give 5 (3.7 g, 74%).
Reduction of 3 ,5-Cyclo-5 -androstan-6,17-dione (5). A cooled (0oC) solution of 5 (0.10 g) in methanol (7 mL) was
treated with NaBH (0.013 g), stirred at 0oC for 0.5 h, and treated with acetic acid (0.5 mL). The solvent was removed under
4
vacuum. The solid was dissolved in THF (3 mL). The solution was filtered through a layer of aluminum oxide. The filtrate
1
was evaporated to dryness under vacuum. Yield of 6 and 7 (4:3 ratio according to H NMR), 0.118 g. IR spectrum (film,
, cm-1): 1750 (C17 O), 1695 (C O). H NMR spectrum ( , ppm): 6: 0.76 (3H, s, 18-Me), 0.94 (3H, s, 19-Me), 3.68 (1H, m,
1
6
W/2 = 27 Hz, H-17 ); 7: 0.81 (3H, s, 18-Me), 1.07 (3H, s, 19-Me), 3.92 (1H, m, W/2 = 19 Hz, H-6 ).
3 ,5-Cyclo-B-homo-6-oxa-5 -androstan-6 ,17-dione (8). A solution of 5 (0.30 g) in CH Cl (10 mL) was treated
2
2
with a solution of trifluoroacetic acid (prepared by dissolving 1.0 mL trifluoroacetic anhydride in 15 mL CH Cl with subsequent
2
2
dilution with 0.3 mL of 30% H O ). The mixture was stirred at room temperature for 0.5 h and filtered through a layer of
2
2
aluminum oxide. The filtrate was evaporated under vacuum at room temperature. The solid was chromatographed on a silica-
gel column with elution by ether:hexane (1:1). Yield of 8, 0.10 g (32%), mp 196-199 C (hexane—acetone). Found (%): C
75.20, H 8.74. Calc. for C19H26O3 (%): C 75.43, H 8.66. IR spectrum (KBr, , cm-1): 1740 (C O). H NMR spectrum ( , ppm):
1
0.92 (3H, s, 18-Me), 1.08 (3H, s, 19-Me).
3 -Bromo-5 -androstan-6,17-dione (9). A solution of 5 (1.0 g) in glacial acetic acid (10 mL) was treated dropwise
with HBr (1.5 mL), stirred at 13oC for 15 min, and diluted with water (15 mL). The product was extracted with CH Cl . The
2
2
organic layer was washed successively with water, saturated NaHCO solution, and water, was filtered through a layer of
3
aluminum oxide, and was evaporated under vacuum to dryness. Yield of 9, 1.17 g (91%), mp 187-189 C (hexane—acetone),
lit. [13] mp 184oC.
IR spectrum (KBr, , cm-1): 1750 (C17 O), 1725 (C O). H NMR ( , ppm): 0.84 (3H, s, 19-Me), 0.88 (3H, s, 18-Me),
1
6
3.96 (1H, m, W/2 = 26 Hz, H-3 ).
5 -Androst-2-en-6,17-dione (10). A. A solution of 9 (0.90 g) in DMF (3 mL) was treated with Li CO (0.90 g) and
2
3
LiBr (0.30 g), boiled for 0.5 h, cooled to room temperature, diluted with water, and extracted with benzene. The benzene extract
was washed with water and evaporated under vacuum. The solid was chromatographed on a silica-gel column with elution by
benzene:hexane (3:1).
Yield of 10 in fraction 1: 0.16 g (23%). IR spectrum (KBr, , cm-1): 1750 (C17 O), 1720 (C O), 1670 (C C).
H
1
6
NMR spectrum ( , ppm): 0.74 (3H, s, 19-Me), 0.89 (3H, s, 18-Me), 5.60 and 5.69 (1H, m, W/2 = 11 Hz, H-2 and H-3); of 10
and 5 in fraction 2, 0.35 g (50%); of 5 in fraction 3, 0.21 g (30%).
B. A solution of 5 (78.8 mg) in sulfolane (4 mL) was treated with p-toluenesulfonic acid (6 mg), heated at ~170oC for
3 h, cooled to room temperature, diluted with water (10 mL), and extracted with hexane. The extract was washed with water,
filtered through a layer of aluminum oxide, and evaporated under vacuum to dryness. Yield of 10, 63 mg (81%).
Woodward cis-Hydroxylation of 10. A stirred solution of 10 (0.512 g) in acetic acid (20 mL) and water (1 mL) at
43oC was treated successively with silver acetate (0.9 g) and iodine (0.5 g). The temperature of the reaction mixture was
adjusted to 55-60oC. Stirring was continued for 2 h. The reaction mixture was cooled to room temperature and filtered through
a layer of aluminum oxide. The filtrate was diluted with water (20 mL). The product was extracted with dichloroethane. The
organic layer was washed with water. The solvent was removed under vacuum. The solid was treated with methanol (10 mL),
water (0.5 mL), and K CO (0.2 g). The mixture was refluxed for 1 h, cooled to room temperature, and filtered through a layer
2
3
of aluminum oxide. The filtrate was diluted with water (25 mL) and extracted with dichloroethane. The extract was washed
with water. The solvent was removed completely under vacuum. The solid was dissolved in pyridine (3 mL), added to acetic
acid solution (2 mL), held at room temperature for 20 h, diluted with water, and extracted with dichloroethane. The extract was
washed with water. The solvent was removed under vacuum. The solid was separated on a silica-gel column with elution by
dichloroethane:THF (1:1).
1
1
Yield of 11a and 12 in fraction 1, 183 mg (25%) (according to H NMR). H NMR spectrum ( , ppm): 11a: 0.88 (3H,
s, 18-Me), 0.98 (3H, s, 19-Me), 2.02 (3H, s, AcO), 2.09 (3H, s, AcO), 4.82 (1H, m, W/2 = 22 Hz, H-3 ), 5.32 (1H, m,
W/2 = 10 Hz, H-2 ); 12: 0.88 (3H, s, 18-Me), 1.06 (3H, s, 19-Me), 2.02 (3H, s, AcO), 2.13 (3H, s, AcO), 4.95 (1H, m,
W/2 = 22 Hz, H-2 ), 5.38 (1H, m, W/2 = 10 Hz, H-3 ); of 11b in fraction 2, 52 mg (8%), mp 224-227oC (methanol). IR
spectrum (KBr, , cm-1): 1740 (AcO, C17 O), 1715 (C O). H NMR spectrum ( , ppm): 0.89 (3H, s, 18-Me), 1.05 (3H, s,
1
6
19-Me), 2.11 (3H, s, AcO), 3.51 (1H, d, J = 5 Hz, H-4 ), 4.12 (1H, m, W/2 = 9 Hz, H-2 ), 4.77 (1H, m, W/2 = 22 Hz, H-3 ).
Acetylation of 11b. A solution of 11b (43 mg) in pyridine (3 mL) was treated with acetic anhydride (1 mL) and 4-
dimethylaminopyridine (5 mg), held for 4 d at room temperature, diluted with water, and extracted with dichloroethane. The
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