S. Orenes Lorente et al. / Bioorg. Med. Chem. 13 (2005) 5435–5453
5445
(CH2), 34.1 (CH), 37.0 (10-C), 37.3 (CH2), 38.5 (CH2),
39.5 (CH2), 39.9 (CH2), 42.7 (13-C), 45.4 (20-CH),
50.3 (9-CH), 51.8 (29-CH2), 53.2 (17-CH), 56.6 (14-
CH), 74.3 (3-CH), 122.9 (6-CH), 140.0 (5-C), 170.9
(10-C@O), 176.9 (22-C@O); MS (ES+) m/z (rel intensi-
ty) 487 (M+, 100); HRMS calcd for C30H51N2O3
([M + H]+): 487.3900; found: 487.3900. Anal. Calcd
for C30H50N2O3Æ0.72 H2O: C, 72.1; H, 10.4; N, 5.6;
Found: C, 72.1; H, 10.2; N, 5.3.
5.2.5.
3b-Acetoxy-23,24-bisnor-chol-5-en-22-oxo-22-
(trans-1,4)-diaminocyclohexyl (4e). 0.450 g, 72% yield;
mp 230–231 ꢁC; Rf = 0.26 (CHCl3:MeOH/NH4OH,
85:10:5); IR (KBr) 3319 (CONH str), 2939 (CH), 1729
(CH3CO), 1643 (CONH), 1533 (NHd), 1452 (CH2),
1373 (CH3), 1248 (C–O str), 1037, 607 cmꢀ1; H NMR
1
(300 MHz, CDCl3): d 0.68 (3H, s, 18-CH3), 1.02 (3H,
s, 19-CH3), 1.16 (3H, d, J = 7, 21-CH3), 1.21–1.99
(27H: 11· CH2, 5· CH), 2.04 (3H, s, 20-CH3), 2.32
(2H, d, J = 7, 4-CH2), 2.62 (1H, m, 29-CH), 3.68 (1H,
m, 24-CH), 4.60 (1H, m, 3-CH), 5.37 (1H, d, J = 4, 6-
CH), 5.66 (1H, d, J = 8, 23-NH); 13C NMR (75 MHz,
CDCl3): d 12.4 (18-CH3), 17.8 (21-CH3), 19.6 (19-
CH3), 21.3 (11- CH2), 21.8 (20-CH3), 24.7 (CH2), 27.7
(CH2), 28.1 (CH2), 31.9 (CH2), 32.1 (CH2), 32.1
(CH2), 32.2 (CH), 35.2 (CH2), 36.9 (10-C), 37.3 (CH2),
38.4 (CH2), 39.8 (CH2), 42.7 (13-C), 45.1 (CH), 47.8
(CH), 47.9 (29-CH), 50.0 (24-CH), 50.2 (9-CH), 53.2
(17-CH), 56.5 (14-CH), 74.5 (3-CH), 122.9 (6-CH),
140.0 (5-C), 171.3 (10-C@O), 176.8 (22-C@O); MS
(ES+) m/z (rel intensity) 485 (M+, 100); HRMS calcd
for C30H49N2O3 ([M + H]+): 485.3743; found:
485.3738. Anal. Calcd for C30H48N2O3Æ0.88 H2O: C,
72.0; H, 10.0; N, 5.6; Found: C, 71.9; H, 9.8; N, 5.3.
5.2.3.
3b-Acetoxy-23,24-bisnor-chol-5-en-22-oxo-22-
(1,8)-diaminooctyl (4c). 0.250 g, 40% yield; mp 147–
149 ꢁC; Rf = 0.38 (CHCl3:MeOH/NH4OH, 85:10:5);
IR (KBr) 3302 (CONH str), 2929 (CH), 1728
(CH3CO), 1643 (CONH), 1551 (NHd), 1246 (C–O),
1
1038 cmꢀ1; H NMR (300 MHz, CDCl3): d 0.78 (3H,
s, 18-CH3), 1.11 (3H, s, 19-CH3), 1.18 (3H, d, J = 7,
21-CH3), 1.40 (12H, s, 25-CH2, 26-CH2, 27-CH2, 28-
CH2, 29-CH2, 30-CH2), 1.48–2.10 (19H, 7· CH2,
5· CH), 2.13 (3H, s, 20-CH3), 2.41 (2H, d, J = 7, 4-
CH2), 2.77 (2H, t, J = 7, 31-CH2), 3.28 (2H, m, 24-
CH2), 4.69 (1H, m, 3-CH), 5.47 (1H, d, J = 5, 6-CH),
5.53 (1H, m, 23-NH); 13C NMR (75 MHz, CDCl3): d
12.5 (18-CH3), 18.1 (21-CH3), 19.7 (19-CH3), 21.4
(11-CH2), 21.9 (20-CH3), 24.7 (CH2), 27.2 (CH2), 27.3
(CH2), 28.0 (CH2), 28.1 (CH2), 29.7 (CH2), 29.8
(CH2), 30.1 (CH2), 31.3 (CH), 32.2 (CH2), 32.3 (CH),
34.2 (CH2), 37.0 (10-C), 37.4 (CH2), 38.5 (CH2), 39.6
(CH2), 39.9 (CH2), 42.7 (13-C), 45.4 (20-CH), 50.3 (9-
CH), 52.0 (31-CH2), 53.2 (17-CH), 56.6 (14-CH), 74.3
(3-CH), 122.9 (6-CH), 140.0 (5-C), 170.9 (10-C@O),
176.9 (22-C@O); MS (ES+) m/z (rel intensity) 515
(M+, 100); HRMS calcd for C32H55N2O3 ([M + H]+):
515.4213; found: 515.4199. Anal. Calcd for
C32H54N2O3Æ1.01H2O: C, 72.1; H, 10.6; N, 5.3; Found:
C, 72.1; H, 10.3; N, 4.8.
5.2.6. Bis-3b-Acetoxy-23,24-bisnor-chol-5-en-22-oxo-22-
(1,6)-diaminohexyl (4f). Compound 4f (0.163 g, white
solid) was obtained as by-product during the synthesis
of the compound 4b by procedure A: mp 264–266 ꢁC;
Rf = 0.42 (5% MeOH/CHCl3); 1H NMR (300 MHz,
CDCl3): d 0.81 (6H, s, 18-CH3), 1.13 (6H, s, 19-CH3),
1.30 (6H, d, J = 7, 21-CH3), 1.36–2.12 (46H: 18· CH2,
10· CH), 2.15 (6H, s, 20-CH3), 2.43 (4H, d, J = 7, 4-
CH2), 3.34 (4H, m, 24-CH2), 4.68 (2H, m, 3-CH), 5.49
(2H, d, J = 5, 6-CH), 5.77 (2H, m, 23-NH); 13C NMR
(75 MHz, CDCl3): d 12.5 (18-CH3), 18.2 (21-CH3),
19.7 (19-CH3), 21.4 (11-CH2), 21.9 (20-CH3), 24.8
(CH2), 26.0 (CH2), 28.0 (CH2), 28.1 (CH2), 29.9
(CH2), 32.2 (CH2), 32.3 (CH2), 37.0 (10-C), 37.4
(CH2), 38.5 (CH2), 38.8 (CH2), 39.0 (CH2), 39.9
(CH2), 42.7 (13-C), 45.3 (20-CH), 50.3 (9-CH), 53.2
(17-CH), 56.7 (14-CH), 74.3 (3-CH), 122.9 (6-CH),
140.0 (5-C), 170.9 (10-C@O), 177.1 (22-C@O); MS
(ES+) m/z (rel intensity) 879 (M+Na+, 100); HRMS
calcd for C54H85N2O6 ([M + H]+): 857.6407; found:
857.6415.
5.2.4.
3b-Acetoxy-23,24-bisnor-chol-5-en-22-oxo-22-
(1,10)-diaminodecyl (4d). 0.430 g, 62% yield; mp 153–
155 ꢁC; Rf = 0.44 (CHCl3:MeOH/NH4OH, 85:10:5); IR
(KBr) 3289 (CONH str), 2927 (CH), 1728 (CH3CO),
1642 (CONH), 1557 (NHd), 1462 (CH2), 1248 (C–O
1
str), 1036 cmꢀ1; H NMR (300 MHz, CDCl3): d 0.67
(3H, s, 18-CH3), 1.00 (3H, s, 19-CH3), 1.16 (3H, d,
J = 7, 21-CH3), 1.26 (16H, s, 25-CH2, 26-CH2, 27-
CH2, 28-CH2, 29-CH2, 30-CH2, 31-CH2, 32-CH2),
1.37–1.99 (19H: 7· CH2, 5· CH), 2.01 (3H, s, 20-CH3),
2.30 (2H, d, J = 7, 4-CH2), 2.65 (2H, t, J = 7, 33-CH2),
3.20 (2H, m, 24-CH2), 4.58 (1H, m, 3-CH), 5.35 (1H,
d, J = 4, 6-CH), 5.44 (1H, m, 23-NH); 13C NMR
(75 MHz, CDCl3): d 12.5 (18-CH3), 18.1 (21-CH3),
19.7 (19-CH3), 21.4 (11-CH2), 21.9 (20-CH3), 24.7
(CH2), 27.3 (CH2), 28.0 (CH2), 28.1 (CH2), 29.7
(CH2), 29.8 (CH2), 29.9 (CH2), 30.1 (CH2), 32.2
(CH2), 32.3 (CH2), 34.2 (CH2), 37.0 (10-C), 37.4
(CH2), 38.5 (CH2), 39.6 (CH2), 39.9 (CH2), 42.7 (13-
C), 45.4 (20-CH), 50.3 (9-CH), 53.2 (17-CH), 56.6 (14-
CH), 74.3 (3-CH), 122.9 (6-CH), 140.0 (5-C), 171.0
(10-C@O), 176.9 (22-C@O); MS (ES+) m/z (rel intensity)
543 (M+, 100); HRMS calcd for C34H59N2O3
([M + H]+): 543.4526; found: 543.4522 (M + H+). Anal.
Calcd for C34H58N2O3Æ0.42 H2O: C, 74.2; H, 10.8; N,
5.1; Found: C, 74.2; H, 10.6; N, 4.8.
5.2.7. Bis-3b-acetoxy-23,24-bisnor-chol-5-en-22-oxo-22-
(1,8)-diaminooctyl (4g). Compound 4g (0.241 g, white
solid) was obtained as by-product during the synthesis
of the compound 4c by procedure A: mp 238 ꢁC;
Rf = 0.54 (5% MeOH/CHCl3); 1H NMR (300 MHz,
CDCl3): d 0.64 (6H, s, 18-CH3), 0.97 (6H, s, 19-CH3),
1.13 (6H, d, J = 7, 21-CH3), 1.25 (12H, s, 25-CH2, 26-
CH2, 27-CH2), 1.34–1.92 (38H, 14· CH2, 10· CH),
1.99 (6H, s, 20-CH3), 2.27 (4H, d, J = 7, 4-CH2), 3.16
(4H, m, 24-CH2), 4.56 (2H, m, 3-CH), 5.33 (4H, m,
6-CH, 23-NH); 13C NMR (75 MHz, CDCl3): d 12.5
(18-CH3), 18.1 (21-CH3), 19.7 (19-CH3), 21.4 (11-
CH2), 21.9 (20-CH3), 24.8 (CH2), 27.1 (CH2), 28.0
(CH2), 28.1 (CH2), 29.4 (CH2), 30.0 (CH2), 32.2 (CH2),
32.3 (CH2), 37.0 (10-C), 37.4 (CH2), 38.5 (CH2), 39.0
(CH2), 39.6 (CH2), 39.9 (CH2), 42.7 (13-C), 45.4