromo-4,4a-dihydro-10-hydroxy-9-
methoxy-3H,6H-5,10b-ethanophenanthridin-3-one, = rel-
separated and the aqueous phase was extracted with CH C l (2 x
2
2
5
0 mL). The combined organic layers were washed with 0.25 N
NaOH (1 x 50 mL), and brine (1 x 50 mL), dried (Na S O) and
2
4
filtered. After concentration in vacuothe residue was dissolved in
MeOH (30 mL) and treated with a solution of oxalic acid dihy-
drate (3.31 g, 26.3 mmol) in MeOH (30 mL). The precipitate of
(
4aR,5R,10bR)-1-Bromo-10,11-seco-isopowellamin-3-one (14).
Compound 10 (2.66 g, 7.60 mmol) and CaCl (1.26 g, 11.4
2
mmol) in 70 % ethanol (100 mL) were stirred under reflux for
70 h. The mixture was concentrated in vacuo, and the residue
9
• CH O was collected by filtration and washed with MeOH (2 x
2 2 4
1
10 mL). Yield: colorless crystals, 3.25 g (51%), mp. 200 – 203 °C
was partitioned between 2 N HCl (100 mL) and EtOAc (100 mL).
The aqueous layer was basified with conc. ammonia and
extracted with CH2Cl2 (3 x 100 mL). The combined organic lay-
ers were washed with brine (1 x 50 mL), dried (Na SO ) and fil-
(
decomp.). Treatment of 9• C H O with ammonia and extractive
2
2 4
workup yielded the free base: colorless crystals, 2.38 g (50%),
1
mp. 168 – 170 °C; H NMR (CDCl ): d 6.91 (dd, J = 10.4 Hz, 1.9
3
Hz, 1H), 6.73–6. 56 (m, 2H), 6.00 (d, J = 10.4 Hz, 1H), 4.75-4.66
2
4
tered. After concentration in vacuo, the residue was purified by
(
m, 1H), 3.99 (s, 2H), 3.80 (s, 3H), 3.42 (dt, J = 14.7 Hz, 3.5 Hz,
flash chromatography (SiO , CHCl :MeOH:NH = 95:4:1).
1
1
H), 3.21-3.08 (m, 1H), 2.72 (dd, J = 17.8 Hz, 3.7 Hz, 1H), 2.19-
2
3
3
1
1
3
Yield: 13: colorless crystals, 0.74 g, (28%), mp 241 – 244 °C, H
NMR (DMSO-d +10% TFA-d ): d 8.65 (d, J = 10.5 Hz, 1H),
.80 (m, 4H); C NMR (CDCl ): d 194.3 (s), 144.6 (d), 143.8
3
(
8
s), 133.3 (s), 130.6 (s), 127.7 (s), 127.0 (d), 120.6 (d), 111.7 (d),
7.8 (d), 56.0 (q), 53.9 (t), 49.5 (s), 47.3 (t), 39.7 (t), 37.2 (t).
Anal. Calcd for C16H17NO : C, 70.83; H, 6.32; N, 5.16.
6
1
8
4
3
2
.00 (s, 1H), 6.01 (d, J = 10.5 Hz, 1H), 4.64 (d, J = 15.5 Hz, 1H),
.39-4.31 (m, 1H), 4.26 (d, J = 15.5 Hz, 1H), 4.21 – 4.08 (m, 1H),
.83 (s, 3H), 3.56 – 3.34 (m, 1H), 2.98 – 2.79 (m, 2H), 2.65 –
.42 (m, 2H); 13C NMR (DMSO-d +10% TFA-d ): d 192.7 (s),
3
Found: C, 70.62; H, 6.42; N, 4.99.
6
1
rel-(4aS,5R,10bR)-4,4a-Dihydro-10-hydroxy-9-methoxy-3H,6H-
148.5 (s), 147.4 (d), 143.7 (s), 129.1 (d), 126.7 (s), 118.4 (s),
115.0 (d), 111.0 (s), 67.0 (d), 58.9 (t), 56.5 (q), 52.9 (t), 46.5 (s),
39.3 (t), 36.5 (t).
5
,10b-ethanophenanthridin-3-one, = rel-(4aS,5R,10bR)-10,11-
Seco-powellamin-3-one (11) and rel-(4aR,5R,10bR)-4,4a-
Dihydro-10-hydroxy-9-methoxy-3H,6H-5,10b-ethanophenan-
thridin-3-one, = rel-(4aR,5R,10bR)-10,11-Seco-isopowellamin-
Anal. Calcd for C H NO Br•0.33 H O: C, 53.95; H, 4.72;
16
16
3
2
N, 3.93. Found: C, 54.01; H, 4.61; N, 3.85. For X-ray work 13
3
-one (12).
was transformed to the hydrochloride and crystallized from water
as 13•HCl•H O.
Compouind 14 was obtained as colorless crystals, 0.60 g (23%
yield), mp 219 – 224 °C, Identical H and C NMR as previ-
ously reported [3].
Anal. Calcd for C H NO Br•0.33 H O: C, 53.95; H, 4.72;
N, 3.93. Found: C, 53.98; H, 4.53; N, 3.78.
X-Ray Structure Determinations of 11, 12, 13, and 14.
General.
Compound 9 (1.30 g, 4.79 mmol) and CaCl2 (0.80 g, 7.19
2
mmol) in 70 % ethanol (50 mL) were stirred under reflux for 160
h and the reaction progress followed by HPLC (Figures 1 and 2).
The mixture was concentrated in vacuo, and the residue was par-
titioned between 2 N HCl (50 mL) and EtOAc (50 mL). The
aqueous layer was basified with conc. ammonia and extracted
1
13
16 16
3
2
with CH Cl (3 x 50 mL). The combined organic layers were
2
2
washed with brine (1 x 50 mL), dried (Na SO ) and filtered.
2
4
After concentration in vacuo, the residue was purified by flash
chromatography (SiO , CHCl :MeOH:NH = 95:4:1). Yield: 11:
2
3
3
X-ray data were collected with a Bruker AXS Smart CCD area
detector diff r a c t o m, eg rt a ep hr ite monochromatized Mo Ka r a d -i a
t i o n (, M o -a K) = 0.71073 Å, and a Bruker AXS Kryoflex cooling
unit. Data reductions including corrections for absorption were car-
ried out with Bruker AXS programs [17]. The structures were
solved with direct methods using program SHELXS97 and were
1
colorless crystals 0.75 g (58%), mp 200-203 °C, H NMR
CDCl ): d 8.72 (d, J = 10.6 Hz, 1H), 6.63 (d, J = 8.0 Hz, 1H),
(
6
1
(
3
.40 (d, J = 8.0 Hz, 1H), 5.87 (d, J = 10.6 Hz, 1H), 4.31 (d, J =
6.7 Hz, 1H), 3.76 (s, 3H), 3.64 (d, J = 16.7 Hz, 1H), 3.55-3.39
m, 1H), 2.92-2.73 (m, 1H), 2.71-2.25 (m, 3H), 2.22-2.01 (m,