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F. Gigante et al. / Bioorg. Med. Chem. 17 (2009) 5950–5961
raphy (CHCl3/MeOH 100:0?90:10) as a yellow sticky solid (0.039 g,
64% yield); Rf = 0.33 (CHCl3/MeOH: 90/10); LRMS, m/z (ES+ mode):
488.3 ([M+H]+, 100%). Anal. Calcd for C30H49NO4ꢃ0.3H2O: C, 73.07;
H, 10.14; N, 2.84. Found: C, 72.79; H, 9.99; N, 2.96. HRMS (ES+ mode),
calculated for C30H50NO4 ([M+H]+): 488.3740; found: 488.3736;
mp = 76–78 °C; 1H NMR (300 MHz, CDCl3): d 0.71 (3H, s, 18-CH3),
0.92 and 0.98 (3H, 2d, J1 = 6.8, J2 = 6.8, 21-CH3), 1.02 (3H, s, 19-CH3),
1.16 (3H, t, J = 7.5, 30-CH3), 0.70–2.10 (21H, 8 ꢂ CH2, 5 ꢂ CH, 20-CH),
2.31 (4H, m, 4-CH2, 20-CH2), 2.40 (3H, m, 22a-CH2 and 26-CH2), 2.62
(2H, m, 24-CH2), 2.79 (1H, m, 22b-CH2), 3.70 (3H, s, 28-CH3), 4.62
(1H, m, 3-CH), 5.38 (1H, m, 6-CH); 13C NMR (75 MHz, CDCl3): d 9.2
(30-CH3), 11.9 and 12.2 (18-CH3), 17.6 and 17.7 (21-CH3), 19.3 (19-
CH3), 21.0 (CH2), 24.1 and 24.3 (CH2), 25.1 and 25.1 (25-CH2), 27.7
and 27.8 (CH2), 27.9 (20-CH2), 28.0 (CH2), 31.8 and 31.9 (CH2), 32.0
(CH), 35.5 (20-CH), 36.4 (26-CH2), 36.6 and 36.6 (10-C), 37.0 (CH2),
38.1 (4-CH2), 39.4 and 39.7 (CH2), 42.3 and 42.5 (13-C), 49.3 and
49.3 (24-CH2), 49.9 and 50.0 (CH), 51.6 (28-CH3), 54.0 and 54.2 (CH),
55.3 (22-CH2), 56.5 and 56.6 (CH), 73.7 (3-CH), 122.5 (6-CH), 139.7
and 139.7 (5-C), 173.9 and 174.1 (10-C@O), 175.2 and 175.4 (27-C@O).
(1H, m, 22b-CH2), 3.69 (3H, s, 28-CH3), 4.61 (1H, m, 3-CH), 5.39
(1H, m, 6-CH); 13C NMR (75 MHz, CDCl3): d 11.9 and 12.2 (18-
CH3), 17.6 and 17.7 (21-CH3), 19.3 (19-CH3), 21.0 (CH2), 22.4 (40-
CH3 and 50-CH3), 24.2 and 24.3 (CH2), 25.2 and 25.2 (25-CH2),
25.8 (30-CH), 27.7 (CH2), 27.8 and 28.0 (CH2), 31.9 (CH2), 32.0
(CH), 35.5 (20-CH), 36.4 (26-CH2), 36.6 (10-C), 37.0 (CH2), 38.2
(4-CH2), 39.4 and 39.7 (CH2), 42.3 and 42.5 (13-C), 43.8 (20-CH2),
49.3 and 49.4 (24-CH2), 50.0 and 50.0 (CH), 51.6 (28-CH3), 54.0
and 54.2 (CH), 54.7 and 55.3 (22-CH2), 56.5 and 56.6 (CH), 73.6
(3-CH), 122.5 (6-CH), 139.7 (5-C), 172.6 (10-C@O), 174.1 (27-C@O).
5.10.4. 3b-Trimethylacetoxy-23,24-bisnorchol-5-en-22-yl-(N-3-
methoxycarbonylpropyl)-amine (17)
Following the general procedure B, starting from a solution of
13 (0.077 g, 0.50 mmol, 3.6 equiv) and TEA (0.070 mL, 0.50 mmol,
3.6 equiv) in MeOH (6.5 mL), 9 (0.059 g, 0.137 mmol) and NaC-
NBH3 (0.31 mL of 1 M solution in THF, 0.31 mmol, 2.3 equiv) were
added and the reaction stirred at room temperature overnight.
Product 17 was collected after extraction and purification by col-
umn chromatography (CHCl3/MeOH 100:0?90:10) as a white so-
lid (0.031 g, 44% yield); Rf = 0.96 (CHCl3/MeOH: 80/20);
mp = 140–145 °C. Anal. Calcd for C32H53O4NꢃH2O: C, 71.59; H,
10.24; N, 2.61. Found: C, 71.51; H, 10.08; N, 2.27. LRMS, m/z (ES+
mode): 516 ([M+H]+, 100%); HRMS (ES+ mode), calculated for
C32H54NO4 ([M+H]+): 516.4053; found: 516.4054; 1H NMR
(300 MHz, CDCl3): d 0.62 (3H, s, 18-CH3), 0.88 and 0.92 (3H, 2d,
J1 = 6.8, J2 = 6.8, 21-CH3), 0.97 (3H, s, 19-CH3), 1.12 (9H, s, 30-CH3,
40-CH3 and 50-CH3), 0.60–1.95 (21H, 8 ꢂ CH2, 5 ꢂ CH), 2.22 (2H,
m, 4-CH2), 2.31 (2H, m, 26-CH2), 2.48–2.63 (3H, m, 22a-CH2 and
24-CH2), 2.72 (1H, m, 22b-CH2), 3.61 (3H, s, 28-CH3), 4.50 (1H, m,
3-CH), 5.31 (1H, m, 6-CH); 13C NMR (75 MHz, CDCl3): d 11.9 and
12.2 (18-CH3), 17.6 and 17.7 (21-CH3), 19.4 (19-CH3), 21.0 (CH2),
24.1 and 24.3 (CH2), 25.0 and 25.0 (25-CH2), 27.2 (30-CH3, 40-CH3
and 50-CH3), 27.7 (CH2), 28.0 (CH2), 31.9 (CH2), 32.0 (CH), 35.4
(20-CH), 36.3 (26-CH2), 36.6 (10-C), 37.0 (CH2), 38.0 (4-CH2), 38.6
(20-C), 39.4 and 39.7 (CH2), 42.3 and 42.5 (13-C), 49.2 (24-CH2),
50.0 and 50.0 (CH), 51.6 (28-CH3), 54.1 and 54.2 (CH), 54.6 (22-
CH2), 56.5 and 56.6 (CH), 73.5 (3-CH), 122.4 (6-CH), 139.8 (5-C),
174.1 (10-C@O), 178.0 (27-C@O).
5.10.2. 3b-Butoxy-23,24-bisnorchol-5-en-22-yl-(N-3-methoxy-
carbonylpropyl)-amine (15)
Following the general procedure B, starting from a solution of 13
(0.051 g, 0.33 mmol, 2.4 equiv) and TEA (0.045 mL, 0.33 mmol,
2.4 equiv) in MeOH (2.1 mL), 7 (0.055 g, 0.14 mmol) and NaCNBH3
(0.23 mL of a 1 M solution in THF, 0.23 mmol. 1.8 equiv) were added
and the reaction stirred at room temperature overnight. Product 15
was recovered asa sticky yellowsolid afterextraction and purification
by column chromatography (CHCl3/MeOH 100:0?90:10), 53% yield
(0.037 g); Rf = 0.39 (CHCl3/MeOH: 90/10); LRMS, m/z (ES+ mode):
502.37 ([M+H]+, 100%). Anal. Calcd for C31H51NO4ꢃ0.5H2O: C, 72.90;
H, 10.26; N, 2.79. Found: C, 72.62; H, 9.97; N, 2.31. HRMS (ES+ mode),
calculated for C31H52NO4 ([M+H]+): 502.3896; found: 502.3893;
mp = 85–88 °C; 1H NMR (300 MHz, CDCl3): d 0.62 (3H, s, 18-CH3),
0.77 and 0.86 (3H, 2d, J1 = 6.9, J2 = 6.9, 21-CH3), 0.94 (3H, t, J = 7.4, 40-
CH3), 1.04 (3H, s, 19-CH3), 0.60–1.90 (23H, 9 ꢂ CH2, 5 ꢂ CH), 2.22
(2H, m, 20-CH2), 2.22 (2H, m, 4-CH2), 2.31 (2H, m, 26-CH2), 2.58–2.82
(4H, m, 22-CH2 and 24-CH2), 3.69 (3H, s, 28-CH3), 4.52 (1H, m, 3-
CH), 5.29 (1H, m, 6-CH); 13C NMR (75 MHz, CDCl3): d 11.9 and 12.2
(18-CH3), 13.6 (40-CH3), 17.5 and 17.7 (21-CH3), 18.6 (30-CH2), 19.3
(19-CH3), 21.0 (CH2), 24.1 and 24.3 (CH2), 24.7 and 24.8 (25-CH2),
27.7 (CH2), 27.8 and 28.0 (CH2), 31.8 and 31.9 (CH2), 31.9 (CH), 35.3
(20-CH), 36.2 (26-CH2), 36.6 (10-C), 36.6 (20-CH2), 37.0 (CH2), 38.3
(4-CH2), 39.4 and 39.6 (CH2), 42.3 and 42.5 (13-C), 49.2 and 49.2
(24-CH2), 50.0 and 50.0 (CH), 51.6 (28-CH3), 54.1 and 54.2 (CH), 54.5
and 55.2 (22-CH2), 56.5 and 56.6 (CH), 73.6 (3-CH), 122.5 (6-CH),
139.7 (5-C), 173.1 (10-C@O), 174.1 (27-C@O).
5.10.5. 3b-Oxalyloxy-23,24-bisnorchol-5-en-22-yl-(N-3-methoxy-
carbonylpropyl)-amine (18)
Following the general procedure B, starting from a solution of
13 (0.044 g, 0.28 mmol, 2.6 equiv) and TEA (0.039 mL, 0.28 mmol,
2.6 equiv) in MeOH (4 mL), 10 (0.047 g, 0.11 mmol) and NaC-
NBH3 (0.23 mL of 1 M solution in THF, 0.23 mmol, 2.1 equiv)
were added and the reaction stirred overnight at room tempera-
ture. Product 18 was collected after extraction and purification
by column chromatography (CHCl3/MeOH 100:0?80:20) as a
yellow sticky solid (0.051 g, 88% yield); Rf = 0.46 (CHCl3/MeOH:
80/20); LRMS, m/z (ES+ mode): 532.7 ([M+H]+, 84%); 1H NMR
(500 MHz, CDCl3): d 0.65 and 0.67 (3H, 2s, 18-CH3), 0.93 (3H,
d, J = 6.6, 21-CH3), 1.18 (3H, s, 19-CH3), 0.60–2.20 (21H,
8 ꢂ CH2, 5 ꢂ CH), 2.25 (2H, m, 4-CH2), 2.36 (2H, m, 26-CH2),
2.51 (5H, m, 20-CH2, 30-CH2 and 22a-CH2), 2.92 (2H, m, 22b-CH2
and 24a-CH2), 3.17 (1H, m, 24b-CH2), 3.60 (3H, s, 28-CH3), 4.51
(1H, m, 3-CH), 5.28 (1H, m, 6-CH); 13C NMR (125 MHz, CDCl3):
d 11.5 and 12.0 (18-CH3), 16.7 and 17.1 (21-CH3), 19.3 and
19.4 (19-CH3), 21.0 and 21.1 (CH2), 22.6 and 22.7 (CH2), 25.8
(25-CH2), 27.5 and 27.7 (CH2), 27.8 (CH2), 28.0 (CH2), 29.7 (20-
CH2), 31.0 (30-CH2), 31.7 and 31.8 (CH2), 31.9 (CH), 33.7 and
33.8 (20-CH), 36.6 (26-CH2), 36.6 (10-C), 37.3 (CH2), 38.4 (4-
CH2), 39.6 and 39.7 (CH2), 41.0 and 42.1 (13-C), 50.1 (24-CH2),
51.8 and 51.9 (28-CH3), 54.5 and 54.6 (CH), 54.7 (22-CH2), 56.7
and 57.0 (CH), 74.0 (3-CH), 122.4 (6-CH), 139.8 (5-C), 172.5
(10-C@O), 173.1 (27-C@O), 175.7 (40-C@O).
5.10.3. 3b-(30-Methylbutoxy)-23,24-bisnorchol-5-en-22-yl-(N-3-
methoxycarbonylpropyl)-amine (16)
Following the general procedure B, starting from a solution of
13 (0.075 g, 0.49 mmol, 3.2 equiv) and TEA (0.068 mL, 0.49 mmol,
3.2 equiv) in MeOH (6.5 mL), 8 (0.064 g, 0.15 mmol) and NaCNBH3
(0.35 mL of 1 M solution in THF, 0.35 mmol, 2.3 equiv) were added
and the reaction stirred overnight at room temperature. Product 16
was collected as a white solid (0.042 g, 53% yield) after extraction
and purification by column chromatography (CHCl3/MeOH
100:0?90:10); Rf = 0.93 (CHCl3/MeOH: 80/20); LRMS, m/z (ES+
mode): 516 ([M+H]+, 100%). Anal. Calcd for C32H53O4Nꢃ0.18HCl:
C, 74.00; H, 10.36; N, 2.70. Found: C, 73.78; H, 10.44; N, 2.56. HRMS
(ES+ mode), calculated for C32H54NO4 ([M+H]+): 516.4053; found:
516.4061; mp = 75–80 °C; 1H NMR (300 MHz, CDCl3): d 0.68 (3H,
s, 18-CH3), 0.89 and 0.96 (3H, 2d, J1 = 6.9, J2 = 6.9, 21-CH3), 0.95
(3H, s, 19-CH3), 0.97 (6H, s, 40-CH3 and 50-CH3), 0.60–2.20 (22H,
8ꢂCH2, 6 ꢂ CH), 2.19 (2H, m, 20-CH2), 2.33 (2H, m, 4-CH2), 2.49
(2H, m, 26-CH2), 2.52–2.73 (3H, m, 22a-CH2 and 24-CH2), 2.78