Androstanes with Modified Carbon Skeletons
2
1
1
[
α]
D
= +41 (c = 8.3 g/L, in CH
2
Cl
2
). H NMR (CDCl
3
, 500 MHz):
(Na
2
SO
4
), and, after filtration, the solvent was evaporated and the
, hexane/
H), 0.86 (d, J = 6.6 Hz, 3 H), 0.94–1.26 (m, 17 H), 1.31–1.34 (m, MTBE = 1:1 Ǟ 1:5) to yield 12 (458 mg, 1.58 mmol, 91%) in the
H), 1.59–1.81 (m, 13 H), 2.06–2.40 (m, 10 H), 2.61 (t, J = 14.1 Hz, main fraction [R (hexane/MTBE = 1:2) = 0.35] as a colorless solid.
both epimers: δ = 0.58 (s, 3 H), 0.59 (s, 3 H), 0.84 (d, J = 6.6 Hz, residue submitted to column chromatography (SiO
2
3
7
1
(
(
(
4
1
3
3
f
H) ppm. 13C{ H} NMR (CDCl
CH
CH
CH
8.78 (CH
3.81 (CH
0.21 (CH
8.72 (CH), 39.95 (CH), 41.84 (CH), 42.36 (C), 43.03 (CH
CH), 54.86 (CH), 212.95 (CO) ppm. IR (ATR): both epimers: ν˜
2936 (m), 2909 (m), 2867 (m), 2845 (m), 1707 (s), 1468 (w), 1451
1
, 125 MHz): 5β-epimer: δ = 12.01 M.p. 131 °C. [α]
), 26.02 (CH ), 30.21 (CH ), 30.68 (CDCl , 500 MHz): δ = 0.66–0.72 (m, 1 H), 0.81 (s, 3 H), 0.86 (s,
), 37.48 (CH ), 41.39 (CH), 41.41
), 42.22 (C), 43.86 (CH), 45.24 (CH), 46.01 (CH), 48.14 (CH),
20
1
3
D 3
= +11.6 (c = 8.35 g/L, CHCl ). H NMR
3
2
2
), 13.81 (CH
), 30.89 (CH
3
), 24.56 (CH
), 34.14 (CH
2
2
2
3
2
2
2
3 H), 0.91–0.94 (m, 3 H), 1.11–1.17 (m, 1 H), 1.19–1.49 (m, 8 H),
1.58–1.68 (m, 3 H), 1.70–1.78 (m, 3 H), 1.81–1.85 (m, 2 H), 2.25
), (dt, J = 17.3, J = 8.7 Hz, 1 H, 16-H), 2.51 (ddd, J = 17.3, J = 10.1,
), J = 1.7 Hz, 1 H, 16-H), 3.62 (tt, J = 11.1, J = 4.8 Hz, 1 H, 3-H),
2
), 54.80 (CH), 211.83 (CO); 5α-epimer: δ = 12.06 (CH
), 24.56 (CH ), 25.70 (CH ), 25.76 (CH ), 27.85 (CH
), 30.76 (CH ), 36.50 (CH ), 37.56 (CH
3
3
2
2
2
2
1
3
1
2
2
2
2
), 38.51 (CH),
), 45.30 (CDCl
24.05 (CH
35.39 (CH), 35.51 (C), 35.65 (CH
4.64 (s, 1 H, 20-H), 4.65 (s, 1 H, 20-H) ppm. C{ H} NMR
2
3
, 125 MHz): δ = 12.25 (CH ), 21.07 (CH
), 28.59 (CH ), 29.30 (CH ), 31.84 (CH
2
), 36.98 (CH ), 38.06 (CH
3
), 18.44 (CH
3
2
),
2
),
2
),
(
=
2
2
2
), 31.36 (CH
2
2
(
1
w), 1373 (w), 1314 (w), 1266 (w), 1244 (w), 1232 (w), 1176 (w), 44.01 (C), 44.86 (CH), 54.37 (CH), 54.53 (CH), 71.01 (CH), 100.57
–
1
102 (w), 1065 (w), 976 (w), 960 (w), 859 (w), 750 (w) cm . GC–
2
(C), 161.72 (CH ) ppm. IR (ATR): ν˜ = 3327 (s, br), 3062 (w), 2925
+
MS (EI, 70 eV): 5β-epimer: m/z (%) = 274 (22) [M ], 232 (18), 218 (vs), 2846 (s), 1653 (m), 1467 (m), 1447 (m), 1368 (m), 1141 (m),
–
1
(
(
(
(
100), 217 (94), 203 (27), 199 (19), 175 (30), 162 (64), 147 (26), 135
19), 107(38); 5α-epimer: m/z (%) = 274 (33) [M ], 232 (17), 218 (12) [M ], 273 (49), 255 (48), 232 (18), 231 (13), 214 (5), 199 (7),
100), 217 (84), 203 (35), 199 (57), 175 (27), 162 (47), 147 (49), 120 189 (7), 188 (13), 176 (5), 173 (5), 163 (48), 162 (68), 149 (14), 147
1077 (m), 1036 (vs), 873 (vs) cm . MS (EI, 70 eV): m/z (%) = 288
+
+
+
30), 107 (55). HRMS (EI): calcd. for C19
H
30O [M] 274.2297; (38), 135 (16), 133 (27), 121 (27), 120 (26), 119 (30), 108 (74), 107
found 274.2290.
(100), 105 (59), 95 (44), 93 (88), 91 (93). HRMS (EI): calcd. for
20
C H
32O [M]+ 288.2453; found 288.2445.
17β-Methylestrane (1):
A
suspension of ketone 10 (80 mg,
0
.29 mmol, 5α/5β = 1.8:1), H NNH ·H O (43.5 mg, 0.87 mmol)
2 2 2
3
1
β-Hydroxy-17β-methyl-5α-androstane (14): A suspension of olefin
2 (458 mg, 1.58 mmol) and Pd/C (50 mg, 10% w/w Pd) in iPrOH
and KOH (31 mg, 0.87 mmol) in DEG (3 mL) and toluene
0.5 mL) was heated under reflux for 1 h. Toluene and H O were
(
2
(
2
11 mL) was hydrogenated with H (3 bar) at 65 °C for 16 h. The
removed by distillation, and the residue was subsequently heated
to 200 °C for 2 h. After cooling to 23 °C, the solution was neutral-
ized with hydrochloric acid (1 mL, 1 mol/ L), diluted with H O
2
mixture was filtered through SiO
=
2
(5 cm, hexane/MTBE = 1:2, R
f
0.41), and the solvent was evaporated to yield 14 (446 mg,
2
0
1.53 mmol, 97%) as a colorless solid. M.p. 127 °C. [α]
D
= +6.5 (c
(5 mL) and extracted with MTBE (3ϫ20 mL). The combined or-
1
=
10.4 g/L, CHCl
H), 0.64–0.69 (m, 1 H), 0.84 (s, 3 H), 0.85 (d, J = 6.8 Hz, 3 H, 17-
CH ), 0.88–1.03 (m, 4 H), 1.02–1.84 (m, 19 H), 3.61 (tt, J = 11.1,
J = 4.8 Hz, 1 H, 3-H) ppm. C{ H} NMR (CDCl
11.97 (CH ), 12.29 (CH ), 13.75 (CH ), 20.97 (CH
CH ), 28.71 (CH ), 30.11 (CH ), 31.41 (CH ), 32.17 (CH
C), 35.67 (CH), 37.06 (CH ), 37.53 (CH ), 38.13 (CH ), 42.00 (C),
4.96 (CH), 45.03 (CH), 54.73 (CH), 55.76 (CH), 71.10 (CH) ppm.
IR (ATR): ν˜ = 3299 (br. s), 2931 (vs), 2865 (s), 2846 (s), 1469 (m),
447 (m), 1369 (m), 1343 (m), 1133 (m), 1083 (m), 1039 (vs), 731
3 3
). H NMR (CDCl , 500 MHz): δ = 0.56 (s, 3
4
ganic layers were dried (MgSO ), filtered and the solvents evapo-
rated. The crude product was purified by column chromatography
3
(SiO
2
, hexane/MTBE = 2:1, R
f
= 0.73) to give two epimers (ratio
1
3
1
3
, 125 MHz): δ
), 24.65
), 35.51
5
7
α/5β = 1.8:1 by GLC) of the title compound 1 (60 mg, 0.23 mmol,
=
(
(
3
3
3
2
9%) as a colorless oil. [α]2
1
= +20 (c = 8.2 g/L, in CH
Cl
). H
1
D
2
2
2
2
2
2
2
NMR (500 MHz, CDCl
J = 6.9 Hz, 3 H), 0.77 (d, J = 6.9 Hz, 3 H), 0.81–1.74 (m, 50 H),
3
): both epimers: δ = 0.48 (s, 6 H), 0.76 (d,
2
2
2
4
.81–1.84 (m, 2 H) ppm. 13C{ H} NMR (125 MHz, CDCl
epimer: δ = 13.84 (CH ), 12.03 (CH ), 24.57 (CH ), 25.55 (CH
), 30.23 (CH ), 30.39 (CH ), 31.32 (CH
), 34.63 (CH ), 37.67 (CH
3.39 (CH), 45.27 (CH), 47.59 (CH), 48.87 (CH), 55.16 (CH); 5α-
1
1
3
): 5β-
3
3
2
2
),
),
1
2
3
4
6.51 (CH
2
), 26.93 (CH
2
2
2
2
–
1
+
(
(
(
s) cm . MS (EI, 70 eV): m/z (%) = 290 (29) [M ], 275 (34), 257
32), 248 (14), 234 (78), 233 (65), 215 (29), 216 (42), 215 (84), 165
57). HRMS (EI): calcd. for C20
4.18 (CH
2
2
2
), 41.71 (CH), 42.19 (C),
+
H34O for C20
H
34O [M] 290.2610;
epimer: δ = 13.84 (CH
3
), 12.39 (CH
), 26.97 (CH
), 37.45 (CH), 37.75 (CH
1.50 (CH), 42.32 (C), 42.36 (CH), 45.35 (CH), 55.03 (CH) ppm.
3
), 20.39 (CH
2
), 24.65 (CH
2
),
found 290.2604.
2
3
4
5.62 (CH
2
), 26.61 (CH
), 32.52 (CH
2
2
), 27.01 (CH
2
), 28.64 (CH
2
), 38.96 (CH),
2
),
0.29 (CH
2
2
1
7β-Methyl-5α-androstan-3-one (13): PCC (851 mg, 3.95 mmol) was
added to a solution of alcohol 14 (446 mg, 1.53 mmol) in CH Cl
40 mL). The resulting mixture was stirred at 23 °C for 2 h and
2
2
IR (ATR): both epimers: ν˜ = 2912 (s), 2864 (m), 1446 (m), 1378
(
–1
(m), 1334 (w), 1257 (w), 1098 (w), 1057 (w), 970 (w) cm . GC–MS
(EI, 70 eV): 5β-epimer: m/z (%) = 260 (21), 245 (6), 218 (19), 204
(83), 203 (100), 189 (26), 148 (24), 135 (20), 121 (14), 67 (17); 5α-
2
then diluted with MTBE (40 mL). Filtration through SiO (5 cm,
hexane/MTBE = 1:2, R
yielded 13 (415 mg, 1.44 mmol, 94%) as a colorless solid. M.p.
f
= 0.57) and evaporation of the solvent
epimer: m/z (%) = 260 (20), 245 (5), 218 (16), 204 (83), 203 (100),
89 (24), 148 (22), 135 (218), 121 (16), 67 (17). HRMS (EI): calcd.
20
1
137 °C. [α]
500 MHz): δ = 0.47 (s, 3 H), 0.64–0.71 (m, 1 H), 0.74 (d, J = 6.8 Hz,
3 H, 17-CH ), 0.79–0.90 (m, 3 H), 0.93 (s, 3 H), 0.99–1.72 (m, 14
D 3 3
= +29 (c = 9.4 g/L, CHCl ). H NMR (CDCl ,
1
+
for C19
β-Hydroxy-17-methylene-5α-androstane (12): A suspension of
Ph PMe]Br (939 mg, 2.63 mmol) and NaH (350 mg of a 60% dis-
persion in mineral oil, 8.76 mmol) in abs. THF (20 mL) under an
inert gas was stirred at 70 °C for 15 min. A solution of 11 (509 mg, 125 MHz): δ = 11.20 (CH
.75 mmol) in abs. THF (10 mL) was added dropwise, and the re- (CH ), 24.46 (CH ), 28.75 (CH
(CH), 35.49 (C), 37.22 (CH ), 37.83 (CH
44.40 (CH ), 44.80 (CH), 46.55 (CH), 53.97 (CH), 55.34 (CH),
H32 [M] 260.2504; found 260.2499.
3
3
[
H), 2.01 (dt, J = 15.0, J = 2.9 Hz, 1 H), 1.95 (ddd, J = 13.1, J =
6.5, J = 2.0 Hz, 1 H), 2.18 (d, J = 14.3 Hz, 1 H), 2.20–2.24 (m, 1 H),
2.31 (dt, J = 6.6, J = 14.3 Hz, 1 H) ppm. C{ H} NMR (CDCl
), 11.78 (CH ), 13.56 (CH ), 20.98
), 29.89 (CH ), 31.61 (CH ), 35.35
), 38.39 (CH ), 41.80 (C),
3
1
3
1
3
,
3
3
3
1
2
2
2
2
2
sulting mixture was further stirred at 70 °C for 16 h. After cooling
to ambient temperature, some water was added dropwise, and then
the mixture was diluted with water (75 mL) and MTBE (75 mL).
The layers were separated, and the aqueous layer was extracted
with MTBE (2ϫ50 mL). The combined organic layers were dried
2
2
2
2
211.07 (C) ppm. IR (ATR): ν˜ = 2930 (s), 2865 (s), 2843 (m), 1712
(vs), 1442 (m), 1431 (m), 1367 (m), 1228 (m), 965 (m), 879 (m), 683
(m) cm . MS (EI, 70 eV): m/z (%) = 288 (84) [M ], 273 (24), 255
–
1
+
Eur. J. Org. Chem. 2011, 4543–4550
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4547