9566
M.S. Bjelakovi´c et al. / Tetrahedron 65 (2009) 9557–9568
a SiO2 column (400 g). Elution with PhMe/Et2O 95:5 gave 2.88 g
(65%) of pure
14-3,5-diol 3-acetate 2, which was used in the next
step without further purification: Rf¼0.80 (PhMe/EtOAc 9:1); mp
1737, 1274, 1254, 1031; 1H NMR (500 MHz, C6D6):
J¼6.0, H-3), 3.09 (s, C(5)–OH), 2.48 (s, C(14)–OH), 2.30 (m, 1H, H
16), 2.14 (m, 1H, H-17), 2.11 (m, 1H, H-9), 2.06 (m, 1H, H -7), 2.05
(m, 1H, H -12), 1.94 (m, 1H, H -2), 1.90 (m, 1H, H -4), 1.82 (s, AcO),
1.82 (m, 1H, H -1), 1.70 (m, 1H, H -12), 1.68 (m, 2H, H-8, H -4), 1.64
(m, 1H, H-22), 1.62 (m, 1H, H-25), 1.60 (m, 1H, H -2), 1.58 (m, 1H,
-15), 1.57 (m, 1H, H-23), 1.53 (m, 1H, H -6), 1.49 (m, 1H, H-20),
1.42 (m, 1H, H -15), 1.34 (m, 3H, H -1, H -11, H -16), 1.33 (m, 1H,
-6), 1.31 (m, 2H, H-23, H-24), 1.25 (m, 1H, H -11), 1.22 (m, 1H, H-
d 5.46 (hept.,
D
a-
a
20
144 ꢁC (from acetone); [
1277, 1240, 1032; 1H NMR (400 MHz, CDCl3):
15), 2.28 (ddd, 1H, J¼2.8, 7.5, 16.0, 1H, H-16), 2.08 (m, 1H, H
2.08 (s, AcO), 2.02 (m, 1H, H -12), 1.91 (m, 2H, H -2, H-16), 1.76 (m,
1H, H -6), 1.72 (m, 2H, H2-4), 1.70 (m, H, H -7), 1.61 (m, 1H, H -1),
1.60 (m, 1H, H -2), 1.56 (m, 1H, H-20), 1.54 (m, 1H, H-25), 1.53 (m,
1H, H-17), 1.50 (m, 1H, H -1), 1.48 (m, 1H, H -11), 1.37 (m, 1H, H-
22),1.36 (m, 2H, H -7, H-23),1.33 (m,1H, H-9),1.32 (m, 2H, H-8, H
11), 1.31 (m, 1H, H -12), 1.19 (m, 1H, H-23), 1.16 (m, 1H, H-24), 1.06
a
]
þ17 (c 0.1, CHCl3); IR: nmax 3455, 1734,
a
a
a
D
d
5.17 (s, 2H, H-3, H-
-6),
a
b
b
b
b
b
a
H
a
b
a
a
a
a
b
a
b
b
H
a
b
b
a
22), 1.08 (d, J¼6.0, 3H, CH3-21), 0.98, 0.99 (2d, J¼6.5, 6H, CH3-26,
b
b
-
CH3-27), 0.83 (s, 3H, CH3-19), 0.80 (s, 3H, CH3-18); 13C NMR
a
(125 MHz, C6D6): d 170.8 (s, AcO), 86.0 (s, C-14), 75.6 (s, C-5), 71.4 (d,
(m, 1H, H-22), 1.01 (s, 3H, CH3-19), 0.91 (d, 3H, CH3-21, J¼6.8), 0.90s
C-3), 51.9 (d, C-17), 47.5 (s, C-13), 40.8 (t, C-4), 40.4 (t, C-24), 39.4 (s,
C-10), 38.7 (d, C-9), 38.5 (d, C-8), 37.5 (t, C-22), 36.9 (d, C-20), 34.9
(t, C-6), 33.8 (t, C-15), 33.3 (t, C-12), 31.9 (t, C-1), 28.8 (d, C-25), 28.3
(t, C-16), 27.9 (d, C-2), 25.4 (t, C-23), 23.5, 23.2 (two q, C-27 and C-
26), 21.5 (q, AcO), 21.4 (t, C-7), 21.3 (t, C-11),19.4 (q, C-21),16.6 (q, C-
(CH3-18), 0.87 (d, 6H, CH3-26, CH3-27, J¼6.8); 13C NMR (100 MHz,
CDCl3):
d 170.6 (s, AcO), 154.9 (s, C-14), 117.2 (d, C-15), 74.7 (s, C-5),
70.8 (d, C-3), 58.7 (d, C-17), 47.1 (s, C-13), 45.4 (d, C-9), 42.2 (t, C-12),
40.0 (t, C-4), 39.5 (t, C-24), 38.9 (s, C-10), 36.0 (t, C-22), 35.6 (t, C-
16), 34.1 (d, C-8), 34.0 (t, C-6), 33.9 (d, C-20), 30.5 (t, C-1), 28.0 (d, C-
25), 26.7 (t, C-2), 23.8 (t, C-7), 23.7 (t, C-23), 22.8, 22.5 (two q, C-26
and C-27), 22.0 (t, C-11), 21.4 (q, AcO), 18.9 (q, C-21), 16.9 (q, C-18),
18), 16.3 (q, C-19); 2D NOESY correlations H-3/H
a
-4, H
-11, H
-11; CH3-21/H-20, Hb-
a
-2, C(5)–
OH; H-9/C(5)–OH, C(14)–OH; CH3-18/H-8, H-20, H
b
b-15, CH3-
21; CH3-19/H-8, H
b-2, H
b
-4, H
b
-6, H
b-1, H
b
15.8 (q, C-19); 2D NOESY correlations H-3/H
a-4, H
a
-2, Ha
-1; H-15/
12; ESI-TOF–MS: m/z: calcd for C30H51O6: 507.36911 [MþHCOO]ꢀ,
H
a
,
b
-16; CH3-18/H-8, H
b
-11; CH3-19/H-8, H
b
-2, Hb-4, Hb
-6, H -11;
b
found 507.36765.
ESI-TOF–MS: m/z: calcd for C29H48O3Na: 467.34957 [MþNa]þ,
found 467.34620.
4.5. Hypoiodite HgO oxidation of 4
4.3. 14
a,15-Epoxycholestane-3
b,5a
-diol 3-acetate (3)7
A stirred suspension of 5a,14a-diol 4 (500 mg, 1.08 mmol), yel-
low HgO (1.400 g, 6.48 mmol), and I2 (2.822 g, 11.12 mmol) in dry
CCl4 (350 ml) was irradiated with an 800 W OSRAM Halogen-Bel-
laphot lamp (at 100 V) at room temperature for 4 h. The mixture
was filtered, the filtrate washed successively with aq Na2S2O3 soln,
aq NaHCO3 soln, and H2O, dried (Na2SO4), evaporated, and the
resulting mixture separated by FCC, PhMe/EtOAc (0/20).
To a stirred solution of 2 (2.80 g, 6.30 mmol) in CH2Cl2 (50 ml)
m-chloroperbenzoic acid (1.52 g, 8.82 mmol) was added, and the
mixture left at room temperature for 1 h. The reaction mixture was
worked up as usually. The crude product was crystallized from
acetone/MeOH to give 2.67 g (92%) of 14
(PhMe/EtOAc 9:1); mp 146–147 ꢁC (from MeOH/acetone); [
(c 0.1, CHCl3); IR: nmax 3507, 1737, 1268, 1251, 1030; 1H NMR
(500 MHz, C6D6):
5.51 (hept., J¼6.0, 1H, H-3), 3.19 (s, 1H, H-15),
2.11 (dd, J¼6.5, 13.0, 1H, H -16), 1.98 (m, 3H, H -2, H-8, H-9), 1.82
(m, 1H, H -12), 1.79 (m, 1H, H -1), 1.78 (s, 3H, AcO), 1.78 (m, 1H, H
4), 1.76 (m, 1H, H -7), 1.66 (m, 1H, H -12), 1.63 (m, 1H, H -4), 1.58
(m, 1H, H -2), 1.53 (m, 1H, H-25), 1.44 (m, 1H, H -6), 1.39 (m, 1H, H-
17), 1.38 (m, 1H, H -11), 1.37 (m, 1H, H-23), 1.36 (m, 1H, H-22), 1.33
(m,1H, H-20),1.29 (m,1H, H -1),1.20 (m,1H, H -11),1.17 (m, 2H, H-
23, H-24), 1.10 (m, 1H, H -16), 1.02
-6), 1.03 (dd, J¼10.0, 13.0, 1H, H
(m, 1H, H-22), 0.919, 0.922 (2d, J¼6.5, 6H, CH3-26, CH3-27), 0.89 (m,
1H, H
-7), 0.89 (d, J¼6.5, 3H, CH3-21), 0.82 (s, 3H, CH3-19), 0.74 (s,
3H, CH3-18); 13C NMR (125 MHz, C6D6):
170.3 (s, AcO), 74.3 (s, C-
a
,15
a
-epoxide 3: Rf¼0.20
20
a
]
þ10
Elution with PhMe/EtOAc 95:5 gave the (Z)-5-oxo-5,10-seco-
D
cholest-1(10)-ene-3
(PhMe/EtOAc 8:2); mp 162–163 ꢁC (from MeOH/acetone); [
a]
D
b
,14
a
-diol 3-acetate (5) (49.8 mg, 10%): Rf¼0.64
20
d
a
a
þ61.9 (c 0.1163, CHCl3); IR: nmax 3577, 3510, 1732, 1699, 1656, 1466,
1441, 1376, 1240, 1031; 1H and 13C NMR (400 and 100 MHz, C6D6)
see Table 1; MS: 460 (Mþ), 400 (Mþꢀ60), 382 (Mþꢀ60–18).
Elution with PhMe/EtOAc 90:10 gave the (E)-5-oxo-5,10-seco-
b
a
a-
a
a
b
b
b
a
cholest-1(10)-ene-3
(PhMe/EtOAc 8:2); mp 127–128 ꢁC (from MeOH/acetone); [
a]
D
b
,14
a
-diol 3-acetate (6) (264 mg, 53%): Rf¼0.49
20
b
b
a
b
þ27.3 (c 0.1247, CHCl3); IR: nmax 3581, 3520, 1725, 1699, 1656, 1464,
1368, 1256, 1034; 1H and 13C NMR (400 and 100 MHz, C6D6) see
Table 1; MS: 442 (Mþꢀ18), 400 (Mþꢀ60).
b
d
Further elution with PhMe/EtOAc 88:12 afforded 1R,10R-epoxy-
5), 73.9 (s, C-14), 71.4 (d, C-3), 58.0 (d, C-15), 49.4 (d, C-17), 42.7 (d,
C-9), 41.8 (s, C-13), 40.8 (t, C-4), 40.3 (t, C-24), 39.4 (s, C-10), 36.6 (t,
C-22), 36.5 (t, C-12), 34.6 (d, C-20), 34.1 (t, C-6), 32.8 (t, C-16), 32.0
(d, C-8), 31.2 (t, C-1), 28.7 (d, C-25), 27.8 (t, C-2), 24.7 (t, C-23), 23.4,
23.1 (two q, C-27 and C-26), 21.8 (t, C-11), 21.5 (q, AcO), 20.3 (t, C-7),
19.4 (q, C-21), 16.2 (q, C-19), 15.1 (q, C-18); 2D NOESY correlations
5-oxo-5,10-secocholestane-3b,14a-diol 3-acetate (7) (31 mg, 6.0%):
Rf¼0.40 (PhMe/EtOAc 8:2); mp 181–182 ꢁC (from MeOH/acetone);
20
[a
]
þ32.0 (c 0.1156, CHCl3); IR: nmax 3521, 1726, 1462, 1380, 1261,
D
1127, 1031; 1H and 13C NMR (400 and 100 MHz, CDCl3) see Table 1;
MS: 476 (Mþ), 458 (Mþꢀ18), 416 (Mþꢀ60), 398 (Mþꢀ60–18).
H-3/H
12, H-20, H
a
-4, H
a
-2; H-15/H
a
,
b
-7, H
a
,
b
-16; H-8/H
b
-7; CH3-18/H-8, H
b
-
4.5.1. X-ray analysis of 5–7. The compounds were recrystallized by
slow evaporation from a mixture acetone/ethanol/hexane for 5;
from ethanol for 6 and from acetone for 7.
b
-11, H -16; CH3-19/H-8, H
b
b
-2, H -4, H
b
b
-6, H -1, H -11;
b
b
H17/Ha-16; ESI-TOF–MS: m/z: calcd for C29H48O4K: 499.31842
[MþK]þ, found 499.31628.
The X-ray intensity data were collected at 120 K for the three
compounds with an MAR345 image plate using Mo
Ka
4.4. Cholestane-3
b,5a
,14
a
-triol 3-acetate (4)7
(
l
¼0.71069Å) radiation. The crystal was chosen, mounted in inert
oil, and transferred to the cold gas stream for flash cooling. The
crystal data and the data collection parameters are summarized in
Table 4. The unit cell parameters were refined using all the collected
spots after the integration process. The data were not corrected for
absorption, but the data collection mode with high redundancy,
partially takes the absorption phenomena into account.
The epoxide 3 (2.50 g, 5.43 mmol) was reduced with LiAlH4
(0.51 g, 13.44 mmol) in dry Et2O (50 ml) at reflux for 48 h. The re-
action mixture was worked up in the usual manner to give
3b,5a,14a-triol (2.26 g), which was acetylated with Ac2O (25 ml) in
anhyd pyridine (20 ml) overnight at room temperature. Usual
workup gave a residue, which was crystallized from acetone to give
The structures were solved by direct methods and refined by
full-matrix least-squares on F2 using SHELXL97.14 All the non-hy-
drogen atoms were refined anisotropically. The hydrogen atoms
1.63 g (65%) 5,14-diol 4: Rf¼0.17 (PhMe/EtOAc 8:2); mp 194–195 ꢁC
20
(from acetone); [
a
]
þ23.64 (c 0.1269, CHCl3); IR: nmax 3495, 3445,
D