826
F.-W. Liu et al. / Steroids 70 (2005) 825–830
Table 1
2.2. 3β-Chloro-androst-5-en-17-one (2) and
bis-(3β-androst-5-en-17-one) ether (3)
Selected 1H NMR data of compound 2–8
H
2
3
4
5
6
7
8
Anhydrous FeCl3 (85 mg, 0.52 mmol) was added at room
temperature into a stirring solution of DHEA (1, 150 mg,
0.52 mmol) in dry CH2Cl2 (5 mL). After the disappearance
of 1 as detected by TLC monitoring (5 h) by using 10:1
petrol ether–EtOAc, H2O (2 mL) was added to the mixture.
The organic layer was separated and dried over anhydrous
Na2SO4, followed by fractionation by chromatography with
15:1 petrol ether–EtOAc, to afford 2 (115 mg, 72% yield),
along with a 13% yield of by-product 3.
3
6
4
18
19
16
17
3.77
5.41
2.52
0.89
1.06
3.29
5.37
2.25
0.89
1.03
3.77
5.37
2.54
0.67
1.03
3.76
5.37
2.53
0.63
1.03
3.76
5.38
2.53
0.92
1.03
6.71
3.76
5.37
2.54
0.79
1.05
4.41
1.78
3.77
5.37
2.54
0.80
1.06
MOD 1106 analyzer. Infrared spectra were recorded on a
Thermo Nicolet 200 spectrometer using KBr disks in the
400–4000 cm−1 region. Melting-points were measured on a
WC-1 melting-point apparatus and are uncorrected. Survey
spectra(including1HNMR, 13CNMR, homonuclearcorrela-
tion (COSY), heteronuclear single quantum coherence spec-
(HMBC), and DEPT) were obtained on a Bruker DPX-400
instrument with Me4Si as the internal standard. Chemical
shifts are given in δ values. Selected 1H and 13C NMR
spectral data are reported in Table 1 and 2. High-resolution
mass spectra were recorded with a Q-TOF micro mass
spectrometer.
2.2.1. 3β-Chloro-androst-5-en-17-one (2)
mp 151–152 ◦C, [α]D20 +10.0◦ (c 0.28, CHCl3). IR (KBr):
2947, 2860, 1734 cm−1. HRMS: Calcd. for C19H27ClO: m/z
306.1750 [M]+. Found: m/z 329.1648 [M + Na]+, 331.1618
[M + 2 + Na]+. Anal. Calcd. for C19H27ClO: C, 74.36; H,
8.87. Found: C, 74.67; H, 8.82.
Crystal data: C19H27ClO, M = 306.86, Monoclinic,
◦
˚
a = 6.5364(13), b = 7.6371(15), c = 17.067(3) A, α = 90 ,
3
β = 96.77(3)◦, γ = 90◦, V = 846.0(3) A , T = 291(2) K,
˚
space group P2(1), Z = 2, D = 1.205 Mg m−3
, µ(Mo
K␣) = 0.224 mm−1, θ range 1.20–27.48, F(000) = 332, 3061
reflection collected, 2938 unique [R(int) = 0.0236], final R
indices [I > 2(I)]: R1 = 0.0510, wR2 = 0.1264, R indices (all
data): R1 = 0.0660, wR2 = 0.1341.
X-ray crystal analysis was made on a Rigaku RAXIS-IV
imaging plate with graphite monochromated Mo K␣ radi-
ation (λ = 0.71073 A). The structure was solved by direct
˚
non-hydrogen atoms were refined with anisotropic thermal
parameters. All hydrogen atoms were refined isotropically.
All calculations were performed using the SHELX-97 crys-
tallographic software package [19].
2.2.2. Bis-(3β-androst-5-en-17-one) ether (3)
mp 268–269 ◦C, [α]D20 +16.0◦ (c 0.20, CHCl3). IR
(KBr): 2935, 2897, 2860, 1736, 1094 cm−1. HRMS: Calcd.
for C38H54O3: m/z 558.4073 [M]+. Found: m/z 581.3965
[M + Na]+. Anal. Calcd. for C38H54O3: C, 81.67; H, 9.74.
Found: C, 81.88; H, 9.52.
Table 2
2.3. 3β-Chloro-5-cholestene (4)
Selected 13C NMR data of compound 2–8
C
2
3
4
5
6
7
8
Using the same method as described above, 5-cholesten-
3-ol (cholesterol, 150 mg, 0.39 mmol) was treated with
anhydrous FeCl3 (63 mg, 0.39 mmol) to give 4 (109 mg,
69%): mp 90–91 ◦C, [α]D20 −32.5◦ (c 0.35, CHCl3). IR (KBr):
2940, 2861, 1464, 1378 cm−1. HRMS: Calcd. for C27H45Cl:
m/z 404.3210 [M]+. Found: m/z 427.3112 [M + Na]+,
429.3095[M + 2 + Na]+. Anal. Calcd. forC27H45Cl:C, 80.05;
H, 11.20. Found: C, 79.89; H, 11.36.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
39.0
33.3
60.0
43.3
39.9
29.7
76.2
37.3
39.1
33.4
60.4
43.4
38.7
33.3
60.1
43.3
34.6
33.3
60.1
43.4
39.0
33.3
60.2
43.3
39.1
33.3
60.1
43.3
141.1
121.7
31.4
31.4
50.2
36.5
20.3
30.7
47.5
51.7
21.9
35.8
220.9
13.5
19.3
141.5
120.6
31.4
31.4
50.3
36.9
20.3
30.8
47.5
51.7
21.9
35.8
221.3
13.5
19.4
140.8
122.5
31.9
31.8
50.1
36.4
21.0
39.7
42.3
56.7
24.3
28.2
56.2
11.9
19.3
35.8
18.7
140.8
122.2
31.7
31.7
49.9
36.4
20.9
39.1
43.9
56.8
24.4
22.8
63.7
13.2
19.2
209.4
31.5
141.4
121.8
31.5
30.1
50.4
36.6
20.5
39.0
46.1
56.4
32.2
144.3
155.3
15.7
19.2
196.8
27.1
140.8
122.2
31.9
31.3
49.9
36.5
20.7
39.7
40.2
56.4
31.8
80.8
62.0
16.3
19.3
41.6
14.5
140.9
122.1
31.6
31.4
50.0
36.4
20.4
36.7
42.3
51.0
23.5
27.5
82.7
11.9
19.3
2.4. 3β-Chloro-5-pregnen-20-one (5)
Following the same procedure as in Section 2.2, 3-
hydroxy-5-pregnen-20-one (120 mg, 0.38 mmol) was treated
with anhydrous FeCl3 (62 mg, 0.38 mmol) to furnish 5
(93 mg, 73%): mp 85–86 ◦C, [α]D20 +33.5◦ (c 0.46, CHCl3).
IR (KBr): 2923, 2853, 1745, 1232, 1039 cm−1. HRMS:
Calcd. for C21H31ClO: m/z 334.2063 [M]+. Found: m/z
357.1955 [M + Na]+, 359.1946 [M + 2 + Na]+. Anal. Calcd.
for C21H31ClO: C, 75.31; H, 9.33. Found: C, 75.11; H, 9.45.