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A. Iuliano, A. Ruffini / Tetrahedron: Asymmetry 16 (2005) 3820–3828
under nitrogen atmosphere just before use. N-Bromo-
succinimide was recrystallized from water. 3-Mercapto-
propyltrimethoxysilane was distilled under reduced
pressure before use. Unless otherwise specified, the
reagents were used without any purification. Compounds
6 and 12 were synthesized as previously reported and
matched the reported characteristics.5
4.4. N-Allyl-N0-methyl-3-acetyl-7-hydroxy-12-(3,5-di-
nitrophenyl)carbamoyloxycholan-24-amide, 9
Compound 8 (1.6 g, 2.2 mmol) was dissolved in a mix-
ture of dry THF (4 mL) and methanol (20 mL) cooled
to 0 ꢁC, and NaBH4 (0.14 g, 3.7 mmol) added slowly.
When gas evolution ceased, the mixture was allowed
to warm to room temperature and stirred overnight.
The solvent was removed at reduced pressure, and the
remaining solid dissolved in ethyl acetate. The solution
was washed with 10% KHCO3 (2 · 30 mL) and brine
(2 · 30 mL), then dried over anhydrous Na2SO4. After
removing the solvent under reduced pressure, the crude
product was purified by flash chromatography (SiO2,
4.2. N-Allyl-N0-methyl-3-acetyl-7-oxo-12-hydroxy-
cholan-24-amide, 7
Acetic anhydride (2.05 mL, 21.7 mmol) in dry toluene
(3.15 mL) was added to a solution of amide 6 (3 g,
6.5 mmol) in dry toluene (3.15 mL) and the resulting
mixture was stirred for 5 h at 80 ꢁC, then cooled to
room temperature and diluted in CH2Cl2. The solvent
was removed under reduced pressure and the crude
product purified by flash chromatography (SiO2,
CH2Cl2–acetone = 80:20) affording 9 (1.3 g, 1.8 mmol,
22
81%): mp = 135–142 ꢁC; ½aꢀD ¼ þ56:4 (c 0.99, CH2Cl2);
1H NMR (200 MHz, CDCl3, d): 0.76 (s, 3H, CH3); 0.89
(s, 3H, CH3); 0.96–2.40 (m, 28H, CH and CH2 steroidal
and OH 7); 2.16 (s, 3H, OCOCH3); 2.88 and 2.92 (s,
3H, N–CH3); 3.80–4.01 (m, 3H, CH2–CH@CH2 and
CH 7); 4.51 (m, 1H, CH 3); 5.05–5.20 (m, 3H,
CH2@CH and CH 12); 5.67 (ddt, 1H, CH@CH2); 8.66
(t, 1H, aromatic); 8.76 (d, 2H, aromatics); 9.08 (d,
1H, NH carbamate); 13C NMR (50 MHz, CDCl3, d):
12.1, 17.8, 21.3, 22.4, 22.9, 25.6, 26.6, 27.4, 27.6, 30.8,
34.6, 35.1, 38.4, 39.0, 41.0, 43.4, 45.2, 47.7, 50.1, 52.2,
68.0 (C 7), 74.3 (C 12), 78.5 (C 3), 112.2, 116.7
(@CH2), 118.0, 132.7 (ACH@), 141.4, 148.8, 152.8
(C@O carbamate), 170.6 (C@O acetyl). IR (KBr,
cmꢁ1): 3854, 3821, 3751, 3736, 3712, 3689, 3676, 3650,
3447, 3115, 2941, 2872, 2346, 1734, 1624, 1548, 1466,
1424, 1344, 1246, 1224, 1193, 1075, 1025, 1009, 897,
806, 769, 732, 656, 611, 400.
CH2Cl2–acetone = 75:25) affording 7 (1.7 g, 3.4 mmol,
20
52%): mp = 74–78 ꢁC; ½aꢀD ¼ þ17:3 (c 0.99, CH2Cl2);
1H NMR (200 MHz, CDCl3, d): 0.67 (s, 3H, CH3);
0.96 (d, 3H, CH3 21); 1.17 (s, 3H, CH3); 0.90–2.50
(m, 28H, CH and CH2 steroidal, OH 12); 2.16 (s, 3H,
OCOCH3); 2.89 and 2.93 (s, 3H, N–CH3); 3.87–3.98
(m, 3H, CH2ACH@CH2 and CH 12); 4.66 (m, 1H,
CH 3); 5.06–5.28 (m, 2H, CH2@CH); 5.75 (ddt, 1H,
CH@CH2); 13C NMR (50 MHz, CDCl3, d): 12.8,
17.6, 21.2, 22.7, 24.1, 25.8, 27.5, 29.1, 33.0, 33.6, 34.6,
34.9, 35.9, 40.7, 45.1, 45.7, 46.5, 49.4, 72.0 (C 12),
72.8 (C 3), 170.5 (C@O acetyl), 211.0 (C@O carbony-
lic). IR (KBr, cmꢁ1): 3813, 3440, 2948, 1732, 1709,
1629, 1468, 1392, 1364, 1244, 1080, 1049, 924, 802,
597, 400.
4.3. N-Allyl-N0-methyl-3-acetyl-7-oxo-12-(3,5-dinitro-
phenyl)carbamoyloxycholan-24-amide, 8
4.5. N-Allyl-N0-methyl-3-acetyl-7-(2-naphthyl)carba-
moyloxy-12-(3,5-dinitrophenyl)carbamoyloxycholan-24-
amide, 10
3,5-Dinitrophenylisocyanate (1.21 g, 5.8 mmol) was
added to a solution of 7 (1.5 g, 3.0 mmol) in dry toluene
(45 mL) and the resulting mixture heated at reflux and
stirred overnight, then allowed to cool to room temper-
ature. The solvent was removed under reduced pressure
and the crude product purified by flash chromatography
2-Naphthylisocyanate (0.65 g, 3.6 mmol) and DMAP
(0.14 g, 1.1 mmol) were added to a solution of 9 (1.2 g,
1.7 mmol) in dry toluene (40 mL) and the resulting mix-
ture heated at reflux and stirred for 24 h, then filtered to
remove 2-naphthylurea; the solvent was evaporated
under reduced pressure and the obtained solid purified
by flash chromatography (SiO2, CH2Cl2–ethyl acetate =
(SiO2, CH2Cl2–acetone = 92:8) affording
8
(1.7 g,
21
2.4 mmol, 80%): mp = 138–145 ꢁC; ½aꢀD ¼ þ63:1 (c 1,
1
CH2Cl2); H NMR (200 MHz, CDCl3, d): 0.67 (s, 3H,
85:15) to afford 10 (1.1 g, 1.2 mmol, 74%): mp = 144–
23
CH3); 0.96 (d, 3H, CH3 21); 1.17 (s, 3H, CH3); 0.90–
2.50 (m, 27H, CH and CH2 steroidal); 2.16 (s, 3H,
OCOCH3); 2.89 and 2.96 (s, 3H, N–CH3); 3.85–4.01
(m, 2H, CH2–CH@CH2); 4.63 (m, 1H, CH 3); 5.04–
5.28 (m, 3H, CH2@CH and CH 12); 5.71 (ddt, 1H,
CH@CH2); 8.65 (t, 1H, aromatic); 8.76 (d, 2H, aromat-
ics); 9.06 (d, 1H, NH carbamate); 13C NMR (50 MHz,
CDCl3, d): 12.4, 17.8, 21.2, 22.7, 23.9, 25.9, 26.4, 27.6,
30.2, 30.9, 31.3, 33.1, 33.5, 33.8, 34.6, 35.1, 36.8, 38.4,
42.0, 45.1, 45.2, 45.7, 46.6, 46.9, 48.9, 50.3, 52.3, 72.9
(C 3), 112.1, 116.9 (@CH2), 117.2, 117.9, 132.4
(ACH@), 141.5, 146.5, 148.7, 152.9 (C@O carbamate),
170.4 (C@O acetyl), 173.5, 174.0 (C@O amide), 211.0
(C@O carbonylic). IR (KBr, cmꢁ1): 3854, 3838, 3751,
3244, 3117, 2956, 2364, 2345, 1734, 1710, 1654, 1617,
1546, 1466, 1424, 1345, 1245, 1222, 1066, 1048, 1022,
919, 897, 806, 765, 732, 669, 656, 400.
148 ꢁC; ½aꢀD ¼ þ87:1 (c 0.97, CH2Cl2); 1H NMR
(200 MHz, CDCl3, d): 0.76 (s, 3H, CH3); 0.86 (d,
3H, CH3 21), 0.93 (s, 3H, CH3); 0.96–2.40 (m, 27H,
CH and CH2 steroidal); 2.03 (s, 3H, OCOCH3);
2.83 and 2.87 (s, 3H, N–CH3); 3.73–3.95 (m, 2H,
CH2–CH@CH2); 4.52 (m, 1H, CH 3); 4.90–5.14 (m,
4H, CH2@CH and CH 12 and CH 7); 5.63 (ddt, 1H,
CH@CH2); 7.25–7.80 (m, 9H, H naphthylics and NH
carbamates), 8.01–8.70 (m, 3H, aromatics); 13C NMR
(50 MHz, CDCl3, d): 12.1, 14.1, 17.6, 20.9, 21.1, 22.4,
22.8, 25.7, 26.8, 27.3, 29.1, 30.1, 30.6, 31.3, 33.5, 34.3,
34.9, 35.0, 37.8, 40.6, 43.8, 45.4, 47.4, 50.1, 52.2, 72.0
(C 7), 73.9 (C 12), 78.4 (C 3), 112.0, 114.7, 116.9
(@CH2), 117.6, 117.9, 119.2, 124.6, 126.3, 127.2, 127.4,
128.7, 130.0, 132.1, 133.8 (ACH@), 135.4, 141.3, 141.4,
148.6, 152.9 (C@O carbamate), 153.1 (C@O carbamate),
167.7, 170.3 (C@O acetyl), 173.7, 174.0 (C@O amide).