428 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 3
Campos Rosa et al.
H-3), 6.57 (s, 2 H, CHdCH), 5.76 (s, 4 H, N+-CH2), 3.56-3.44
(m, 4 H, NH-CH2), 1.65 (m, 4 H, CH2), 1.38-1.29 (m, 12 H,
CH2); MS (FAB, MNOBA matrix) [M]+ 632, fragments at m/z
633, 631, 427, 206, 178, 157, 77, 43; HPLC (A:B ) 35:65) major
peak at 10.3 min representing 99.6% of the absorption. Anal.
(C44H48N42+‚2CF3COO-‚2.2CF3COOH‚2.2H2O) C, H, N.
Hz, 2 H, H-8), 8.00 (pt, J 1 ) J 2 ) 7.6 Hz, 2 H, H-7), 7.79 (d, J
) 7.9 Hz, 2 H, fluorene), 7.78 (pt, J 1 ) 7.9 Hz, J 2 ) 8.4 Hz, 2
H, H-6), 7.57 (dd, J 1 ) 1 Hz, J 2 ) 8 Hz, 2 H, fluorene), 7.53 (d,
J ) 8.4 Hz, 4 H, C6H4-C6H4), 7.45 (d, J ) 8.4 Hz, 4 H, C6H4-
C6H4), 7.02 (d, J ) 7.6 Hz, 2 H, H-3), 6.53 (s, 2 H, fluorene),
5.89 (s, 4 H, N+-CH2), 4.90 (d, J ) 5.7 Hz, 4 H, NH-CH2), 3.26
(s, 2 H, fluorene); MS (FAB, MNOBA matrix) [M]+ 658,
fragments at m/ z 657, 467, 192; HPLC (A:B ) 1:1) major peak
at 7.13 min representing 99.2% of the absorption. Anal.
(C47H38N42+‚2CF3COO-‚2CF3COOH‚6.6H2O) C, H, N.
9,20-Dia za -1,8(1,4)-d iq u in olin a -3,6(1,4)-d ib en zen a cy-
cloicosa p h a n ed iu m Tr itr iflu or oa ceta te Hyd r a te (2e).
Off-white powder: mp 202-204 °C; IR (Nujol mull) vmax 3179,
1
1685, 825, 765, 722; H NMR (400 MHz, DMSO-d6) δ 9.50 (t,
J ) 5.4 Hz, 2 H, NH), 8.71 (d, J ) 7.6 Hz, 2 H, H-2), 8.55 (d,
J ) 8.5 Hz, 2 H, H-8), 7.86-7.85 (m, 4 H, H-5 and H-6 or H-7),
7.69 (dt, J 1 ) 1.9 Hz, J 2 ) 7.6 Hz, 2 H, H-7 or H-6), 7.02-6.95
(m, 10 H, bibenzyl moiety), 5.70 (s, 4 H, N+-CH2), 3.60-3.40
(m, 4 H, NH-CH2), 2.93 (s, 4 H, C6H4-CH2-CH2-C6H4), 1.67-
1.58 (m, 4 H, CH2), 1.39-1.22 (m, 12 H, CH2); HPLC (A:B )
35:65) major peak at 8.15 min representing 100% of the
absorption. Anal. (C44H50N42+‚2CF3COO-‚1.2CF3COOH‚1.2H2O)
C, H, N.
9,15-Dia za -1,8(1,4)-d iqu in olin a -3,6,11,13(1,4)-tetr a ben -
zen a -4(Z)-en ecyclop en t a d eca p h a n ed iu m Dit r iflu or o-
a ceta te Tr ih yd r a te (3d ). Recrystallized from absolute EtOH/
Et2O to give a white powder: mp 267-269 °C dec; IR (KBr
disk) vmax 3214, 1685, 1339, 800, 767 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ 10.10 (t, J ) 6 Hz, 2 H, NH), 8.66 (d, J ) 8.5 Hz,
2 H, H-5), 8.58 (d, J ) 7.4 Hz, 2 H, H-2), 8.10 (d, J ) 9 Hz, 2
H, H-8), 7.98 (pt, J 1 ) 7.8 Hz, J 2 ) 7.9 Hz, 2 H, H-7), 7.76 (pt,
J 1 ) 7.5 Hz, J 2 ) 7.9 Hz, 2 H, H-6), 7.31 (d, J ) 8.4 Hz, 4 H,
C6H4-CH2-C6H4), 7.24 (d, J ) 8.4 Hz, 4 H, C6H4-CHdCH-C6H4),
7.21 (d, J ) 8.4 Hz, 4 H, C6H4-CH2-C6H4), 7.18 (d, J ) 8.4 Hz,
4 H, C6H4-CHdCH-C6H4), 6.88 (d, J ) 7.6 Hz, 2 H, H-3), 6.58
(s, 2 H, CHdCH), 5.74 (s, 4 H, N+-CH2), 4.79 (d, J ) 6 Hz, 4
H, NH-CH2), 3.88 (s, 2 H, C6H4-CH2-C6H4); MS (FAB, MNOBA
matrix) [M]+ 686, fragments at m/ z 685, 349, 206; HPLC (A:B
) 35:65) major peak at 8.14 min representing 100% of the
absorption. Anal. (C48H42N42+‚2CF3COO-‚3.4H2O) C, H, N.
7,18-Dia za -1,6(1,4)-d iq u in olin a -3,4(1,4)-d ib en zen a cy-
cloocta d eca n ep h a n ed iu m Tr itr iflu or oa ceta te Hyd r a te
(2f). Off-white powder: mp 280-282 °C; IR (Nujol mull) vmax
1
3170, 1684, 800, 758, 722 cm-1; H NMR (400 MHz, DMSO-
d6) δ 9.59 (t, 2 H, NH), 8.62 (d, J ) 7.3 Hz, 2 H, H-2), 8.61 (d,
J ) 9.7 Hz, 2 H, H-8), 8.51 (d, J ) 8.4 Hz, 2 H, H-5), 8.05 (t,
J ) 8.7 Hz, 2 H, H-6 or H-7), 7.73 (t, J ) 7.7 Hz, 2 H, H-7 or
H-6), 7.56 (m, 8 H, biphenyl moiety), 6.91 (d, J ) 7.9 Hz, 2 H,
H-3), 5.83 (s, 4 H, N+-CH2), 3.50-3.42 (m, 4 H, NH-CH2), 1.45
(m, 4 H, CH2), 1.22-1.06 (m, 12 H, CH2); MS (FAB, MNOBA
matrix) [M]+ 606, fragments at m/z 605, 180; HPLC (A:B )
4:6) major peak at 5.30 min representing 98.4% of the
absorption. Anal. (C42H46N42+‚2CF3COO-‚1.4CF3COOH‚1.4H2O)
C, H, N.
8,14-Dia za -1,7(1,4)-d iqu in olin a -3,5,10,12(1,4)-tetr a ben -
zen a cyclotetr a d eca p h a n ed iu m Tr itr iflu or oa ceta te Di-
h yd r a te (3a ). Off-white microcrystalline compound: mp 218-
220 °C dec; IR (KBr disk) vmax 3236, 1685, 832 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ 9.95 (t, J ) 5.8 Hz, 2 H, NH), 8.63 (d,
J ) 7.3 Hz, 2 H, H-5), 8.53 (d, J ) 7.6 Hz, 2 H, H-2), 8.11 (d,
J ) 9 Hz, 2 H, H-8), 7.94 (t, J ) 7.5 Hz, 2 H, H-7), 7.71 (t, J
) 7.8 Hz, 2 H, H-6), 7.28 (d, J ) 8.1 Hz, 4 H, C6H4-CH2-C6H4),
7.15 (d, J ) 8.1 Hz, 4 H, C6H4-CH2-C6H4), 7.14 (s, 8 H, C6H4-
CH2-C6H4), 6.96 (d, J ) 7.7 Hz, 2 H, H-3), 5.71 (s, 4 H, N+-
CH2), 4.79 (d, J ) 5.8 Hz, 4 H, NH-CH2), 3.91 (s, 2 H, C6H4-
CH2-C6H4), 3.85 (s, 2 H, C6H4-CH2-C6H4); MS (FAB, MNOBA
matrix) [M]+ 674, fragments at m/ z 673, 493, 480, 337, 193;
HPLC (A:B ) 4:6) major peak at 8.21 min representing 100%
of the absorption. Anal. (C48H42N42+‚2CF3COO-‚CF3COOH‚
2.2H2O) C, H, N.
8,13-Dia za -1,7(1,4)-d iqu in olin a -3,5,10,11(1,4)-tetr a ben -
zen a cyclotr id eca p h a n ed iu m Tetr a tr iflu or oa ceta te Hep -
ta h yd r a te (3b). Off-white powder: mp > 350 °C; IR (KBr
disk) vmax 3225, 1679, 1339, 805, 762 cm-1; 1H NMR (400 MHz,
DMSO-d6) δ 10.33 (t, J ) 6 Hz, 2 H, NH), 8.69 (d, J ) 8.4 Hz,
2 H, H-5), 8.64 (d, J ) 7.5 Hz, 2 H, H-2), 8.24 (d, J ) 9 Hz, 2
H, H-8), 8.02 (pt, J 1)7.9 Hz, J 2)8.1 Hz, 2 H, H-7), 7.82 (pt,
J 1)7.6 Hz, J 2)7.9 Hz, 2 H, H-6), 7.64 (d, J ) 8.3 Hz, 4 H,
C6H4-C6H4), 7.51 (d, J ) 8.3 Hz, 4 H, C6H4-C6H4), 7.00 (d, J )
8.6 Hz, 8 H, C6H4-CH2-C6H4), 6.65 (d, J ) 7.5 Hz, 2 H, H-3),
5.76 (s, 4H, N+-CH2), 4.86 (d, J ) 5.6 Hz, 4H, NH-CH2), 3.87
(s, 2 H, C6H4-CH2-C6H4); MS (FAB, MNOBA matrix) [M]+ 660,
fragments at m/z 659, 583; HPLC (A:B ) 45:55) major peak
at 8.54 min representing 100% of the absorption. Anal.
(C48H42N42+‚2CF3COO-‚2.5CF3COOH‚7H2O) C, H, N.
7,13-Dia za -1,6(1,4)-d iqu in olin a -3,4,9,11(1,4)-t et r a b en -
zen a cyclotr id eca p h a n ed iu m Tetr a tr iflu or oa ceta te Di-
h yd r a te (3e). White microcrystalline compound: mp 224-
226 °C dec; IR (KBr disk) vmax 3257, 1685, 1345, 800, 762 cm-1
;
1H NMR (400 MHz, DMSO-d6) δ 9.95 (t, J ) 5.6 Hz, 2 H, NH),
8.62 (d, J ) 9.6 Hz, 2 H, H-5), 8.60 (d, J ) 8.7 Hz, 2 H, H-2),
8.51 (d, J ) 8.4 Hz, 2 H, H-8), 8.06 (pt, J 1 ) 7.6 Hz, J 2 ) 7.7
Hz, 2 H, H-7), 7.75 (pt, J 1 ) 7.6 Hz, J 2 ) 7.9 Hz, 2 H, H-6),
7.57 (d, J ) 8.5 Hz, 4 H, C6H4-C6H4), 7.52 (d, J ) 8.5 Hz, 4 H,
C6H4-C6H4), 7.18 (d, J ) 8 Hz, 4 H, C6H4-CH2-C6H4), 7.07 (d,
J ) 8 Hz, 4 H, C6H4-CH2-C6H4), 7.00 (d, J ) 7.8 Hz, 2 H, H-3),
5.82 (s, 4 H, N+-CH2), 4.77 (d, J ) 5.6 Hz, 4 H, NH-CH2), 3.93
(s, 2 H, C6H4-CH2-C6H4); MS (FAB, MNOBA matrix) [M]+ 660,
fragments at m/ z 659, 480, 180; HPLC (A:B ) 45:55) major
peak at 8.86 min representing 100% of the absorption. Anal.
(C48H42N42+‚2CF3COO-‚2CF3COOH‚2H2O) C, H, N.
7,12-Dia za -1,6(1,4)-d iqu in olin a -3,4,9,10(1,4)-t et r a b en -
zen a cyclod od eca p h a n ed iu m Hexa tr iflu or oa ceta te Tet-
r a h yd r a te (3f). Off-white powder: mp 190-192 °C; IR (Nujol
1
mull) vmax 3183, 1652 cm-1; H NMR (400 MHz, DMSO-d6) δ
10.12 (t, 2 H, NH), 8.75 (d, 2 H, H-5 or H-8), 8.61 (d, 2 H,
H-2), 8.60 (d, 2 H, H-5 or H-8), 8.13 (t, 2 H, H-6 or H-7), 7.84
(t, 2 H, H-6 or H-7), 7.48 (d, 4 H, biphenyl), 7.42 (d, 8 H,
biphenyl), 7.37 (d, 4 H, biphenyl), 6.89 (d, 2 H, H-3), 5.81 (s, 4
H, N+-CH2), 4.79 (d, 4 H, NH-CH2); MS (FAB, MNOBA matrix)
[M - H]+ 645; HPLC (A:B ) 50:50) major peak at 7.08 min
2+
representing 96% of the absorption. Anal. (C46H38N4
‚
2CF3COO-‚4CF3COOH‚4H2O) C, H, N.
2,7-Dia za -1,8(4,1)-d iqu in olin a -4,5(1,4)-d iben zen a cyclo-
octa d eca p h a n ed iu m Tr iflu or oa ceta te Hyd r a te (3g). Yel-
low powder: mp 233-234 °C; IR (Nujol mull) vmax 3199, 1615
cm-1; 1H NMR (400 MHz, DMSO-d6) δ 10.35 (t, 2 H, NH), 8.67
(d, 2 H, H-5 or H-8), 8.49 (d, 2 H, H-2), 8.15 (d, 2 H, H-5 or
H-8), 8.01 (t, 2 H, H-6 or H-7), 7.80 (t, 2 H, H-6 or H-7), 7.66
(d, 4 H, biphenyl), 7.50 (d, 4 H, biphenyl), 6.57 (d, 2 H, H-3),
4.84 (d, 4 H, NH-CH2), 4.48 (t, 4 H, N+-CH2), 1.59 (m, 4 H,
CH2), 1.10-0.91 (m, 12 H, CH2); MS (FAB, MNOBA matrix)
[M - H]+ 605; HPLC (linear gradient from A:B ) 45:55 to A:B
) 20:80) major peak at 9.88 min representing 99.9% of the
absorption. Anal. (C42H46N42+‚2CF3COO-‚1.1CF3COOH‚1.1H2O)
C, H, N.
8,14-Dia za -1,7(1,4)-d iqu in olin a -4(2,6)-p yr id in a -3,5,10,
12(1,4)-t et r a b en zen a cyclot et r a d eca p h a n ed iu m Tr it r i-
flu or oa ceta te Dim eth a n ola te Tr ih yd r a te (3h ). Before
performing preparative HPLC, the product was treated with
boiling EtOH and the insoluble material was collected. This
was purified by preparative HPLC as detailed above. The
6,11-Dia za -1,5(1,4)-d iqu in olin a -3(2,7)-flu or en a -8,9(1,4)-
d ib en zen a cyclou n d eca p h a n ed iu m Tet r a t r iflu or oa ce-
tate Hexah ydr ate (3c). Before performing preparative HPLC,
the product was treated with a boiling mixture of EtOH/MeOH
and the insoluble material was collected. This was purified
by preparative HPLC as detailed above. The compound was
isolated as an off-white powder: mp 316-319 °C; IR (KBr disk)
vmax 3214, 1609, 1339, 803, 756 cm-1 1H NMR (400 MHz,
;
DMSO-d6) δ 10.28 (t, J ) 5.7 Hz, 2 H, NH), 8.73 (d, J ) 7.5
Hz, 2 H, H-2), 8.64 (d, J ) 9 Hz, 2 H, H-5), 8.40 (d, J ) 8.7