3132 J . Org. Chem., Vol. 63, No. 9, 1998
Notes
J ) 8.6 Hz, 2H), 7.31-7.59 (m, 11H), 7.85-8.00 (m, 4H); 13C
NMR (CDCl3) δ 168.8, 159.3, 150.8, 147.2, 136.0, 132.3 (m), 131.3
(m), 129.8, 128.7 (m), 128.2, 127.4, 127.2, 116.0, 114.1, 113.8,
110.7, 71.1, 56.2, 55.2, 47.7, 42.0 (d, J ) 76.5 Hz); 31P NMR
120.7, 119.9, 114.0, 110.0, 107.7, 98.9, 60.3, 56.9, 55.8, 55.2, 43.3;
IR (KBr) 1730, 1695 cm-1
H, 5.40; N, 3.26. Found: C, 72.93; H, 5.54; Br, 3.07.
. Anal. Calcd for C26H23NO5: C, 72.71;
2-(Be n zyloxy)-1,7-d im e t h oxy-5-[(4-m e t h oxyp h e n yl)-
m eth yl]-d iben z[cd ,f]in d ol-4(5H)-on e (6): mp 170-171 °C; 1H
NMR (CDCl3) δ 3.74 (s, 3H), 3.98 (s, 3H), 4.11 (s, 3H), 5.10 (s,
2H), 5.29 (s, 2H), 6.82 (d, J ) 7.2 Hz, 2H), 7.03 (d, J ) 7.9 Hz,
1H), 7.29-7.68 (m, 9H), 7.87 (s, 1H), 8.84 (d, J ) 7.9 Hz, 1H);
13C NMR (CDCl3) δ 166.7, 158.9, 155.8, 153.3, 152.0, 136.5,
135.6, 129.3, 128.8, 128.7, 128.2, 127.5, 127.55, 126.2, 125.2,
121.1, 120.8, 120.1, 119.9, 114.1, 112.1, 107.7, 99.0, 72.1, 60.5,
(CDCl3) δ 30.8; IR (KBr) 1258, 1649 cm-1
.
Anal. Calcd for
36H33BrNO5P: C, 64.48; H, 4.96; N, 2.09. Found: C, 64.61; H,
5.19; N, 1.9.7.
C
Typ ica l P r oced u r e for th e Syn th esis of Ar ylm eth ylen e
Isoin d olin on es 10-12. A solution of KHMDS (14 mL, 0.5 M
in toluene, 7 mmol) was added dropwise over a period of 5 min
to a stirred solution of compounds 20, 21 (3.4 mmol) in THF (50
mL) at -78 °C under Ar. The solution was stirred for 30 min
at this temperature and then allowed to warm to -30 °C within
3 h. A solution of the appropriate aldehyde 15, 16 (3.4 mmol)
in THF (5 mL) was then added by syringe, and the reaction
mixture was allowed to warm to room temperature over a period
of 30 min. Aqueous NH4Cl was added, and the mixture was
extracted with Et2O (100 mL). The organic layer was washed
with water and brine, dried (MgSO4), and concentrated in vacuo
to a light yellow oil which was purified by flash column
chromatography with AcOEt-hexanes (75:25) as eluent.
3-[(2-Br om o-6-m eth oxyp h en yl)m eth ylen e]-2,3-d ih yd r o-
5,6-d im eth oxy-2-[(4-m eth oxyp h en yl)m eth yl]-1H-isoin d ol-
1-on e (10): E and Z isomers (ratio 80:20 from 1H NMR
spectrum). E isomer 1H NMR (CDCl3) δ 3.50 (s, 3H), 3.67 (s,
3H), 3.88 (s, 3H), 3.93 (s, 3H), 4.94 (d, J ) 15.9 Hz, 1H), 5.19 (d,
J ) 15.9 Hz, 1H), 5.99 (s, 1H), 6.29 (s, 1H), 6.84 (d, J ) 8.6 Hz,
2H), 6.88 (d, J ) 8.9 Hz, 1H), 7.16 (d, J ) 8.9 Hz, 1H), 7.19-
7.26 (m, 4H); Z isomer 1H NMR (partial) δ 3.51 (s, 3H), 3.69 (s,
3H), 6.32 (s, 1H); E isomer 13C NMR (CDCl3) δ 166.9, 158.7,
158.6, 152.2, 150.5, 137.1, 129.8, 129.3, 128.4, 126.1, 125.2, 124.9,
123.0, 113.9, 109.6, 105.1, 104.6, 104.5, 56.2, 56.0, 55.6, 55.3,
42.6. Anal. Calcd for C26H24BrNO5: C, 61.19; H, 4.74; N, 2.74.
Found: C, 61.01; H, 4.55; Br, 2.91.
55.8, 55.2, 43.3; IR (KBr) 1710, 1652 cm-1
. Anal. Calcd for
C32H27NO5: C, 76.02; H, 5.38; N, 2.77. Found: C, 75.92; H, 5.60;
N, 3.04.
7-(Be n zyloxy)-1,2-d im e t h oxy-5-[(4-m e t h oxyp h e n yl)-
m eth yl]-d iben z[cd ,f]in d ol-4(5H)-on e (7): mp 160-161 °C; 1H
NMR (CDCl3) δ 3.72 (s, 3H), 4.04 (s, 3H), 4.07 (s, 3H), 5.06 (s,
2H), 5.27 (s, 2H), 6.81 (d, J ) 7.4 Hz, 2H), 7.06 (d, J ) 7.6 Hz,
1H), 7.32 (d, J ) 7.4 Hz, 2H), 7.41-7.63 (m, 7H), 7.81 (s, 1H),
8.82 (d, J ) 7.6 Hz, 1H); 13C NMR (CDCl3) δ 167.7, 159.0, 154.8,
154.3, 151.4, 137.2, 135.6, 129.3, 129.1, 128.6, 128.0, 127.7, 127.3,
125.7, 125.6, 123.0, 121.0, 120.6, 120.3, 114.0, 110.0, 109.3, 99.3,
72.5, 60.3, 26.9, 55.2, 43.4; IR (KBr) 1707, 1647 cm-1
. Anal.
Calcd for C32H27NO5: C, 76.02; H, 5.38; N, 2.77. Found: C,
76.21; H, 5.15; N, 2.72.
Typ ica l P r oced u r e for th e O-Ben zyl Dep r otection of th e
Ar istola cta m s 6, 7. A mixture of aristolactam 6, 7 (0.1 mmol),
palladium on charcoal (10%, 10 mg), and ammonium formate
(63 mg, 1 mmol) in MeOH-CH2Cl2 (9:1, 75 mL) was refluxed
for 30 min. The reaction mixture was passed through a Celite
pad, and the filtrate was concentrated in vacuo. The residue
was dissolved in CH2Cl2 (50 mL), washed with water (2 × 10
mL) and brine, and dried (MgSO4). Concentration in vacuo
afforded a yellow solid which was recrystallized from EtOH.
6-(Ben zyloxy)-3-[(2-br om o-6-m eth oxyph en yl)m eth ylen e]-
2,3-d ih yd r o-5-m eth oxy-2-[(4-m eth oxyp h en yl)m eth yl]-1H-
2-Hyd r oxy-1,7-d im eth oxy-5-[(4-m eth oxyp h en yl)m eth yl]-
d iben z[cd ,f]in d ol-4(5H)-on e (8): mp 245-246 °C; 1H NMR
(DMSO-d6) δ 3.67 (s, 3H), 3.94 (s, 3H), 3.99 (s, 3H), 5.06 (s, 2H),
6.86 (d, J ) 8.0 Hz, 2H), 7.17 (d, J ) 8.1 Hz, 1H), 7.24 (d, J )
8.0 Hz, 2H), 7.43 (s, 1H), 7.49 (t, J ) 8.1 Hz, 1H), 7.69 (s, 1H),
8.73 (d, J ) 8.1 Hz, 1H), 10.41 (s, 1H); 13C NMR (DMSO-d6) δ
166.7, 158.4, 155.3, 152.3, 149.2, 135.4, 129.3, 128.3, 127.0, 125.9,
124.9, 120.9, 120.6, 120.3, 119.2, 114.0, 108.0, 97.4, 59.5, 55.8,
1
isoin d ol-1-on e (11): E and Z isomers (ratio 70:30 from H NMR
spectrum). E isomer 1H NMR (CDCl3) δ 3.51 (s, 3H), 3.69 (s,
3H), 3.78 (s, 3H), 4.91 (d, J ) 12.8 Hz, 1H), 5.11-5.25 (m, 3H),
5.99 (s, 1H), 6.29 (s, 1H), 6.84 (d, J ) 8.5 Hz, 2H), 6.87 (d, J )
8.1 Hz, 1H), 7.18-7.53 (m, 10H); Z isomer 1H NMR (partial) δ
3.52 (s, 3H), 3.72 (s, 3H), 3.78 (s, 3H), 6.01 (s, 1H), 6.35 (s, 1H);
E isomer 13C NMR (CDCl3) δ 166.9, 158.6, 152.8, 149.6, 137.1,
136.2,129.8, 129.3, 128.6, 128.4, 128.1, 127.3, 126.0, 124.7, 122.9,
113.9, 109.6, 106.6, 105.4, 104.5, 70.9, 56.0, 55.7, 55.3, 42.6. Anal.
Calcd for C32H28BrNO5: C, 65.54; H, 4.81; N, 2.39. Found: C,
65.38; H, 5.00; N, 2.44.
55.0, 42.2; IR (KBr) 3343, 1680, 1240 cm-1
. Anal. Calcd for
C25H21NO5: C, 72.28; H, 5.10; N, 3.37. Found: C, 72.21; H, 5.19;
N, 3.15.
7-Hyd r oxy-1,2-d im eth oxy-5-[(4-m eth oxyp h en yl)m eth yl]-
d iben z[cd ,f]in d ol-4(5H)-on e (9): mp 236-237 °C; 1H NMR
(DMSO-d6) δ 3.68 (s, 3H), 3.99 (s, 3H), 4.05 (s, 3H), 5.10 (s, 2H),
6.88 (d, J ) 7.6 Hz, 2H), 7.06 (d, J ) 6.8 Hz, 1H), 7.26 (d, J )
7.6 Hz, 2H), 7.36 (t, J ) 6.8 Hz, 1H), 7.45 (s, 1H), 7.93 (s, 1H),
8.60 (d, J ) 6.8 Hz, 2H), 10.15 (s, 1H); 13C NMR (DMSO-d6) δ
166.5, 158.4, 155.0,153.8, 152.8, 134.7, 129.7, 128.3, 127.8, 126.2,
123.7, 120.9, 120.2, 119.5, 118.0, 114.5, 112.5, 111.0, 99.0, 60.0,
55.1, 54.9, 42.5; IR (KBr) 3418, 1680, 1280 cm-1. Anal. Calcd
for C25H21NO5: C, 72.28; H, 5.10; N, 3.37. Found: C, 72.15; H,
5.02; N, 3.21.
3-[(2-(Ben zyloxy)-6-br om op h en yl)m eth ylen e]-2,3-d ih y-
d r o-5,6-d im eth oxy-2-[(4-m eth oxyp h en yl)m eth yl]-1H-isoin -
d ol-1-on e (12): E isomer, mp 153-154 °C; 1H NMR (CDCl3)
δ 3.41 (s, 3H), 3.71 (s, 3H), 3.93 (s, 3H), 4.88 (d, J ) 12.1 Hz,
1H), 4.95 (d, J ) 12.1 Hz, 1H), 5.00 (s, 2H), 6.02 (s, 1H), 6.23 (s,
1H), 6.72 (d, J ) 7.5 Hz, 2H), 6.92 (d, J ) 8.2 Hz, 1H), 6.97 (d,
J ) 7.5 Hz, 2H), 7.05-7.28 (m, 8H); 13C NMR (CDCl3) δ 167.0,
158.6, 152.2, 150.5, 137.2, 136.1, 129.7, 129.1, 128.4, 128.2, 127.9,
127.0, 126.2, 125.8, 125.2, 122.9, 113.9, 111.4, 105.0, 104.6, 104.2,
70.6, 56.2, 55.5, 42.6, 35.2; IR (KBr) 1695, 1639 cm-1
. Anal.
Calcd for C32H28BrNO5: C, 65.54; H, 4.81; N, 2.39. Found: C,
65.51; H, 4.65; N, 2.18.
Typ ica l P r oced u r e for th e Syn th esis of Ta lisca n in e (1),
Velu tin a m (2), a n d En ter oca r p a m II (3). A solution of
trifluoroacetic acid (114 mg, 1 mmol), anisole (110 mg, 1 mmol),
and aristolactam 5, 8, 9 (0.1 mmol) in dichloroethane (2 mL)
was refluxed under Ar for 24 h. The solvents were removed
under vacuum. The residue was dissolved in CH2Cl2 (20 mL),
and Et3N (0.5 mL) was added with stirring. Water (2 mL) was
then added, and the organic layer was washed with brine, dried
(MgSO4), and concentrated to yield a solid residue which was
recrystallized from EtOH. The analytical and spectral data of
synthetic 1-3 matched those reported for the natural products.
Typ ica l P r oced u r e for th e Syn th esis of Ar istola cta m s
5-7. To a solution of 10-12 (0.3 mmol) in dry degassed benzene
(150 mL), refluxing under Ar, was added a solution of n-Bu3-
SnH (130 mg, 0.45 mmol) and AIBN (25 mg, 0.15 mmol) in dry
degassed benzene (25 mL) dropwise over 10 min. Once addition
had finished, refluxing was kept up for a further 3 h. The
benzene was evaporated under reduced pressure, and the
residue was dissolved in CH3CN (100 mL). This solution was
washed with hexane (3 × 50 mL) and concentrated in vacuo to
a solid residue which was recrystallized from EtOH to obtain a
bright yellow solid.
1,2,7-Tr im eth oxy-5-[(4-m eth oxyp h en yl)m eth yl]-d iben z-
[cd ,f]in d ol-4(5H)-on e (5): mp 223-224 °C; 1H NMR (CDCl3) δ
3.73 (s, 3H), 3.98 (s, 3H), 4.05 (s, 3H), 4.07 (s, 3H), 5.10 (s, 2H),
6.82 (d, J ) 8.4 Hz, 2H), 7.02 (d, J ) 8.1 Hz, 1H), 7.33 (d, J )
8.4 Hz, 2H), 7.46 (t, J ) 8.1 Hz, 1H), 7.50 (s, 1H), 7.82 (s, 1H),
8.82 (d, J ) 8.1 Hz, 1H); 13C NMR (CDCl3) δ 167.8, 158.9, 155.7,
154.3, 151.5, 135.6, 129.3, 128.8, 127.9, 125.8, 125.2, 123.0, 121.1,
Ack n ow led gm en t. We thank Dr. T. G. C. Bird
(Zeneca Pharma) for helpful discussions. This research
was supported by the Centre National de la Recherche
Scientifique and MENESR (grant to C.H.).
J O972247T