362
steroids 7 2 ( 2 0 0 7 ) 360–367
6.01–6.08 (2H, m, H-6, H-7), 6.20–6.29 (2H, m, H-2, H-4), 7.09
2.3.5. Reduction with Super-hydride
(1H, d, J = 10.2 Hz, H-1), 13C NMR (CDCl3) ı: 148.1, 133.4, 132.1,
128.9, 128.0, 123.1, 69.1, 56.2, 54.5, 52.8, 43.7, 40.2, 39.8, 37.6,
35.4, 33.6, 29.4, 28.6, 28.0, 24.1, 23.5, 22.8, 20.5, 18.5, 16.6, 12.3,
FABMS: 365.2 (M+H-H2O)+.
(a) Super-hydride 4 equiv.: To a solution of compound 1
(200 mg, 0.52 mmol) in anhydrous THF 8 mL, was added
dropwise Super-hydride (220.3 mg, 2.08 mmol) for 4 h at
room temperature.
Water was added and the solution was extracted with
ethyl acetate. The combined organic layer were dried over
anhydrous MgSO4, filtered, and evaporated under reduced
pressure to afford crude compound. Column chromatogra-
phy on silica gel, eluting with ethyl acetate/n-hexane (1:7)
gave 2 (12 mg, 6%), 4 (27 mg, 14%), and starting material
(117 mg, 59%).
2.4.
Synthesis of 1,4,6-androstatriene-3,17-dione (7)
A solution of DHEA (5 g, 17.36 mmol) and 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (11.8 g, 52.08 mmol) in dioxane
100 mL was refluxed under nitrogen for 24 h according to the
procedures reported by Furst et al. [27].
(b) Super-hydride 10 equiv. (550.8 mg, 5.2 mmol): 2 (37 mg,
23%), 4 (43 mg, 27%), and starting material (49 mg, 25%).
(c) Super-hydride 12 equiv. (660.9 mg, 6.24 mmol): 4 (104 mg,
52%).
2.5.
Reduction of 1,4,6-androstatriene-3,17-dione
2.5.1. Reduction with NaBH4
According to a procedure by Ma et al. [29], to a solution of
compound 7 (200 mg, 0.71 mmol) in absolute ethanol 20 mL
was added NaBH4 (108 mg, 2.84 mmol) at room temperature to
afford 1,4,6-androstatriene-3,17-diol (8). Yield: 169 mg (83%).
2.3.6. Reduction with BH3·(CH3)2S
(a) BH3·(CH3)2S 4 equiv.: To a solution of compound 1 (200 mg,
0.52 mmol) in anhydrous THF 8 mL, was added BH3·(CH3)2S
(158 mg, 2.08 mmol) at room temperature and stirred
under nitrogen for 1 h at same temperature. The reaction
mixture was mixed with H2O and extracted with ethyl
acetate. The extract was dried over anhydrous MgSO4, fil-
tered, and evaporated to obtain crude yellow oils, which
was purified with column chromatography on silica gel
(ethyl acetate/n-hexane = 1:9) to give 5 (43 mg, 22%) and 2
(19 mg, 10%).
2.5.2. Reduction with l-Selectride
To a solution of compound 7 (200 mg, 0.71 mmol) in anhydrous
THF 8 mL was added l-Selectride (1.62 g, 8.52 mmol) at room
temperature for 18 h to afford crude compound. Column chro-
matography on silica gel, eluting with ethyl acetate/n-hexane
(1:5) gave white crystal of 4,6-androstadiene-3␣,17-diol (9).
Yield: 129 mg (63%).
(b) BH3·(CH3)2S 10 equiv. (395 mg, 5.2 mmol): 5 (67 mg, 35%), 2
(31 mg, 16%).
2.5.3. Reduction with LiAlH4
(a) LiAlH4 6 equiv.: To a solution of compound 7 (200 mg,
0.71 mmol) in anhydrous THF 15 mL was added LiAlH4
(162 mg, 4.26 mmol) at room temperature and stirred
under nitrogen at same temperature overnight. The crude
yellow oil obtained was purified with column chromatog-
raphy on silica gel (ethyl acetate/n-hexane = 1:5) to give
3-oxo-1,4,6-androstatrien-17-ol (10, 107 mg, 53%), 3-oxo-
4,6-androstadien-17-ol (11, 32 mg, 16%), and starting
material (22 mg, 11%).
(c) BH3·(CH3)2S 11 equiv. (434.5 mg, 5.72 mmol): 5 (85 mg, 44%).
4,6-Cholestadien-3␣-ol (3): mp: 91–93 ◦C, IR (KBr) cm−1
:
3440, 2935, 2859, 1462, 1374, 1272, 1H NMR (CDCl3) ı: 0.72 (3H, s,
H-18), 0.85 (3H, s, H-26), 0.88 (3H, s, H-27), 0.91 (3H, d, J = 6.4 Hz,
H-21), 0.99 (3H, s, H-19), 4.21–4.39 (1H, m, H-3), 5.35 (1H, s, H-
5), 5.63 (1H, d, J = 10.0 Hz, H-6), 5.90 (1H, dd, J = 2.4 Hz, 10.0 Hz,
H-7), 13C NMR (CDCl3) ı: 145.0, 131.8, 128.0, 126.0, 68.2, 56.2,
54.1, 51.5, 43.5, 39.9, 39.6, 37.5, 36.3, 35.9, 35.2, 33.7, 29.2, 28.4,
28.1, 24.0, 23.9, 23.0, 22.7, 20.8, 18.8, 18.2, 12.1, FABMS: 367.2
(M+H-H2O)+.
(b) LiAlH4 10 equiv. (270.8 mg, 7.1 mmol): 10 (77 mg, 38%), 11
(60 mg, 30%), and three spots.
4,6-Cholestadien-3-one (4): mp: 56–58 ◦C, IR (KBr) cm−1
:
2949, 2871, 1663, 1460, 1375, 1267, 1H NMR (CDCl3) ı: 0.76 (3H, s,
H-18), 0.85 (3H, s, H-26), 0.88 (3H, s, H-27), 0.92 (3H, d, J = 6.7 Hz,
H-21), 1.11 (3H, s, H-19), 5.67 (1H, s, H-4), 6.12 (2H, m, H-6,
H-7), 13C NMR (CDCl3) ı: 199.6, 164.1, 141.7, 127.8, 123.5, 56.1,
53.5, 50.7, 43.5, 39.7, 39.6, 37.8, 36.3, 36.2, 35.9, 34.1, 34.0, 28.3,
28.1, 24.0, 23.9, 23.0, 22.7, 20.8, 18.8, 16.4, 12.0, FABMS: 383.2
(M+H)+.
2.5.4. Reduction with Super-hydride
(a) Super-hydride 12 equiv.: To a solution of compound 7
(200 mg, 0.71 mmol) in anhydrous THF (8 mL) was added
dropwise Super-hydride (902.4 mg, 8.52 mmol) for 4 h at
room temperature. The compound obtained was purified
with column chromatography on silica gel, eluting with
ethyl acetate/n-hexane (1:5) to give 10 (32 mg, 16%), 11
(112 mg, 55%), and starting material (30 mg, 15%).
Cholestane (5): mp: 98–101 ◦C, IR (KBr) cm−1: 2930, 2845, 1
H
NMR (CDCl3) ı: 0.78 (3H, s, H-18), 0.85 (3H, s, H-26), 0.88 (3H, s,
H-27), 0.92 (3H, d, J = 6.7 Hz, H-21), 1.12 (3H, s, H-19), 13C NMR
(CDCl3) ı: 58.1, 56.3, 55.2, 47.2, 42,9, 40.7, 39.5, 39.0, 36.5, 36.2,
35.9, 32.129.5, 29.0, 28.5, 28.0, 27.2, 25.5, 24.3, 22.5, 22.0, 21,3,
18.6,12.9, 12.4, FABMS: 373.2 (M+H)+.
(b) Super-hydride 18 equiv. (1.35 g, 12.78 mmol): 10 (26 mg,
13%), 11 (132 mg, 65%), and two spots.
2.5.5. Reduction with BH3·(CH3)2S
1,4,6-Cholestatrien-3␣-ol (6): mp: 70–73 ◦C, IR (KBr) cm−1
:
3415, 2889, 2786, 1258, 1375, 1294, 1H NMR (CDCl3) ı: 0.78 (3H,
d, J = 5.5 Hz, H-18), 0.86 (3H, s, H-26), 0.89 (3H, s, H-27), 0.93
(3H, d, J = 6.4 Hz, H-21), 1.20 (3H, s, H-19), 4.38 (1H, br s, H-3),
(a) BH3·(CH3)2S
6 equiv.: To a solution of compound 7
(200 mg, 0.71 mmol) in anhydrous THF (8 mL) was added
BH3·(CH3)2S (323.6 mg, 4.26 mmol) at room temperature.