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591
1.22, 1.47 Hz, -CH2-O), 4.62 (1H, m, 3␣-H), 1.21 (3H, s,
19-CH3), 0.87 (3H, s, 18-CH3). 13C NMR (CDCl3, 300
MHz): ␦ 219.2 (17-C), 200 (7-C), 164 (5-C), 154 (O-C-O),
131.5 (ϭ C-), 126.5 (6-C), 118.7 (-CH2 ϭ ), 75.7 (3-C),
68.24 (O-CH2), 50.0 (CH), 45.8 (CH), 44.3 (CH), 47.64
(quaternary-C), 38.33 (quaternary-C), 37.7 (CH2), 35.8
(CH2), 35.4, 30.7 (CH2), 27.2 (CH2), 24.02 (CH2), 20.53
(CH2), 17.3 (19-CH3), 13.7 (18-CH3). LC-MS (API-ES,
positive): m/z 409.1 (MϩNa, 100%), 307.1 (MϩNa, -102
(CH2 ϭ CH-CH2OH, CO2), 80%), 285 (M, -101, 52%), 256
(M, -102, -28 (CO), 15%). LC-UV (DAD): max 234 nm.
27.2 (CH2), 25.7 (CH2), 20.7 (CH2), 17.3 (19-CH3), 11.9
(18-CH3). LC-MS (API-ES, positive): m/z 443.2 (MϩNa,
50%), 345.1 (Mϩ1, -MeOH, -CO2, 10%), 301.1 (Mϩ1,
-120 (2ϫ HCOOCH3, 100%)) 269.1 (Mϩ1, -152 (2ϫ
CH3OH, 2ϫ CO2), 5%). LC-UV (DAD): max 236 nm.
3.1.33. 3-Carbooctyloxyandrost-5-ene-7,17-dione (47)
Prepared from 3-hydroxyandrost-5-ene-7,17-dione (2,
Scheme I) and octylchloroformate in pyridine at 0–5°C.
The product (47, Table 1) was purified by column chroma-
1
tography on silica gel. Yield 65%, m.p. 72–3°C. H NMR
(CDCl3, 300 MHz): ␦ 5.77 (1H, d, J ϭ 1.66 Hz, 6-H), 4.6
(1H, m, 3␣-H), 4.13 (2H, t, J ϭ 6.6 Hz, -CH2-O), 1.23 (3H,
s, 19-CH3), 0.88 (3H, s, 18-CH3). 13C NMR (CDCl3, 300
MHz): ␦ 219.8 (17-C), 200.4 (7-C), 164.3 (5-C), 154.3
(O-C-O), 126.5 (6-C), 75.3 (3-C), 68.1 (OCH2), 49.8 (CH),
45.6 (CH), 44.2 (CH), 47.7 (quaternary-C), 38.3 (quaterna-
ry-C), 37.7 (CH2), 35.7 (CH2), 35.5 (CH2), 31.7 (CH2), 30.6
(CH2), 29.1 (CH2), 29.0 (CH2), 28.5 (CH2), 27.2 (CH2),
25.6 (CH2), 24.1 (CH2), 22.5 (CH2), 20.5 (CH2), 14.0
(CH3), 17.3 (19-CH3), 13.7 (18-CH3). LC-MS (APCI, pos-
itive): m/z 459.2 (Mϩ1, 8%), 285.1 (Mϩ1, -174
(CH3(CH2)6CH2OH, CO2, 100%)).
3.1.30. 3-Carboethoxyandrost-5-ene-7,17-dione (44)
Prepared from 7-oxo-DHEA (2) and ethylchloroformate
in pyridine at 0–5°C. Yield 90%, m.p. 187–8°C. H NMR
1
(CDCl3, 300 MHz): ␦ 5.77 (1H, d, J ϭ 1.65 Hz, 6-H), 4.6
(1H, m, 3␣-H), 4.2 (2H, q, J ϭ 7.2 Hz, -CH2-O), 1.32 (3H,
t, J ϭ 7.2 Hz, CH3), 1.23 (3H, s, 19-CH3), 0.9 (3H, s,
18-CH3). 13C NMR (CDCl3, 300 MHz): ␦ 220.2 (17-C),
200.7 (7-C), 164.4 (5-C), 154.3 (O-C-O), 126.7 (6-C), 75.4
(3-C), 64.1 (O-CH2), 49.9 (CH), 45.7 (CH), 44.3 (CH), 47.8
(quaternary-C), 38.4 (quaternary-C), 37.7 (CH2), 35.8
(CH2), 35.6 (CH2), 30.7 (CH2), 27.2 (CH2), 24.1 (CH2),
20.5 (CH2), 14.4 (Ac-CH3), 14.2 (19-CH3), 13.8 (18-CH3).
LC-MS (API-ES, positive): m/z 397.2 (MϩNa, 100%),
285.2 (Mϩ1, -90 (C2H5OH, CO2), 10%). LC-UV (DAD):
max 238 nm.
3.1.34. 3-Carbo(9-fluorenyl)methoxyandrost-5-ene-7,17-
dione (48)
A mixture of 7-oxo-DHEA (2) (0.3 g, 1 mmol) and
9-fluorenylmethylchloroformate (0.285 g, 1.1 mmol) in
pyridine (4.0 ml) was stirred at room temperature for 1 h.
The product (48, Table 1) was purified by column chroma-
tography on silica gel. Yield 57% (0.3 g), m.p. 98–103°C.
1H NMR (CDCl3, 200 MHz): ␦ 7.77 (2H, d, J ϭ 7.11 Hz,
Ar-H), 7.62 (2H, d, J ϭ 6.83 Hz, Ar-H), 7.37 (4H, m, Ar-H),
5.77 (1H, d, J ϭ 1.46 Hz, 6-H), 4.61 (1H, m, 3-H), 4.43 (2H,
d, J ϭ 6.96 Hz, AB system, OCH2), 4.26 (1H, t, J ϭ 7.08
Hz, AB system, Ar-H), 1.25 (3H, s, 19-CH3), 0.90 (3H, s,
18-CH3); LC-MS (API-ES) m/z: 547 (MϩNa, 100%), 285
(Mϩ1, -240 ((9-fluorenyl)methanol, CO2), 3%). LC-UV
(DAD): max 254, 264, 290 and 300 nm.
3.1.31. 3-Carboiso-butoxyandrost-5-ene-7,17-dione (45)
Prepared from 3-hydroxyandrost-5-en-7,17-dione (2)
and iso-butylchloroformate in pyridine at 0–5°C. Yield
1
78%, m.p. 132–3°C. H NMR (CDCl3, 300 MHz): ␦ 5.77
(1H, d, J ϭ 1.66 Hz, 6-H), 4.6 (1H, m, 3␣-H), 3.92 (2H, d,
J ϭ 6.8 Hz, -CH2-O), 1.24 (3H, s, 19-CH3), 0.96 (6H, d, J ϭ
6.6 Hz, (CH3)2), 0.9 (3H, s, 18-CH3). 13C NMR (CDCl3,
300 MHz): ␦ 220.2 (17-C), 200.7 (7-C), 164.4 (5-C), 154.5
(O-C-O), 126.6 (6-C), 75.5 (3-C), 74.1 (O-CH2), 49.9 (CH),
45.7 (CH), 44.3 (CH), 27.7 (CH), 37.8 (CH2), 35.8 (CH2),
35.6 (CH2), 30.7 (CH2), 27.2 (CH2), 24.1 (CH2), 20.6
(CH2), 18.9 (CH3), 18.9 (CH3), 17.4 (19-CH3), 13.7 (18-
CH3). LC-MS (API-ES, positive): m/z 425.2 (MϩNa,
100%), 301.1 (Mϩ1, -102 (HCOO-iso-butyl), 90%), 285.2
(Mϩ1, -118 (iso-butyl alcohol, CO2), 10%), 269.0 (Mϩ1,
-118, -CH3, 3%). LC-UV (DAD): max 236 nm.
3.1.35. 3-Carbomethoxyandrost-5-ene-7,17-diol (49)
3-Carbomethoxyandrost-5-ene-7,17-dione (42) (0.5 g,
0.0014 mol) was dissolved in a mixture of dichloromethane
(5 ml) and methanol (10 ml). The mixture was stirred at
room temperature and finely powdered sodium borohydride
(0.16 g, 0.004 mol) was added slowly. After 15 min the
reaction mixture was quenched with water and the product
was extracted with dichloromethane. The organic layer was
washed, dried and solvent was removed. The product was
crystallized from acetone-petroleum ether to afford 0.35 g
(70%) of 3-carbomethoxyandrost-5-ene-7,17-diol (49,
Table 1) as a white crystalline solid, m.p. 150–52°C.
3.1.32. 3,17-Dicarbomethoxyandrost-5-en-7-one (46)
Prepared from 3,17-dihydroxyandrost-5-en-7-one and
methyl chloroformate in pyridine at 0–5°C. Yield 81%,
m.p. 167–9°C. 1H NMR (CDCl3, 300 MHz): ␦ 5.73 (1H, d,
J ϭ 1.66 Hz, 6-H), 4.57 (2H, m, 3␣-H, 17␣-H), 3.79 (3H, s,
CH3O), 3.77 (3H, s, CH3O), 1.2 (3H, s, 19-CH3), 0.84 (3H,
s, 18-CH3). 13C NMR (CDCl3, 300 MHz): ␦ 201.0 (7-C),
163. 9 (5-C), 155.7 (O-C-O), 154.9 (O-C-O), 126.6 (6-C),
85.7 (17-C), 75.8 (3-C), 54.7 (OCH3), 54.6 (OCH3), 49.7
(CH), 44.9 (CH), 44.6 (CH), 43.0 (quaternary-C), 38.3 (qua-
ternary-C), 37.7 (CH2), 35.8 (CH2), 35.7 (CH2), 27.4 (CH2),
1
LC-MS and H NMR analysis of the product showed a 8:2
ratio of diastereomeric 7-hydroxy and 7␣-hydroxy com-
pounds. 1H NMR for 7-hydroxy isomer (CDCl3, 200
MHz): ␦ 5.33 (1H, s, 6-H), 4.49 (1H, m, 3␣-H), 3.77 (3H,