476
L. F. Tietze – N. Rackelmann · Enantioselective Synthesis of Epi-Emetine Analogues
column chromatography (silica gel, eluent: CH2Cl2/MeOH 55.78, 55.90 (4× OMe), 107.2, 107.5, 109.4, 111.6 (C-5’,
10:1) to give the diastereomers 9 (> 96% ee) and 10 (80% C-8, C-8’, C-11), 126.3, 126.9, 128.7 132.4 (C-4’a, C-7a,
ee) as yellow oils (27 mg, 60%).
C-8’a, C-11a), 147.1 147.3, 150.6, 151.3 (C-6’, C-7’,
C-8, C-11). – MS (70 eV, EI): m/z (%) = 480.4(40)
[M+], 449.4(58) [M+–OMe], 288.1(40) [M+–C11H14NO2],
272.3(100) [M+–C12H17NO2], 192.2(60) [C11H14NO+2 ];
C29H40N2O4 (480.64): calcd. 480.2988; found 480.2988.
1(S)-2,3(S,R)-11b(R)-2-(6,7-Dimethoxy-1,2,3,4-tetra-
hydro-isoquinolin-1-yl-methyl)-3-ethyl-8,11-dimethoxy-
1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline (9)
[α]2D0 = +28.3◦ (c = 0.60 in CHCl3). – UV/vis (CH3CN):
λmax (lg ε) = 200.0 nm (4.836), 287.0(3.824). – IR (KBr):
ν = 3332, 2932 (C-H), 2832 (OMe), 1463 cm−1 (CH2). –
1H NMR (600 MHz, CDCl3): δ = 0.91 (t, 3J = 7.5 Hz,
3 H, 13-H), 1.38 (mz, 1 H), 1.54 (mz, 1 H), 1.69 – 1.83 (m,
2-(8,11-Dimethoxy-4-oxo-1,3,4,6,7,11b-hexahydro-2H-
pyrido[2,1-a]-isoquinolin-2-yl)-butyraldehyde (27)
A suspension of 17 (800 mg, 1.33 µmol) and a catalytic
amount of Pd/C in MeOH (10.0 cm3) was stirred under a
H2-atmosphere for 4.0 h. The catalyst was filtered off and
the solvent was removed under reduced pressure. The crude
product was purified by column chromatography (silica gel,
eluent: toluene/acetone, 10:1). The title compound was ob-
tained as a mixture of diastereomers (50 mg, 12%).
2
3 H), 1.86 – 1.98 (m, 2 H), 2.12 (ddd, J = 13.9 Hz, 3J =
2
8.9,3.3 Hz, 1 H), 2.28 (mz, 1 H), 2.49 (ddd, J = 10.7 Hz,
3J = 9.8,3.7 Hz, 1 H), 2.64 (mz, 1 H), 2.69 – 2.80 (m,
4 H), 2.87 (ddd, 2J = 10.9 Hz, 3J = 4.8,4.8 Hz, 1 H),
2.97 (dd, 2J = 12.6 Hz, 3J = 3.9 Hz, 1 H), 3.00 (mz,
1 H), 3.24 (mz, 1 H), 3.66 (mz, 1 H), 3.69, 3.74 (s, 2 ×
OMe), 3.84 (s 6 H, 2 × OMe), 3.93 (mz, 1 H), 6.57 (s,
1 H) 6.60 (s, 3 H). – 13C NMR (150 MHz, CDCl3):
δ = 12.88 (C-13), 25.17 (C-12), 26.88 (C-4’ or C-7),
29.55 (C-4’ or C-7), 31.13 (C-1), 34.98 (C-2), 39.99 (C-3),
40.29 (C-α or C-3’), 40.69 (C-α or C-3’), 49.83 (C-6),
52.67 (C-1’), 54.13 (C-11b), 55.28 (C-4), 55.33, 55.64,
55.83, 56.06 (4× OMe), 107.2, 107.7, 109.7, 111,7 (C-5’,
C-8, C-8’, C-11), 126.6, 127.2, 129.3, 132.4 (C-4’a, C-7a,
C-8’a, C-11a), 147.1, 147.3, 150.9, 151.2 (C-6’, C-7’,
C-8, C-11). – MS (70 eV, EI): m/z (%) = 480.4(40)
[M+], 449.4(70) [M+–OMe], 286.1(40) [M+–C11H12NO2],
272.3(100) [M+–C12H17NO2], 192.2(60) [C11H14NO+2 ];
C29H40N2O4 (480.64): calcd. 480.2988; found 480.2988.
UV/vis (CH3CN): λmax (lg ε) = 197.5 nm (4.713),
288.5(3.639).
– IR (KBr): ν = 3423, 2936 (C-H),
2837 (OMe), 1720 (CHO), 1632 (R2NCOR), 858 cm−1
1H NMR (300 MHz, CDCl3): δ = 0.82 – 0.97 (m,
.
–
3 H), 1.49 – 1.80 (m, 3 H), 2.01 – 2.73 (m, 6 H), 2.74 –
3.07 (m, 2 H), 3.72 – 3.81 (m, 6 H), 4.69 – 4.99 (m, 2 H),
6.65 – 6.70 (m, 2 H), 9.60 – 9.67 (m, 1 H). – 13C NMR
(50 MHz, CDCl3): δ = 11.29, 11.37, 11.41 (C-4’), 18.89,
19.12, 19.66 (C-3’), 22.62, 22.72, 23.54 (C-7), 28.99,
29.40, 31.03 (C-2), 32.72, 33.58, 33.80 (C-3), 35.16,
35.60 (C-1), 37.94, 38.19 (C-6), 49.74, 49.91, 54.35 (C-11b),
55.37, 55.73 (OMe), 57.15, 57.37, 57.96 (C-2’), 108.1,
108.2, 108.2, 108.3, 108.4 (C-9 and C-10), 125.7, 125.7,
125.8, 125.9, 126.0, 126.3 (C-7a, C-11a), 168.6, 170.4,
170.5 (C-4), 203.9, 204.1 (C-1’). – MS (70 eV, EI):
m/z (%) = 331.2(24) [M+], 258.1(100) [C15H16NO+3 ],
191.1[C11H13NO+2 ]; C19H25NO4 (331.41); calcd. 331.1784;
found 331.1784.
1(S)-2,3(R,S)-11b(S)-2-(6,7-Dimethoxy-1,2,3,4-tetrahydro-
isoquinolin-1-yl-methyl)-3-ethyl-8,11-dimethoxy-1,3,4,6,
7,11b-hexahydro-2H-pyrido[2,1-α]isoquinoline (10)
[α]2D0 = −14.8◦ (c = 0.40 in CHCl3). – UV/vis (CH3CN):
λmax (lg ε) = 200.0 nm (4.824), 287.0(3.786). – IR (KBr):
ν = 3332, 2934 (C-H), 2832 (OMe), 1463 cm−1 (CH2).
1H NMR (600 MHz, CDCl3): δ = 0.91 (t, 3J = 7.5 Hz,
2-(8,11-Dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyr-
ido[2,1-a]-isoquinolin-2-yl)-butanol (28)
To a stirred suspension of lithium aluminium hydri◦de
3 H, 13-H), 1.17 (mz, 1 H), 1.54 (mz, 1 H), 1.63 (ddd, 2J = (29 mg, 0.75 mmol) in tetrahydrofuran (1 cm3) at −50 C
14.3 Hz, 3J = 11.5,3.1 Hz, 1 H), 1.70 (mz, 1 H), 1.77 (ddd, a solution of the aldehyde 27 (25 mg, 75.4 µmol) in tetra-
2J = 14.1 Hz, 3J = 11.0,4.1 Hz, 1 H), 1.94 (mz, 1 H), hydrofuran (2 cm3) was added dropwise. The reaction mix-
2.34 (ddd, 2J = 14.2 Hz, 3J = 12.2,2.2 Hz, 1 H), 2.43 (mz, ture was stirred for 4.5 h at 25 ◦C and quenched with water
1 H), 2.58 (ddd, 2J = 14.1 Hz, 3J = 11.0,4.1 Hz, 1 H), (0.03 cm3). After stirring for 10 min an aqueous sodium hy-
2
2.63 – 2.84 (m, 5 H), 2.90 – 3.02 (m 3 H), 3.20 (ddd, J = droxide solution (0.03 cm3, 15%) was added, stirring was
3
14.2 Hz, J = 12.2,2.2 Hz, 1 H), 3.71, 3.75, 3.81, 3.84 (s, continued for 10 min and water (0.07 cm3) was added again.
4 × OMe), 3.92 (mz, 1 H), 4.20 (mz, 1 H), 6.57 (s, 1 H), The formed precipitate was removed by filtration and washed
6.62 (s, 2 H), 6.76 (s, 1 H). – 13C NMR (150 MHz, CDCl3): with tetrahydrofuran (20 cm3). The combined filtrates were
δ = 12.70 (C-13), 24.67 (C-12), 26.85 (C-4’ or C-7), evaporated under reduced pressure and the crude product
27.02 (C-4’ or C-7), 29.37 (C-1), 34.01 (C-2), 40.05 (C-α was purified by column chromatography (silica gel; eluent:
or C-3’), 40.17 (C-α or C-3’), 42.40 (C-3), 49.37 (C-6), CH2Cl2/MeOH; 10:1). The title compound was obtained as
52.48 (C-1’), 54.72 (C-11b), 54.89 (C-4), 55.20, 55.58, a yellow oil (8 mg, 44%).
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