M. Numazawa et al. / Steroids 68 (2003) 503–513
505
1
4 (3.8 g, 9.45 mmol) in THF (26 ml) was added dropwise
of 2- and 2␣-methyl compounds 5 and 6. This mixture
was purified by column chromatography (hexane–EtOAc,
4:1 v/v) and subsequent high-performance liquid chro-
matography (HPLC), giving the 2-methyl compounds
as the analytical samples. HPLC conditions: pump, Wa-
ters M510 (Waters, Milford, MA, USA); mobile phase,
CH3CN–H2O (45:15 v/v, 4 ml/min); stationary phase, C18
column (5 m, 250 mm × 10 mm, Mightysil, Kanto Chem-
ical Co. Inc., Tokyo, Japan); detector, Waters UV detec-
tor 486 (at 250 nm). 2-Methyl steroid 5 (retention time:
to this suspension, and the reaction mixture was heated for
4
to afford a solid that was suspended in THF (28 ml). Fil-
tration and evaporation provided a crude product, which
was purified by column chromatography (hexane–EtOAc,
◦
5 h at 80 C. After this time, the solvent was evaporated
15:1 v/v) to yield 2-methylene compound 15 (275 mg, 7%)
along with the recovered starting material 14 (1.53 g, 41%).
◦
1
Compound 15: m.p. 158–160 C (from acetone). H NMR
δ: 0.010 and 0.016 [3H each, s, 17-Si(Me)2], 0.75 (3H,
s, 18-Me), 0.88 (9H, s, 17-Si(Me)2C(Me)3), 1.11 (3H, s,
◦
36.4 min): m.p. 168–170 C. 2␣-Methyl steroid 6 (retention
◦
1
9-Me), 3.56 (1H, t, J = 8.2 Hz, 17␣-H), 5.22 and 5.83
time: 39.0 min): m.p. 149–152 C. The two compounds
(
1H each, s, 2-C=CH2), 5.94 (1H, t, J = 2.1 Hz, 4-H).
were identical to the corresponding samples synthesized
above.
−
1
FT-IR (KBr): 1666 (C=O) and 1624 (C=C) cm . UV λmax:
+
2
5
61 nm (ε = 16,400). MS m/z (relative intensity): 414 (M ,
), 357 (99), 281 (20), 75 (100). Analysis calculated for
2.10. Reaction of 17β-(tert-butyldimethylsiloxy)-6,19-
C H42O2Si: C, 75.30; H, 10.21. Found: C, 75.15; H, 10.41.
2
6
epoxyandrost-4-en-3-one (18) with methyliodide-tert-BuOK
2
.7. 2-Methylene-17β-hydroxyandrost-4-en-3-one (16)
A solution of compound 18 (4.4 g, 10.6 mmol) and MeI
(
12 ml) in THF (45 ml) was added to a suspension of
A solution of 17-siloxy steroid 15 (260 mg, 0.62 mmol)
◦
tert-BuOK (2.05 g, 18.2 mol) in 140 ml of THF at −60 C,
while stirring under a stream of N2 gas, and the mixture was
stirred for 45 min. After this time, the mixture was diluted
with EtOAc (1000 ml), washed with 5% HCl, 5% NaHCO3
solution, and water, sequentially, and dried with Na2SO4.
Evaporation of the solvent gave an oily product that was pu-
rified by silica gel column chromatography (hexane–EtOAc,
in THF (6 ml) and propan-2-ol (6 ml) was treated with 1 M
HCl (3.5 ml) overnight at room temperature, and the result-
ing mixture was neutralized by adding NaHCO3, diluted
with EtOAc (200 ml), washed with water, and dried with
Na2SO4. Evaporation of the solvent gave a solid that was re-
crystallized from acetone to yield 17-ol 16 (170 mg, 92%).
◦
1
M.p. 149–151 C. H NMR δ: 0.80 (3H, s, 18-Me), 1.07
3H, s, 19-Me), 3.66 (1H, t, J = 8.4 Hz, 17␣-H), 5.22
1
2
5:1 v/v) to yield the 2,2-dimethyl product 19 (880 mg,
0%) and the 2␣-methyl product 20 (720 mg, 17%) along
(
and 5.84 (1H each, s, 2-C=CH2), 5.94 (1H, t, J = 2.1 Hz,
−
1
with the recovered starting material 18 (2.5 g, 61%).
4
2
2
-H). FT-IR: 1668 (C=O) and 1620 (C=C) cm . UV λmax:
+
59 nm (ε = 11,100). MS m/z (relative intensity): 300 (M ,
6), 147 (13), 134 (63), 41 (100). Analysis calculated for
2
.11. 2,2-Dimethyl-17β-(tert-butyldimethylsiloxy)-6,19-
C20H28O2: C, 79.95; H, 9.39. Found: C, 79.68; H, 9.50.
epoxyandrost-4-en-3-one (19)
2
.8. 2-Methyleneandrost-4-ene-3,17-dione (17)
◦
1
M.p. 73–76 C (from EtOAc). H NMR δ: 0.002 and 0.008
3H each, s, 17-OSi(Me)2C(Me)3], 0.80 (3H, s, 18-Me),
0
[
1
7-Hydroxy steroid 16 (70 mg, 0.23 mmol) in acetone
.88 [9H, s, 17-OSi(Me)2C(Me)3], 1.15 and 1.22 (3H each,
◦
(24 ml) was treated with Jones reagent for 3 min at 0 C as
s, 2-Me and 2␣-Me), 3.46 and 4.20 (1H each, d, J = 8 Hz,
described above. A crude product was obtained and recrys-
tallized from acetone to give 17-ketone 17 (60 mg, 90%).
M.p. 194–197 C. H NMR δ: 0.92 (3H, s, 18-Me), 1.13
1
5
9-CH2), 3.56 (1H, t, J = 8 Hz, 17␣-H), 4.66 (1H, d, J =
1
−
Hz, 6␣-H), 5.80 (1H, s, 4-H). FT-IR: 1675 (C=O) cm
.
◦
1
+
MS m/z (relative intensity): 447 (M , 27), 403 (13), 387
100), 357 (23). Analysis calculated for C27H44O3Si: C,
2.91; H, 9.97. Found: C, 73.16; H, 9.77.
(
3H, s, 19-Me), 5.24 and 5.86 (1H each, s, 2-C=CH2), 5.94
(
7
(
1
1H, t, J = 2.1 Hz, 4-H). FT-IR: 1738 and 1672 (C=O) and
−
1
621 (C=C) cm . UV λmax: 259 nm (ε = 13,200). MS m/z
+
(relative intensity): 298 (M , 82), 147 (19), 134 (100). Anal-
ysis calculated for C20H O2: C, 80.49; H, 10.78. Found:
C, 80.88; H, 10.91.
2.12. 2α-Methyl-17β-(tert-butyldimethylsiloxy)-6,19-
epoxyandrost-4-en-3-one (20)
26
◦
1
2
.9. Hydrogenation of 2-methylene steroid 17 with
M.p. 118–120 C (from MeOH). H NMR δ: 0.004 [6H,
s, 17-OSi(Me) C(Me) ], 0.80 (3H, s, 18-Me), 0.875 [9H,
H2-tris(triphenylphosphine)rhodium chloride
2
3
s, 17-OSi(Me)2C(Me)3], 1.20 (3H, d, J = 7.3 Hz, 2␣-Me),
A solution of 2-methylene compound 17 (180 mg,
.60 mmol) in THF and toluene (1:1) (20 ml) was hydro-
genated with the rhodium complex (200 mg, 0.22 mmol)
for 17 h, filtered, and evaporated to provide a 1:1 mixture
3.55 (2H, m, 19-Ha and 17␣-H), 4.13 (1H, d, J = 7.8 Hz,
0
19-H ), 4.61 (1H, d, J = 5.3 Hz, 6␣-H), 5.85 (1H, s, 4-H).
b
−
1
FT-IR: 1663 (C=O) cm . UV λmax: 239 nm (ε = 11,900).
+
MS m/z (relative intensity): 430 (M , 3), 373 (100), 343 (4),