Motuporamines
J . Org. Chem., Vol. 67, No. 1, 2002 257
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H2O (22 mL) and Et2O (3 × 7 mL). The resulting â-amino ester
was then reacted with a 10-fold excess of 1,3-diaminopropane,
and the resulting amide was reduced with LAH as described
above to give the motuporamine analogue 49.
Com p ou n d 27: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.27 (m, 2H), 3.13 (m, 6H), 3.05 (t, J
) 9.6 Hz, 2H), 2.96 (tm, J ) 7.8 Hz, 2H), 2.15 (m, 2H), 2.09
(m, 2H), 1.68 (m, 4H), 1.36 (m, 4H), 1.30 (m, 16H) 0.89 (t, J )
6.5 Hz, 6H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 54.4, 50.8,
46,0, 45.9, 37.8, 32.8, 30.2, 30.1, 27.6, 25.3, 24.7, 23.6, 22.0,
14.4 ppm; positive-ion HRFABMS [M + H]+ m/z 356.3988
(C22H50N3, calcd 356.4005).
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Com p ou n d 16: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.67 (b, 2H), 3.30 (m, 2H), 3.07-3.17
(m, 6H), 3.05 (t, J ) 7.6 Hz, 2H), 2.01-2.21 (m, 8H) ppm; 13
C
NMR (100 MHz, MeOH-d4) δ 55.3, 52.9, 45.9, 45.9, 37.8, 25.3,
24.0, 23.9 ppm; positive-ion HRFABMS [M + H]+ m/z 186.1964
(C10H24N3, calcd 186.1970).
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Com p ou n d 28: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.25 (m, 2H), 3.13 (m, 6H), 3.05 (m,
2H), 2.96 (tm, J ) 7.8 Hz, 2H), 2.14 (m, 2H), 2.11 (m, 2H),
1.68 (m, 4H), 1.36 (m, 4H), 1.29 (m, 24H) 0.89 (t, J ) 6.7 Hz,
6H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 54.3, 50.9, 46,0,
45.9, 37.8, 33.0, 30.6, 30.5, 30.4, 30.2, 27.6, 25.4, 24.7, 23.7,
22.0, 14.4 ppm; positive-ion HRFABMS [M + H]+ m/z 412.4621
(C26H58N3, calcd 412.4631).
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Com p ou n d 17: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.53 (bd, J ) 8.5 Hz, 2H), 3.11-3.21
(m, 6H), 3.05 (t, J ) 6.1 Hz, 2H), 2.93 (bt, J ) 9.2 Hz, 2H),
2.17 (m, 2H), 2.09 (m, 2H), 1.95 (m, 2H), 1.79 (m, 2H), 1.52
(m, 2H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 54.8, 54.5, 46.0,
37.8, 25.4, 24.2, 24.2, 22.6, 22.1 ppm; positive-ion HRFABMS
[M + H]+ m/z 200.2128 (C11H26N3, calcd 200.2127).
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Com p ou n d 29: isolated as an amorphous solid; H NMR
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Com p ou n d 18: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 7.28 (m, 3H), 7.20 (m, 1H), 4.49 (b,
2H), 3.62 (b, 2H), 3.41 (m, 2H), 3.15-3.24 (m, 6H), 3.06 (t, J
) 7.6 Hz, 2H), 2.29 (m, 2H), 2.10 (m, 2H) ppm; 13C NMR (100
MHz, MeOH-d4) δ 132.0, 129.9, 129.6, 128.5, 128.4, 127.9, 54.3,
54.0, 51.4, 46.0, 45.9, 37.8, 26.2, 25.4, 22.4 ppm; positive-ion
HRFABMS [M + H]+ m/z 248.2131 (C15H26N3, calcd 248.2127).
(400 MHz, MeOH-d4) δ 3.37 (m, 4H), 3.25 (m, 2H), 3.10-3.17
(m, 4H), 3.05 (bt, J ) 7.8 Hz, 2H), 2.20 (m, 2H), 2.09 (m, 2H),
1.90 (m, 4H), 1.67 (m, 4H), 1.64 (m, 4H) ppm; 13C NMR (100
MHz, MeOH-d4) δ 54.3, 52.2, 46.0, 45.9, 37.8, 25.4, 25.1, 24.7,
22.8, 22.6 ppm; positive-ion HRFABMS [M + H]+ m/z 242.2587
(C14H32N3, calcd 242.2596).
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Com p ou n d 30: isolated as an amorphous solid; H NMR
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Com p ou n d 19: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.53 (bd, J ) 11.8 Hz, 1H), 3.35 (2H),
3.08-3.21 (m, 5H), 3.05 (t, J ) 7.6 Hz, 2H), 2.85 (tm, J ) 11.0
Hz, 1H), 2.27 (m, 1H), 2.15 (m, 2H), 2.09 (m, 2H), 1.91 (m,
2H), 1.69-1.89 (m, 4H), 1.57 (m, 1H), 1.45 (m, 1H), 1.26-1.40
(m, 3H), 1.17 (m, 1H) ppm; 13C NMR (100 MHz, MeOH-d4) δ
68.7, 54.3, 50.2, 46.0, 46.0, 41.6, 37.8, 33.6, 30.7, 28.6, 26.1,
25.9, 25.3, 24.2, 21.2 ppm; positive-ion HRFABMS [M + H]+
m/z 254.2585 (C15H32N3, calcd 254.2596).
(400 MHz, MeOH-d4) δ 3.29 (m, 4H), 3.25 (m, 2H), 3.13 (m,
4H), 3.06 (m, 2H), 2.18 (m, 2H), 2.09 (m, 2H), 1.87 (m, 4H),
1.53 (m, 6H), 1.50 (m, 6H) ppm; 13C NMR (100 MHz, MeOH-
d4) δ 53.8, 53.6, 50.0, 45.9, 37.8, 25.9, 25.8, 25.3, 24.8, 23.0,
22.5 ppm; positive-ion HRFABMS [M + H]+ m/z 270.2909
(C16H36N3, calcd 270.2909).
Com p ou n d 20: isolated as cubic crystals; mp 168-171 °C;
1H NMR (400 MHz, MeOH-d4) δ 3.25 (m, 2H), 3.15 (m, 8H),
3.05 (t, J ) 7.6 Hz, 2H), 2.18 (m, 2H), 2.09 (m, 2H), 1.69 (m,
4H), 1.45 (m, 10H), 1.37 (m, 12H) ppm; 13C NMR (100 MHz,
MeOH-d4) δ 52.8, 52.7, 50.0, 45.9, 37.8, 27.7, 27.6, 27.6, 27.5,
27.1, 25.3, 25.2, 22.7, 22.5 ppm; positive-ion HRFABMS [M +
H]+ m/z 340.3684 (C21H46N3, calcd 340.3692).
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Com p ou n d 31: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.77 (m, 2H), 3.72 (m, 1H), 3.32 (m,
2H), 3.08-3.17 (m, 4H), 3.05 (bt, J ) 7.6 Hz, 2H), 2.33 (m,
1H), 2.19 (m, 2H), 2.09 (m, 2H), 2.03 (m, 6H), 1.80 (m, 2H),
1.67 (m, 4H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 62.2, 62.1,
55.9, 46.0, 46.0, 39.9, 37.8, 36.8, 35.2, 33.3, 31.7, 29.1, 27.0,
26.6, 25.3, 23.1 ppm; positive-ion HRFABMS [M + H]+ m/z
266.2587 (C16H32N3, calcd 266.2596).
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Com p ou n d 21: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.25 (bm, 2H), 3.17 (bm, 8H), 3.07 (bm,
2H), 2.17 (bm, 2H), 2.10 (bm, 2H), 1.71 (bm, 4H), 1.41 (bm,
10H), 1.34 (m, 16H) ppm; 13C NMR (100 MHz, MeOH-d4) δ
53.0, 52.5, 46.1, 46.0, 37.8, 28.8, 28.6, 28.5, 28.2, 28.1, 27.8,
26.4, 25.4, 23.5, 22.5 ppm; positive-ion HRFABMS [M + H]+
m/z 368.3995 (C23H50N3, calcd 368.4005).
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Com p ou n d 33: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.81 (bs, 4H), 3.65 (bs, 12H), 3.47 (t, J
) 4.8 Hz, 4H), 3.38 (m, 2H), 3.17 (t, J ) 7.6 Hz, 2H), 3.15 (t,
J ) 7.6 Hz, 2H), 3.05 (t, J ) 7.8 Hz, 2H), 2.21 (m, 2H), 2.10
(m, 2H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 71.0, 70.5, 70.0,
55.5, 55.5, 52.8, 46.0, 45.9, 37.8, 25.4, 21.5 ppm; positive-ion
HRFABMS [M + H]+ m/z 334.2710 (C16H36N3O4, calcd
334.2706).
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Com p ou n d 22: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 5.36 (m, 2H), 3.25 (m, 2H), 3.14 (m,
8H), 3.05 (t, J ) 7.6 Hz, 2H), 2.16 (m, 2H), 2.04-2.12 (m, 6H),
1.70 (m, 4H), 1.40 (m, 10H), 1.35 (m, 8H) ppm; 13C NMR (100
MHz, MeOH-d4) δ 131.3, 130.7, 53.3, 53.0, 52.7, 46.0, 45.9,
37.8, 30.2, 30.1, 29.2, 29.2, 29.1, 28.6, 28.2, 27.8, 27.8, 26.9,
25.9, 25.4, 24.3, 23.2, 22.4 ppm; positive-ion HRFABMS [M +
H]+ m/z 366.3844 (C23H48N3, calcd 366.3848).
Com p ou n d 34: isolated as an oil; 1H NMR (400 MHz,
MeOH-d4) δ 2.64 (t, J ) 5.9 Hz, 4H), 1.55 (m, 4H), 1.39 (m,
16H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 48.0, 28.1, 27.3,
27.0, 26.5, 25.4 ppm; positive-ion HRFABMS [M + H]+ m/z
184.2069 (C12H26N, calcd 184.2065).
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Com p ou n d 23: isolated as an amorphous solid; H NMR
Com p ou n d 37: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 5.32 (m, 2H), 3.25 (m, 2H), 3.13 (m,
8H), 3.04 (t, J ) 7.4 Hz, 2H), 2.16 (m, 2H), 2.08 (m, 2H), 2.00
(m, 4H), 1.67 (m, 4H), 1.31-1.43 (m, 18H) ppm; 13C NMR (100
MHz, MeOH-d4) δ 132.2, 131.9, 52.8, 52.4, 51.9, 46.0, 45.9,
37.8, 32.9, 32.9, 29.8, 29.7, 29.3, 29.0, 28.6, 28.4, 27.9, 26.6,
25.7, 25.3, 24.0, 22.6, 22.2 ppm; positive-ion HRFABMS [M +
H]+ m/z 366.3854 (C23H48N3, calcd 366.3848).
(400 MHz, MeOH-d4) δ 3.23 (m, 2H), 3.19 (m, 4H), 3.03 (t, J
) 7.4 Hz, 2H), 2.11 (m, 2H), 1.77 (m, 4H), 1.49 (m, 4H), 1.41
(m, 12H) ppm; 13C NMR (100 MHz, MeOH-d4) δ 53.4, 53.2,
37.8, 26.7, 25.9, 25.6, 25.3, 23.7, 22.3 ppm; positive-ion
HRFABMS [M + H]+ m/z 241.2638 (C15H33N2, calcd 241.2644).
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Com p ou n d 38: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.23 (m, 4H), 3.16 (m, 2H), 3.09 (t, J
) 6.4 Hz, 2H), 3.02 (t, J ) 6.3 Hz, 2H), 2.13 (m, 2H), 1.77 (m,
4H), 1.67 (m, 2H), 1.42 (m, 18H), 0.99 (t, J ) 7.4 Hz, 3H) ppm;
13C NMR (100 MHz, MeOH-d4) δ 53.4, 53.1, 48.9, 45.7, 29.3,
26.7, 25.9, 25.6, 25.3, 22.5, 22.4, 20.8, 13.9 ppm; positive-ion
HRFABMS [M + H]+ m/z 297.3277 (C19H41N2, calcd 297.3270).
Com p ou n d 39. Partial conversion to the trifluoroacetate
adduct occurred on concentration in vacuo after HPLC puri-
fication; hence, this compound was isolated as the free base
since the final step, extraction and evaporation of the Et2O,
provided analytically pure product. isolated as an oil; 1H NMR
(400 MHz, MeOH-d4) δ 3.61 (t, J ) 6.3 Hz, 2H), 2.67 (t, J )
7.3 Hz, 2H), 2.62 (t, J ) 7.4 Hz, 2H), 2.39 (m, 4H), 1.72
(quintet, J ) 6.6 Hz, 2H), 1.66 (quintet, J ) 7.1 Hz, 2H), 1.45
(m, 4H), 1.38 (m, 18H), ppm; 13C NMR (100 MHz, MeOH-d4)
Com p ou n d s 24 a n d 25: isolated as an amorphous solid;
1H NMR (400 MHz, MeOH-d4) δ 5.38 (m, 4H), 2.57 (m, 6H),
2.44 (m, 6H), 2.36 (m, 12H), 2.07-1.97 (m, 16H), 1.49 (m, 16H),
1.30 (m, 28H) ppm; 13C NMR (100 MHz, MeOH-d4) consisted
of very broad and complex resonances with chemical shifts as
expected; positive-ion HRFABMS [M + H]+ m/z 730.7538
(C46H95N6, calcd 730.7546).
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Com p ou n d 26: isolated as an amorphous solid; H NMR
(400 MHz, MeOH-d4) δ 3.23 (m, 2H), 3.13 (m, 6H), 3.05 (t, J
) 7.8 Hz, 2H), 2.96 (tm, J ) 7.8 Hz, 2H), 2.16 (m, 2H), 2.09
(m, 2H), 1.69 (m, 4H), 1.36 (m, 12H), 0.92 (t, J ) 6.9 Hz, 6H)
ppm; 13C NMR (100 MHz, MeOH-d4) δ 54.4, 50.8, 46.0, 45.9,
37.8, 32.4, 27.3, 25.4, 24.7, 23.5, 22.0, 14.2 ppm; positive-ion
HRFABMS [M + H]+ m/z 300.3378 (C18H42N3, calcd 300.3379).