414 J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 3
Reddy et al.
(CDCl3) δ 1.00 (t, 3H), 1.40 (m, 10H), 2.29 (s, 6H), 2.57 (b, 14H),
3.13 (m, 8H), 6.93 (s, 4H); 13C NMR (CDCl3) δ 12.72, 20.90,
22.72, 22.78, 24.67, 24.80, 30.80, 40.02, 41.61, 44.56, 45.10,
45.38, 131.87, 140.04, 142.21, 142.28; MS-FAB (m/z) calcd
552.80 (M+ + 1), found 552.81.
1,6,11-Tr is(m e sit yle n e su lfon yl)-1,6,11-t r ia za t r id e -
ca n e (12) was prepared (97%) from 11 as described for 4: 1H
NMR (CDCl3) δ 0.96 (t, 3H), 1.38 (m, 8H), 2.29 (s, 9H), 2.55
(s, 6H), 2.56 (s, 6H), 2.59 (s, 6H), 2.80 (m, 2H), 3.10 (m, 8H),
4.67 (t, 1H), 6.93 (s, 6H); 13C NMR (CDCl3) δ 12.56, 20.87,
22.70, 22.74, 22.84, 24.40, 26.45, 24.67, 26.62, 39.87, 41.88,
44.45, 45.02, 45.09, 131.86, 131.90, 133.12, 133.12, 133.32,
133.68, 138.91, 139.97, 142.02, 142.02, 142.21, 142.38; MS-
FAB (m/z) calcd 734.04 (M+), found 734.05.
49.32, 49.69, 129.11, 129.39; MS-ESI (m/z) calcd 356.61 (M+
+ 1), found 356.60.
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
18,23-p en ta za -(15Z)-p en ta cosen e (18) was prepared (52%)
from 12 and 13 as described for 14: 1H NMR (CDCl3) δ 0.95
(m, 6H), 1.32 (m, 12H), 2.29 (s, 15H), 2.55 (s, 30H), 3.06 (m,
16H), 3.70 (m, 4H), 5.47 (m, 2H), 6.92 (s, 10H); 13C NMR
(CDCl3) δ 12.67, 20.90, 22.71, 22.76, 24.43, 24.68, 39.97, 42.08,
44.48, 44.90, 45.61, 128.28, 128.45, 131.87, 131.93, 132.01,
139.96, 140.00, 140.12, 142.21, 142.28, 142.58; MS-FAB (m/z)
calcd 1266.80 (M+), found 1266.81.
3,8,13,18-P en taaza-(15Z)-pen tacosen e pen tah ydr och lo-
r id e (19) was prepared (96%) from 18 as described above for
15: 1H NMR (D2O) δ 1.28 (t, 6H), 1.78 (m, 12H), 3.09 (m, 16H),
3.84 (m, 4H), 5.96 (m, 2H); 13C NMR (D2O) δ 13.31, 25.61,
25.73, 45.70, 46.79, 49.05, 49.36, 49.65, 129.19; MS-ESI (m/z)
calcd 356.61 (M+ + 1), found 356.60.
3N,8N-Bis(m esitylen esu lfon yl)-12-ch lor o-3,8-diaza-(10Z)-
d od ecen e (13) was prepared (99%) from 4 and 1,4-dichloro-
1
2-butene as described for 9: H NMR (CDCl3) δ 1.01 (t, 3H),
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
23-p en ta za -(5Z,20Z)-p en ta cosa d ien e (20). A mixture of
potassium hydroxide (0.25 g), potassium carbonate (0.25 g) and
tetrabutylammonium bromide (0.05 g) was suspended in 15
mL benzene, mesitylenesulfonamide (0.2 g, 1 mmol) was added
to the suspension and the mixture was heated at 50 °C. Iodide
14 (2.0 g, 3 mmol) in 10 mL benzene was added, the mixture
heated under reflux for 18 h, then cooled to 20 °C, the inorganic
solids filtered off, washed with benzene (2 × 20 mL), and the
combined benzene layers washed several times with water
until the washings were neutral. The benzene was dried
(MgSO4), evaporated to dryness and the residue purified by
column chromatography using hexanes-ethyl acetate (7.5:2.5)
as eluant; 0.95 g (25%) of 20 was obtained: 1H NMR (CDCl3)
δ 1.00 (t, 6H), 1.28 (m, 8H), 2.29 (s, 15H), 2.53 (s), 2.55 (s),
2.57 (s), 3.03 (m, 8H), 3.12 (q, 4H), 3.70 (m, 8H), 5.47 (m, 4H),
6.93 (s, 10H); 13C NMR (CDCl3) δ 12.78, 20.85, 22.63, 22.69,
24.32, 24.58, 40.41, 41.43, 42.00, 44.76, 45.43, 128.08, 128.83,
131.88,131.95, 132.77, 132.85, 133.23, 139.90. 140.00, 140.08,
142.22, 142.43,142.53; MS-FAB (m/z) calcd 1264.78 (M+), found
1264.79.
1.38 (m, 4H), 2.29 (s, 3H), 2.30 (s, 3H), 2.57 (s, 6H), 2.61 (s,
6H), 3.11 (m, 4H), 3.16 (q, 2H), 3.81 (d, 2H), 3.98 (d, 2H), 5.51
(m, 1H), 5.77 (m, 1H), 6.93 (s, 2H), 6.95 (s, 2H); 13C NMR
(CDCl3) δ 12.76, 20.91, 22.71, 22.76, 24.74, 38.12, 40.08, 41.85,
44.59, 129.14, 129.25, 131.88, 132.02, 140.19, 142.21, 142.63;
MS-FAB (m/z) calcd 569.22 (M+ ), found 569.23.
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
18,23-p en ta a za -(15Z,20Z)-p en ta cosa d ien e (14) was pre-
pared (78%) from 12 and 9 following the procedure described
above for 9. It was purified by column chromatography using
hexane-ethyl acetate (7:3) as eluant: 1H NMR (CDCl3) δ 0.97
(t, 3H), 0.99 (t, 3H), 1.29 (m, 8H), 2.29 (s, 15H), 2.54, 2.55,
2.59 (s, 3H), 3.06 (m, 12H), 3.65 (m, 8H), 5.48 (m, 4H), 6.92 (s,
10H); 13C NMR (CDCl3) δ 12.70, 12.83 20.88, 20.91, 22.65,
22.68, 22.72, 22.74, 24.48, 24.72, 40.04, 40.47, 41.53, 42.07,
42.22, 42. 34, 44.54, 44.96, 127.94, 128.27, 129.20, 131.92,
132.05, 139.96, 140.00, 140.12, 140.16, 140.27, 142.19, 142.25,
142.47, 142.58, 142.87; MS-FAB (m/z) calcd 1264.78 (M+),
found 1264.77.
3,8,13,18-Tetr a a za -(15Z,20Z)-p en ta cosa d ien e P en ta h y-
d r och lor id e (15). Pentamide 14 (0.93 g, 0.735 mmol) was
dissolved in 20 mL anhydrous methylene chloride; phenol (3.5
g,36.8 mmol) was added, followed by 30% HBr in glacial acetic
acid (17.6 mL). The mixture was stirred overnight at 25 °C.
Water (10 mL) was added, the aqueous layer was separated,
the organic layer extracted with 5 mL of water, and the
combined aqueous layers were washed with methylene chlo-
ride (6 × 15 mL). The aqueous layer was evaporated under
vacuum to a solid residue that was dissolved in 1 mL 1 N
sodium hydroxide followed by 1 mL 50% potassium hydroxide.
The solution was extracted with chloroform (10 × 5 mL), the
combined organic layers were dried (MgSO4), evaporated, and
the residue dissolved in dry ethyl ether. Dry hydrogen chloride
was passed through the solution kept at 0 °C; pentahydro-
chloride 15 (0.33 g, 84%) precipitated, it was filtered and
washed with ether: 1H NMR (D2O) δ 1.29 (t, 3H), 1.31 (t, 3H),
1.79 (m, 8H), 3.12 (m, 12H), 3.87 (m, 8H), 5.98 (m, 4H); 13C
NMR (D2O) δ 13.36, 13.46, 25.66, 25.77, 45.44, 45.74, 46.24,
46.41, 46.84, 49.09, 49.41, 49.70, 129.02, 12916, 129.47, 129.66;
MS-ESI (m/z) calcd 354.59 (M+ + 1), found 354.60. Anal.
(C20H48Cl5N5) C, H, N.
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
18,23-p en ta a za -(20Z)-p en ta cosen e (16) was prepared (51%)
from 12 and 8 as described above for 14: 1H NMR (CDCl3) δ
0.97 (t, 3H), 0.99 (t, 3H), 1.29 (m, 12H), 2.29 (s, 15H), 2.55 (s),
2.56 (s), 2.57 (s), 3.10 (m, 16H), 3.70 (m, 4H), 5.47 (m, 2H),
6.93 (s, 10H); 13C NMR (CDCl3) δ 12.69, 12.83, 20.91, 22.69,
22.71, 22.76, 24.43, 24.70, 40.48, 41.11, 41.48, 44.50, 44.91,
128.13, 128.90, 131.88, 131.94, 132.01, 133.29, 139.95, 140.00,
140.15, 142.22, 142.29, 142.60; MS-FAB (m/z) calcd 1266.80
(M+), found 1266.79.
3,8,13,18,23-Tet r a a za -(5Z,20Z)-p en t a cosa d ien e p en -
ta h yd r och lor id e (21) was prepared (57%) from 20: 1H NMR
(D2O) δ 1.31 (t, 6H), 1.78 (m, 8.H), 3.15 (m, 12H), 3.83 (m,
8H), 5.96 (m, 4H); 13C NMR (CDCl3) δ 13.43, 25.64, 25.76,
45.39, 46.19, 46.77, 49.35, 49.72, 129.11, 129.41; MS-ESI (m/
z) calcd 354.59 (M+ + 1), found 354.60. Anal. (C20H48Cl5N5) C,
H, N.
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
18,23-p en ta a za -(5Z,10Z,15Z,20Z)-p en ta cosa tetr a en e (22)
was prepared (24%) from 9 and mesitylenesulfonamide as
1
described for 20: mp 58 °C; H NMR (CDCl3) δ 0.99 (t, 6H),
2.29 (s, 15H), 2.53 (s), 2.55 (s), 3.12 (q, 4H), 3.63 (m, 16H),
5.49 (m, 8H), 6.93 (s, 10H); 13C NMR (CDCl3) δ 12.85, 20.89,
20.92, 22.66, 40.47, 41.53, 42.19, 128.00, 128.47, 128.58,
129.11, 131.92, 132.05, 140.17, 140.30, 142.46, 142.87; MS-
FAB (m/z) calcd 1260.75 (M+), found 1260.76.
3,8,13,18,23-P en t a za -(5Z,10Z,15Z,20Z)-p en t a cosa t et -
r a en e p en ta h yd r och lor id e (23) was prepared (81%) from
22 as described above for 15: 1H NMR (D2O) δ 1.31 (t, 6H),
3.15 (q, 4H), 3.84 (m, 4H), 3.90 (m, 12H), 5.98 (m, 8H); 13C
NMR (D2O) δ 13.42, 45.41, 46.22, 46.44, 129.07, 129.37, 129.42,
129.58; MS-MALDI (m/z) calcd 350.56 (M+ + 1), found 350.55.
Anal. (C20H44Cl5N4) C, H, N.
3N,8N,13N,18N,23N-P en ta k is(m esitylen esu lfon yl)-3,8,13,-
18,23-p en ta a za -(10Z,15Z)-p en ta cosa d ien e (24) was pre-
pared (25%) from 13 as described above for 20: mp 62 °C; 1H
NMR (CDCl3) δ 0.95 (quint, 6H), 1.33 (m,8H), 2.29 (s, 15H),
2.54 (s), 2.55 (s), 3.07 (m, 12H), 3.65 (m, 8H), 5.48 (m,4H), 6.92
(s, 10H); 13C NMR (CDCl3) δ 12.69, 20.90,22.69, 22.73, 24.70,
40.03, 42.13, 42.30, 44.53, 45.59, 128.11, 128.79, 131.87,
132.00, 140.02, 140.14, 140.28, 142.17, 142.58, 142.85; MS-
FAB (m/z) calcd 1264.78 (M+), found 1264.79.
3,8,13,18,23-P en ta za -(20Z)-p en ta cosen e p en ta h yd r o-
ch lor id e (17) was prepared (79%) from 16 as described above
for 15: 1H NMR (D2O) δ 1.29 (t, 3H), 1.30 (t, 3H), 1.78 (m,
12H), 3.12 (m, 16H), 3.83 (m, 4H), 5.96 (m, 2H); 13C NMR (D2O)
δ 13.31, 13.42, 25.62, 25.75, 45.38, 45.71, 46.18, 46.76, 49.07,
3,8,13,18,23-P en ta a za -(10Z,15Z)-p en ta cosa d ien e p en -
ta h yd r och lor id e (25) was prepared from 24 (87%) as de-
1
scribed above for 15: H NMR (D2O) δ 1.28 (t, 6H), 1.79 (m,
8H), 3.10 (m, 12H), 3.87 (m, 8H), 5.98 (m, 4H); 13C NMR (D2O)