Penta-N-Protected Homocaldopentamine
J . Org. Chem., Vol. 63, No. 23, 1998 8203
31.43, 30.38 (CH3), 29.27, 28.34, 12.29, 0.00 (CH3) ppm; CIMS
m/z 450.5 [M + H]+.
(CHCl3) 2100 (N3), 1740 (CdO), 1360 (SO2), 1210 (CO), 1170
(SO2) cm-1; 1H NMR (CDCl3) δ 7.79 (d, J ) 8.29 Hz, 2H), 7.36
(d, J ) 8.07 Hz, 2H), 4.06 (t, J ) 5.27 Hz, 2H), 3.31-3.23 (m,
6H), 2.46 (s, 3H), 1.98-1.81 (m, 10H) ppm; 13C NMR (CDCl3)
δ 153.59, 144.99, 129.93, 127.95, 106.70, 88.80, 68.00 (CH2O),
49.04 (CH2N3), 45.50, 44.66, 28.22, 27.57, 21.65 (CH3), 21.60
ppm; CIMS m/z 532.0 [M + NH4]+.
3-Azid op r op yl 1-p-Tolu en esu lfon a te (8). Sodium azide
(11.66 g, 0.18 mol) was added to a solution of 3-chloropropan-
1-ol (7, 5 mL, 59.76 mmol) in DMF (40 mL). The reaction
mixture was heated at 60 °C for 24 h. Then it was diluted
four times with water and extracted with diethyl ether three
times. The organic layer was dried over Na2SO4 and concen-
trated in vacuo. The crude compound (6 g, 99%) was used in
to the next step without purification.
ter t-Bu tyl N-[9-Allyl-16-a zid o-13-(2,2,2-tr ich lor o-ter t-
b u t oxyca r b on yl)-5-(t r im et h ylsilylet h ylsu lfon yl)-5,9,13-
tr ia za h exa d ec-1-yl]ca r ba m a te (1). A stirred solution of 2
(358 mg, 0.80 mmol), 3 (493 mg, 0.96 mmol), diisopropylethyl-
amine (0.2 mL, 1.20 mmol), and sodium iodide (187 mg, 1.22
mmol) in toluene (60 mL) was heated at 100 °C for 72 h. It
was cooled to room temperature and filtered. The filtrate was
washed with water once, and the water layer was extracted
with dichloromethane twice. The organic layer was combined,
dried over Na2SO4, concentrated in vacuo, and purified by flash
column chromatography (30:1 dichloromethane/methanol) to
provide the polyamine 1 as a colorless oil (441 mg, 70%): IR
νmax (CHCl3) 3440 (NH), 2100 (N3), 1700 (CdO), 1370 (SO2),
1160 (SO2) cm-1; 1H NMR (CDCl3) δ 5.81-5.70 (m, 1H), 5.15-
5.06 (m, 2H), 4.55 (br.s, 1H), 3.31-3.23 (m, 4H), 3.21-3.13
(m, 6H), 3.10-3.08 (m, 2H), 3.06-3.01 (m, 2H), 2.83-2.77 (m,
2H), 2.37-2.30 (m, 4H), 1.87 (s, 6H), 1.85-1.80 (m, 2H), 1.75-
1.62 (m, 4H), 1.58-1.42 (m, 4H), 1.39 (s, 9H), 0.97-0.91 (m,
2H), 0.00 (s, 9H) ppm; 13C NMR (CDCl3) δ 157.96, 137.20 (CHd
CH2), 130.25, 130.00, 127.25, 119.37 (CH2dCH), 90.51, 58.90,
55.38, 53.12, 52.95, 51.08, 49.84, 49.75, 48.30, 47.10, 30.39
(CH3), 29.27, 28.97, 28.38, 23.62 (CH3), 12.31, 0.00 (CH3) ppm;
ESIMS m/z 792.4 [M + H]+.
Gen er a l P r oced u r e for th e Acyla tion of Tetr a -N-
P r otected P en ta m in es. A solution of p-methoxycinnamoyl
chloride (1.1 equiv of polyamines) in absolute ethyl acetate (5
mL) was added dropwise over 5 min to a solution of polyamine
(0.06-0.08 mmol) and Et3N (1.5 equiv of polyamines) in
absolute ethyl acetate (10 mL) at -10 °C. The reaction
mixture was allowed to stir at -10 °C for 30 min and at room
temperature for 16-18 h. It was filtered and then concen-
trated in vacuo. Flash chromatography of the residue (20:1-
30:1 dichloromethane/methanol) provided acylpolyamines as
a colorless oil.
2,2,2-Tr ich lor o-ter t-bu tyl N-{4-Allyl-N-(3-a zid op r op yl)-
12-[3-(p-m eth oxyp h en yl)p r op -2-en oyla m in o]-8-(tr im eth -
ylsilyleth ylsu lfon yl)-4,8-d ia za d od ec-1-yl}ca r ba m a te (12).
Rem ova l of BOC Gr ou p fr om 1 (11). A solution of 1 (50
mg, 0.06 mmol) in dichloromethane (3 mL) was added at once
to a solution of trifluoroacetic acid (0.23 mL, 3.04 mmol) in
dichloromethane (10 mL) under argon at room temperature.
The reaction mixture was stirred for 40 min and then the
solvent and the excess of trifluoroacetic acid were evaporated
under reduced pressure. The residue was dissolved in dichlo-
romethane, washed with saturated aqueous Na2CO3 once,
dried over Na2SO4, and concentrated in vacuo, to lead to the
primary amine 11 as a colorless oil (40 mg).
Acyla tion of 11 (12). According to the general procedure
of the acylation, the reaction of 11 (40 mg) with p-methoxy-
cinnamoyl chloride (13 mg, 0.07 mmol) and Et3N (0.01 mL,
0.10 mmol) afforded the acylpolyamine 12 (37 mg, 70%): IR
νmax (CHCl3) 3420 (NH), 2100 (N3), 1730 (CdO), 1510 (CdO),
1375 (SO2), 1175 (SO2) cm-1; 1H NMR (CDCl3): δ 7.57 (d, J )
15.59 Hz, 1H), 7.45 (d, J ) 8.72 Hz, 2H), 6.88 (d, J ) 8.76 Hz,
2H), 6.38-6.20 (m, 1H), 6.00-5.70 (m, 2H), 5.25-5.08 (m, 2H),
3.82 (s, 3H), 3.47-3.38 (m, 2H), 3.35-3.20 (m, 10H), 3.11-
3.03 (m, 2H), 2.89-2.83 (m, 2H), 2.49-2.40 (m, 4H), 1.92 (s,
6H), 1.90-1.59 (m, 10H), 1.11-0.98 (m, 2H), 0.00 (s, 9H) ppm;
13C NMR (CDCl3) δ 170.46 (CdO), 139.98 (CHdCH2), 129.32,
114.26, 107.55, 55.36 (CH3), 49.12, 46.56, 39.03, 26.12, 21.68
(CH3), 10.36, 0.00 (CH3) ppm; ESIMS m/z 852.5 [M + H]+.
ter t-Bu tyl N-{9-Allyl-16-a zid o-5-[3-(p-m eth oxyp h en yl)-
p r op -2-en oyl]-13-(2,2,2-t r ich lor o-ter t-b u t oxyca r b on yl)-
5,9,13-tr ia za h exa d ec-1-yl}ca r ba m a te (14). Rem ova l of
SES Gr ou p fr om 1 (13). CsF (46 mg, 0.30 mmol) was added
at once to the reaction flask filled with argon. A solution of 1
(60 mg, 0.08 mmol) in DMF (4 mL) was added dropwise at
room temperature, and then it was heated to 95 °C. After 24
To the solution of the crude compound (6 g) in dichlo-
romethane (60 mL) were added DMAP (1.45 g, 11.88 mmol)
and Et3N (12.42 mL, 89.12 mmol). And then a solution of
p-toluenesulfonyl chloride (17 g, 89.12 mmol) in dichlo-
romethane (30 mL) was added dropwise at 0 °C. The reaction
mixture was stirred at 0 °C for 30 min and warmed to room
temperature. After 12 h of stirring, it was diluted with
dichloromethane (100 mL) and washed with saturated aqueous
NaHCO3, 10% aqueous HCl, and 10% brine continuously. The
organic layer was dried over Na2SO4 and concentrated in
vacuo. The purification by flash column chromatography (3:1
hexane/ethyl acetate) gave 8 as a colorless oil (12 g, 80%): IR
ν
max (CHCl3) 2100 (N3), 1370 (SO2), 1190 (SO2) cm-1; 1H NMR
(CDCl3): δ 7.80 (d, J ) 8.33 Hz, 2H), 7.36 (d, J ) 8.22 Hz,
2H), 4.11 (t, J ) 5.99 Hz, 2H), 3.38 (t, J ) 6.49 Hz, 2H), 2.45
(s, 3H), 1.89 (quint, J ) 6.24 Hz, 2H) ppm; 13C NMR (CDCl3)
δ 145.05, 132.82, 132.28, 129.95, 129.89, 128.07, 127.92, 67.03
(CH2O), 60.39, 56.16, 47.31 (CH2N3), 28.48, 21.65, 14.21 ppm;
CIMS m/z 273.3 (32, [M + NH4]+), 204.2 (100).
N-(3-Azid op r op yl)-3-a m in op r op a n -1-ol (9). To a reflux-
ing solution of 3-aminopropan-1-ol (7.4 mL, 96.08 mmol) and
anhydrous K2CO3 (9.47 g, 68.63 mmol) in toluene (150 mL)
was added dropwise a solution of 8 (7 g, 27.45 mmol) in toluene
(40 mL) over 50 min. The solution was refluxed for 24 h using
a Dean-Stark apparatus. It was cooled to room temperature
and filtered. The filtrate was concentrated in vacuo and given
to flash column chromatography (10:1:0.1 dichloromethane/
methanol/25% ammonia water) to provide 9 as a colorless oil
(3.73 g, 86%): IR νmax (CHCl3) 3610 (OH), 3300 (NH), 2100
(N3), 1070 (CO) cm-1 1H NMR (CDCl3): δ 3.81 (t, J ) 5.36
;
Hz, 2H), 3.36 (t, J ) 6.67 Hz, 2H), 2.88 (t, J ) 5.77 Hz, 2H),
2.72 (t, J ) 6.87 Hz, 4H), 1.81-1.69 (m, 4H) ppm; 13C NMR
(CDCl3): δ 64.26 (CH2O), 49.96, 49.53, 47.01 (CH2N3), 30.83,
29.15 ppm; CIMS m/z 159.2 [M + H]+.
2,2,2-Tr ich lor o-ter t-bu tyl N-[3-Azid o-N-(3-h yd r oxyp r o-
p yl)-p r op -1-yl]ca r ba m a te (10). To a solution of 9 (1 g, 6.32
mmol) in a mixture of 1 M solution of NaOH (30 mL) and
diethyl ether (30 mL) was added dropwise over 1 h a solution
of 2,2,2-trichloro-tert-butoxycarbonyl chloride (2.43 g, 10.11
mmol) in diethyl ether (25 mL) at 0 °C. The reaction mixture
was stirred for 30 min at 0 °C and separated. The water phase
was extracted with diethyl ether twice. During the separation
and extraction, the reaction mixture should be kept cold. The
organic phases were combined, dried over Na2SO4, and con-
centrated in vacuo. The purification by flash column chroma-
tography (1:1 hexane/ethyl acetate) afforded 10 as a colorless
oil (1.71 g, 75%): IR νmax (CHCl3) 3610 (OH), 2100 (N3), 1740
1
(CdO), 1250 (CO), 1060 (CO) cm-1; H NMR (CDCl3) δ 3.59
(t, J ) 5.55 Hz, 2H), 3.44-3.28 (m, 6H), 2.70 (br s, 1H), 1.95-
1.86 (m, 8H), 1.78-1.70 (quint, J ) 5.85 Hz, 2H) ppm; 13C
NMR (CDCl3) δ 154.97, 106.67, 89.56, 60.40 (CH2O), 60.18,
58.53, 49.09 (CH2N3), 45.14, 43.66, 31.78, 30.60, 28.13, 27.59,
21.63, 21.04 (CH3), 14.21 ppm; CIMS m/z 360.9 [M + H]+.
2,2,2-Tr ich lor o-ter t-bu tyl N-{3-Azid o-N-[3-(p-tolylsu l-
fon yloxy)-p r op yl]-p r op -1-yl}ca r ba m a te (3). A solution of
p-toluenesulfonyl chloride (950 mg, 4.98 mmol) in dichlo-
romethane (70 mL) was added dropwise over 1 h to a solution
of 10 (1.2 g, 3.32 mmol), Et3N (0.7 mL, 4.98 mmol), and DMAP
(487 mg, 3.98 mmol) in dichloromethane (100 mL) at 0 °C. The
reaction mixture was stirred at 0 °C for 30 min and at room
temperature for 24 h. Then, it was diluted with dichlo-
romethane, washed with 10% aqueous HCl and 10% brine,
dried over Na2SO4 and concentrated in vacuo. The residue
was purified by flash chromatography (hexane/ethyl acetate
2.5:1) to provide 3 as a colorless oil (1.19 g, 70%): IR νmax