9730 J . Org. Chem., Vol. 64, No. 26, 1999
Notes
MHz, CD3OD) δ 7.15-7.31 (10H, m), 5.02 (2H, s), 4.40 (1H, m),
3.90 (1H, m), 3.78 (1H, m), 3.25 (1H, m), 2.79-2.88 (2H, m),
2.40-2.46 (2H, m), 2.07 (1H, m), 1.75 (1H, s); 13C NMR (75 MHz,
CD3OD) δ 171.8, 157.9, 140.3, 137.9, 130.0 (2C), 129.7 (2C), 129.6
(2C), 129.3, 129.1 (2C), 127.6, 81.0, 67.9, 51.1, 49.1, 35.3, 31.9,
22.4. Anal. Calcd for C21H24N2O4: C, 68.46; H, 6.57; N, 7.60.
Found: C, 68.50; H, 6.57; N, 7.64.
(1S,11bR)-1-Amino-1,2,3,6,7,11b-hexahydro-9,10-dimethoxy-
ben zo[a ]qu in olizin -4-on e (12b). A solution of 9b (0.18 g, 0.4
mmol) in MeOH (10 mL) was stirred at room temperature under
H2 (1 atm) with a catalytic amount of 10% palladium on charcoal
(0.02 g) for 2h. The reaction mixture was filtered through Celite-
545, concentrated, and purified by flash column chromatography
(MeOH/CH2Cl2 ) 1:20) to give 12b (0.09 g, 78%) as a white
foam: [R]25D -34.2° (c 1.2, MeOH); IR (CHCl3) 3422, 2938, 1616,
1518, 1466 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.18 (1H, s), 6.66
(1H, s), 4.63 (1H, m), 4.30 (1H, d, J ) 7.3 Hz), 3.87 and 3.88
(6H, two s), 3.23 (1H, m), 2.86-2.93 (2H, m), 2.40-2.67 (3H,
m), 2.00 (1H, m), 1.77 (1H, m) 1.59 (2H, br s, NH2); 13C NMR
(75 MHz, CDCl3) δ 170.2, 148.5, 147.7, 129.1, 127.8, 112.1, 110.1,
63.2, 56.6, 56.3, 51.8, 41.4, 30.0, 29.4, 29.0; HRMS (EI) calcd for
C15H20N2O3 m/z 276.1474, found 276.1472.
(1S ,12b S )-1-(Be n zyloxyca r b on yl)a m in o-1,2,3,6,7,12b -
h exa h yd r o-in d olo[2,3-a ]qu in olizin -4-on e (9a ). To a solution
of hydroxylactam 7a (0.1 g, 0.25 mmol) in acetonitrile (4 mL)
was added dropwise BF3‚Et2O (0.1 mL, 0.7 mmol) at -78 °C,
and the mixture was slowly warmed to -10 °C. After stirring
for 5 h, the reaction mixture was diluted with CH2Cl2 (30 mL)
and quenched by addition of aqueous NaHCO3. The organic layer
was separated, washed with brine, dried (MgSO4), and concen-
trated. The residue was purified by flash column chromatogra-
phy (EtOAc/n-hexane/CH2Cl2 ) 6:3:1) to afford hydroxylactam
(1S,12b S)-1-Am in o-1,2,3,4,6,7,12,12b -oct a h yd r o-in d olo-
[2,3-a ]qu in olizin e (2). A solution of AlCl3 (25.8 mg, 0.19 mmol)
in THF (1 mL) was added dropwise to a solution of LiAlH4 (44
mg, 1.16 mmol) in THF (1 mL) at -78 °C under argon
atmosphere, and the mixture was slowly warmed to room
temperature. After stirring for 30 min, this suspension was
added to a solution of 12a (49.7 mg, 0.19 mmol) in THF (2 mL)
at -78 °C under an argon atmosphere. The reaction mixture
was allowed to warm to room temperature and stirred for 2 h.
The reaction mixture was cooled to 0 °C and quenched by careful
addition of ether (5 mL), Na2SO4‚10H2O (0.24 g), and Celite-
545. The mixture was stirred at room temperature for 1 h and
filtered through Celite-545. The filtrate was concentrated and
purified by flash column chromatography (MeOH/CH2Cl2 ) 1:20)
to give 2 (35 mg, 74%) as a white solid: mp 132.5-135.0 °C (dec);
9a (63 mg, 66%) as a foam: [R]24 -28.8° (c 0.17, MeOH); IR
D
1
(CHCl3) 3270, 1694, 1634 cm-1; H NMR (300 MHz, CD3OD) δ
9.30 (1H, br s), 7.48 (1H, d, J ) 7.6 Hz), 7.37 (5H, s), 7.32 (1H,
d, J ) 7.9 Hz), 7.19 (1H, t, J ) 6.7 Hz), 7.12 (1H, t, J ) 7.7 Hz),
5.90 (1H, d, J ) 8.0 Hz), 5.21 (2H, s), 5.02 (1H, dd, J ) 11.5, 4.4
Hz), 4.68 (1H, d, J ) 5.2 Hz), 4.19 (1H, br s), 2.76-2.92 (2H,
m), 2.67 (1H, d, J ) 13.7 Hz), 2.30-2.58 (2H, m), 1.85-2.09 (2H,
m); 13C NMR (75 MHz, CD3OD) δ 169.1, 156.7, 136.2, 136.0,
131.8, 128.8 (2C), 128.6 (2C), 128.2, 126.6, 122.3, 119.7, 118.3,
111.5, 110.1, 67.5, 59.9, 50.5, 41.9, 29.8, 25.9, 20.7. Anal. Calcd
for C23H23N3O3: C, 70.93; H, 5.95; N, 10.79. Found: C, 70.82;
H, 6.04; N, 10.68. Chiral HPLC analysis: chiral column, Chira-
Spher NT 250 mm × 4 mm i.d.; eluting solvents, MeOH/i-PrOH/
n-hexane ) 83:7.4:5.6; flow rate, 1.3 mL/min; detector, UV (280
nm), retention time, 11.6 min.
[R]23 +3.64° (c 0.17, MeOH); IR (KBr) 3348, 3266, 2924, 2800,
D
2746, 1460, 1316 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.57 (1H,
s), 7.47 (1H, d, J ) 7.6 Hz), 7.32 (1H, d, J ) 7.8 Hz), 7.11 (1H,
t, J ) 7.1 Hz), 7.04 (1H, t, J ) 7.1 Hz), 2.91-3.13 (4H, m), 2.82
(1H, td, J ) 10.5, 4.1 Hz), 2.55-2.76 (2H, m), 2.34 (1H, td, J )
(1S ,11b R )-1-(Be n zyloxyca r b on yl)a m in o-1,2,3,6,7,11b -
h exa h yd r o-9,10-d im eth oxyben zo[a ]qu in olizin -4-on e (9b).
Cyclized product 9b was prepared from hydroxylactam 7b (0.53
g, 1.3 mmol) following a procedure similar to that of 9a in 94%
yield (0.47 g) as a foam: [R]24D -42.6° (c 0.7, MeOH); IR (CHCl3)
3270, 1716, 1632 cm-1; 1H NMR (300 MHz, CD3OD) δ 7.26 (5H,
m), 6.89 (1H, s), 6.69 (1H, s), 4.80 and 5.04 (2H, ABq, J ) 12.4
Hz), 4.48 (1H, d, J ) 7.4 Hz), 4.29 (1H, m), 4.04 (1H, m), 3.74
(3H, s), 3.55 (3H, s), 2.78-2.95 (2H,m), 2.53-2.70 (2H, m), 2.38
(1H, m), 1.86-2.01 (2H, m); 13C NMR (75 MHz, CD3OD) δ 169.4,
156.9, 148.3, 147.6, 136.3, 128.6 (2C), 128.2 (2C), 127.0, 120.8,
111.8, 108.1, 67.0, 60.9, 55.9, 49.5, 42.1, 28.9, 28.0, 24.7, 17.4.
Anal. Calcd for C23H26N2O5: C 67.30; H 6.38; N 6.82. Found: C
67.18; H 6.41; N 6.75. Chiral HPLC analysis: chiral column,
ChiraSpher NT 250 mm × 4 mm i.d.; eluting solvents, MeOH/
i-PrOH/n-hexane ) 83:7.4:5.6; flow rate, 1.3 mL/min; detector,
UV (280 nm), retention time, 13.9 min.
(1S,12bS)-1-Am in o-1,2,3,6,7,12b-h exa h yd r o-in d olo[2,3-a ]-
qu in olizin -4-on e (12a ). A solution of 7a (0.24 g, 0.6 mmol) in
MeOH (10 mL) was stirred at room temperature under H2 (1
atm) with a catalytic amount of 10% palladium on charcoal (0.02
g) for 3 h. The reaction mixture was filtered through Celite-545
and concentrated to give 12a (0.16 g) in quantitative yield as a
white foam: [R]25D -75.0° (c 1.1, MeOH); IR (CHCl3) 3356, 2918,
1620, 1464, 1442 cm-1; 1H NMR (300 MHz, CDCl3) δ 10.05 (1H,
s), 7.49 (1H, d, J ) 7.7 Hz), 7.34 (1H, d, J ) 7.9 Hz), 7.16 (1H,
t, J ) 7.5 Hz), 7.09 (1H, t, J ) 7.4 Hz), 5.10 (1H, m), 4.29 (1H,
d, J ) 10.0 Hz), 2.71-2.98 (4H, m), 2.61 (1H, m), 2.45 (1H, m),
1.90 (1H, m), 1.76 (1H, m), 1.64 (2H, br s, NH2); 13C NMR (75
MHz, CDCl3) δ 168.5, 135.9, 134.2, 126.8, 122.2, 119.7, 118.6,
111.5, 108.9, 59.6, 53.1, 41.1, 33.1, 31.8, 21.4; HRMS (EI) calcd
for C15H17N3O m/z 255.1372, found 255.1371.
11.5, 3.2 Hz), 2.08 (1H, m), 1.66-1.90 (4H, m), 1.25 (1H, m); 13
C
NMR(75 MHz, CDCl3) δ 135.9, 135.8, 127.3, 121.3, 119.0, 118.3,
111.4, 107.8, 65.9, 55.7, 54.2, 53.3, 39.2, 25.1, 22.1; HRMS (EI)
1
calcd for C15H19N3 m/z 241.1579, found 241.1577. The H NMR
spectroscopic data of 2 was in accord with that described in the
literature for racemic mixture.3a
(1S,11bR)-1-Amino-1,2,3,6,7,11b-hexahydro-9,10-dimethoxy-
ben zo[a ]qu in olizin e (3). Compound 3 was prepared from
hydroxylactam 12b (52 mg, 0.2 mmol) following a procedure
similar to that of 2 in 75% yield (37 mg) as a viscous oil: [R]25
D
+17.1° (c 1.4, MeOH); IR (CHCl3) 3420, 2934, 1516, 1460, 1264,
1134 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.89 (1H, s), 6.54 (1H,
s), 3.78 (6H, s), 4.30 (1H, d, J ) 7.9 Hz), 3.18 (1H, m), 3.09 (1H,
m), 2.67-2.93 (5H, m), 2.02 (2H, br s), 1.64-1.88 (2H, m), 1.55
(1H, m),1.42 (1H, m); 13C NMR (75 MHz, CDCl3) δ 148.0, 146.3,
128.3, 127.2, 112.4, 111.2, 65.9, 56.4, 56.1, 53.5, 48.8, 47.4, 33.9,
28.4, 21.4; HRMS (EI) calcd for C15H22N2O2 m/z 262.1681, found
262.1682.
Ack n ow led gm en t. Financial support from the Min-
istry of Science and Technology, Korea (2E14578) is
gratefully acknowledged. Elemental analyses data were
provided by Specific Analysis Center at Korea Institute
of Science and Technology. High (EI) resolution mass
spectra were obtained at Korea Basic Science Institute.
J O9911950