M.V. Dansey et al. / Steroids 121 (2017) 40–46
43
stirring continued at room temperature for 2 h. The reaction mix-
ture was diluted with ether and percolated through silicagel with
ether-ethyl acetate (1:1) to give the corresponding 3-ketosteroid
(39.1 mg, 80%) as an amorphous solid; 1H NMR (200.13 MHz):
5.35(1H, bs, H-6), 3.67 (3H, m, 25-COOCH3), 3.30 (1H, d,
J = 17 Hz, H-4a), 2.83 (1H, d, J = 17 Hz, H-4b), 1.19 (3H, s, H-19),
0.65 (3H, s, H-18).
(75 mg, 0.23 mmol) in anhydrous DMF (1.8 ml) and the solution
was stirred for 4 h at room temperature under nitrogen atmo-
sphere. The reaction mixture was extracted with ether. The organic
layer was washed successively with brine and water and dried
with sodium sulphate. Evaporation of the solvent followed by flash
chromatography (ethyl acetate–hexane 30:70) gave the 3-silyl
ether 19 (93 mg, 92%) as an amorphous solid; IR (KBr) tmax
:
To a solution of the solid obtained above in THF (1 ml), HCl 6 N
2933, 2853, 1707, 1076, 1007 cmÀ1 1H NMR (500.13 MHz, CDCl3)
;
(170
l
L) was added. The reaction mixture was stirred 24 h at room
d: 5.37 (1H, d, J = 1.8, H-4), 4.41 (1H, d, J = 4.8, H-6), 4.36 (1H, m, H-
3), 4.02 (1H, d, J = 7.7, H-19), 3.28 (1H, d, J = 7.7, H-19), 2.51 (1H, t,
J = 9.0, H-17), 2.17 (1H, m, H-16b), 2.11 (3H, s, H-21), 2.04 (1H, m,
temperature, diluted with water, concentrated to a third of its vol-
ume, and extracted with ethyl acetate. The organic layer was dried
with sodium sulphate and the solvent evaporated under vacuum.
The resulting solid was purified by preparative TLC (ethyl acet-
ate-hexane 20:80) to give compound 7 as an amporphous solid
(20.7 mg, 55%) and the 3-ketosteroid used as starting material
(15.6 mg, 40%). Compound 7: [
(KBr) max: 3401, 2938, 1720, 1705, 1458, 1386, 1259, 1051,
1022 cmÀ1 1H NMR (500.13 MHz): 5.74 (1H, s, H-4), 2.51 (1H, t,
H-12b), 1.97 (1H, m, H-1
(1H, m, H-2b), 1.79 (1H, m, H-8), 1.64 (2H, m, H-11
1.60 (1H, m, H-15b), 1.59 (1H, m, H-9), 1.58 (1H, m, H-2
(1H, m, H-12 ), 1.32 (1H, m, H-14), 1.31 (1H, m, H-1b), 1.29 (1H,
m, H-11b), 1.26 (1H, m, H-15 ), 1.25 (1H, m, H-7 ), 0.91 (9H, s,
a
), 1.89 (1H, dt, J = 12.8 and 5.0 H-7b), 1.80
and H-16 ),
), 1.45
a
a
a
a
a]
20 = +20.9 (c = 0.2, methanol); IR
a
a
D
t
(CH3)3CSi), 0.67 (3H, s, H-18), 0.10 (3H, s, (CH3)2Si), 0.09 (3H, s,
(CH3)2Si); 13C NMR (125.77 MHz, CDCl3) d: 209.4 (C-20), 147.8
(C-5), 117.0 (C-4), 77.1 (C-6), 75.5 (C-19), 68.5 (C-3), 63.5 (C-17),
55.1 (C-14), 49.5 (C-9), 44.8 (C-10), 44.3 (C-13), 39.2 (C-7), 38.8
(C-12), 34.4 (C-8), 31.4 (C-21), 29.2 (C-2), 26.0 ((CH3)3CSi), 25.4
(C-1), 23.9 (C-15), 22.9 (C-16), 22.9 (C-11), 18.4 ((CH3)3CSi), 13.7
(C-18), -4.48 ((CH3)2Si), -4.55 ((CH3)2Si); Analysis C27H44O3Si: calcd
C, 72.9, H, 10.0 Found C, 72.4, H, 10.1.
;
J = 9.0 Hz, H-17), 2.42 (1H, m, H-24a), 2.40 (1H, m, H-6b), 2.39
(2H, m, H-21), 2.37 (3H, m, H-24b and H-2), 2.29 (1H, ddd,
J = 2.5, 4.0 and 14.5 Hz, H-6
H-1b), 2.03 (1H, m, H-12b), 1.87 (1H, m, H-7b), 1.71 (2H, m, H-
and H-15 ), 1.67 (1H, m, H-16b), 1.63 (4H, m, H-22 y H-23),
1.62 (1H, m H-11 ), 1.56 (1H, m, H-8), 1.44 (1H, m, H-11b), 1.43
(1H, m, H-12 ), 1.27 (1H, m, H-15b), 1.16 (1H, m, H-14), 1.19
(3H, s H-19), 1.06 (1H, td, J = 12.9 and 4.2, H-7 ), 0.98 (1H, m, H-
a),2.19 (1H, m, H-16a), 2.04 (1H, m,
1a
a
a
a
a
2.2.7. 7-(3a-t-Butyldimethylsilyloxy-6,19-epoxyandrost-4-ene-17b-
9), 0.65 (3H, s, H-18); 13C NMR (125.77 MHz): 210.8 (C-20),
199.5 (C-3), 177.3 (C-25), 171.0 (C-5), 123.9 (C-4), 62.7 (C-17),
56.1 (C-14), 53.65 (C-9), 44.1 (C-13), 43.8 (C-21), 38.8 (C-10),
38.6 (C-12), 35.7 (C-1), 35.6 (C-8), 33.9 (C-24), 33.5 (C-2), 32.8
(C-6), 31.9 (C-7), 24.4 (C-22), 24.3 (C-15), 23.00 (C-16), 22.99 (C-
23), 21.0 (C-11), 17.4 (C-19), 13.5 (C-18); HR MS-ESI: calculated
for C25H37O4 401.2686, found 401.2697.
il)-7-oxo-5-hydroxymethylheptanoate (22)
The silyl enol ether 20 was obtained from compound 19
(102 mg, 0.23 mmol) following the procedure described for com-
pound 12. Compound 20: 1H NMR (500.13 MHz, CDCl3) d: 5.35
(1H, bs, H-4), 4.40 (1H, d, J = 4.5, H-6), 4.35 (1H, m, H-3), 4.08
(1H, d, J = 1.0, H-21a), 4.03 (1H, d, J = 1.0, H-21b), 4.03 (1H, d,
J = 7.5, H-19a), 3.27 (1H, d, J = 7.5, H-19b), 2.00 (1H, t, J = 9.5, H-
17), 1.99 (1H, m, H-16b), 1.98 (1H, m, H-1
12b), 1.86 (1H, m, H-7b), 1.79 (1H, m, H-2b), 1.76 (1H, m, H-8),
1.68 (1H, m, H-16 ), 1.61 (1H, m, H-12 ), 1.56 (2H, m, H-2 and
H-15b), 1.55 (2H, m, H-11 and H-9), 1.28 (1H, m, H-1b), 1.25
(1H, m, H-11b), 1.22 (1H, m, H-7 ), 1.20 (2H, m, H-4 and H-15 ),
0.90 (9H, s, ((CH3)3CSi)), 0.66 (3H, s, H-18), 0.19 (9H, s, ((CH3)3Si)),
0.09 (3H, s, ((CH3)2Si)), 0.08 (3H, s, ((CH3)2Si)); 13C NMR
(125.77 MHz, CDCl3) d: 160.0 (C-20), 148.0 (C-5), 116.8 (C-4),
89.7 (C-21), 77.2 (C-6), 75.6 (C-19), 68.7 (C-3), 56.1 (C-17), 54.3
(C-14), 49.8 (C-9), 44.4 (C-10), 43.9 (C-13), 39.3 (C-7), 38.5 (C-
12), 34.7 (C-8), 29.2 (C-2), 25.9 ((CH3)3CSi), 25.4 (C-1), 24.6 (C-
16), 23.7 (C-15), 23.0 (C-11), 18.4 ((CH3)3CSi), 13.1 (C-18), 0.15
((CH3)3Si), -4.5 ((CH3)2Si), -4.6 ((CH3)2Si).
a), 1.97 (1H, m, H-
2.2.5. 6-(3b-Hydroxy-5-androstene-17b-il)-6-oxo-hexanoic acid (8)
To a solution of compound 17 (24 mg, 0.058 mmol) in methanol
(0.6 ml) and THF (0.6 ml), 5% aqueous LiOH (0.12 ml, 0.6 mmol)
was added. The reaction mixture was stirred for 18 hs at room
temperature, diluted with water and concentrated to a third of
its volume. After addition of HCl 1 N (pH 3) the mixture was
extracted with ethyl acetate. The organic layer was washed with
water, dried with sodium sulphate and the solvent evaporated
under vacuum. The resulting solid was purified by preparative
TLC (ethyl acetate – hexane 7:3) to give compound 8 (22 mg,
a
a
a
a
a
a
92%) as an amorphous solid; [
(KBr) tmax 3396, 2937, 2164, 1718, 1698, 1463, 1226,
1049 cmÀ1 1H NMR (500.13 MHz): 5.35 (1H, bs, H-6), 3.52 (1H,
m, H-3), 2.51 (1H, t, J = 9.0 Hz, H-17), 2.40 (2H, t, J = 2.4 Hz, H-
21), 2.32 (2H, m, H-24), 2.30 (1H, m, H-4 ), 2.23 (1H, m, H-4b),
2.18 (1H, m, H-16 ), 2.00 (2H, m, H-12b and H-7b), 1.85 (2H, m,
H-1b and H-2 ), 1.69 (1H, m, H-15 ), 1.65 (1H, m, H-16b), 1.62
(1H, m, H-11 ), 1.60 (4H, m, H-22 and H-23), 1.59 (1H, m, H-7 ),
1.52 (1H, m, H-2b), 1.48 (1H, m, H-8), 1.47 (1H, m, H-11b), 1.43
(1H, m, H-12 ), 1.23 (1H, m, H-15b), 1.14 (1H, m, H-14), 1.09
(1H, m, H-1 ), 1.01 (3H, s H-19), 0.99 (1H, m, H-9), 0.61 (3H, s,
a]
20 = +18.2 (c = 0.4, methanol); IR
D
:
;
Compound 22 was obtained from the silyl eno ether 20 chloro-
form solution obtained above and aldehyde 21, following the pro-
cedure described for compound 14. Purification by flash
chromatography (ethyl acetate–hexane 5:95) gave steroid 22 as a
mixture of epimers (7:3) at C-22 (70 mg, 64%). From the flash chro-
matography an analytical sample of the major epimer was
a
a
a
a
a
a
obtained and characterized: [
(KBr) max: 3455, 2928, 2855, 1728, 1704, 1246, 1072, 1045,
854 cmÀ1 1H NMR (500.13 MHz, CDCl3) d: 5.38 (1H, bs, H-4),
a]
20 = +108.0 (c = 0.9, methanol); IR
D
a
t
a
;
H-18), 13C NMR (125.77 MHz): 211.3 (C-20), 174.0 (C-25), 140.7
(C-5), 121.3 (C-6), 71.6 (C-3), 62.9 (C-17), 56.9 (C-14), 49.9 (C-9),
44.2 (C-13), 43.8 (C-21), 42.1 (C-4), 38.9 (C-12), 37.2 (C-1), 36.5
(C-10), 33.9 (C-24), 31.80 (C-8), 31.72 (C-7), 31.4 (C-2), 24.5 (C-
22), 24.46 (C-15), 23.1 (C-23), 22.9 (C-16), 21.0 (C-11), 19.3 (C-
19), 13.3 (C-18); HR MS-ESI: calculated for C25H38NaO4 425.2662,
found 425.2678.
4.41 (1H, d, J = 4.7, H-6), 4.35 (1H, m, H-3), 4.04 (1H, m, H-22),
4.02 (1H, d, J = 8.0, H-19a), 3.66 (3H, s, CO2CH3), 3.28 (1H, d,
J = 8.0, H-19b), 2.55 (1H, dd, J = 17.8 and 2.6, H-21a), 2.50 (1H, t,
J = 9.0, H-17), 2.45 (1H, m, H-21b), 2.34 (2H, t, J = 7.4, H-25), 2.15
(1H, m, H-16b), 2.04 (1H, m, H-12b), 1.97 (1H, m, H-1
(1H, m, H-7 ), 1.79 (1H, m, H-2b), 1.78 (2H, m, H-24a and m, H-
8), 1.69 (1H, m, H-24b), 1.65 (2H, m, H-11 and H-16 ), 1.61
(1H, m, H-15b), 1.57 (1H, m, H-9), 1.55 (1H, m, H-2
m, H-23a), 1.43 (1H, m, H-23b), 1.41 (1H, m, H-12
a), 1.89
a
a
a
a), 1.53 (1H,
2.2.6. 3a-t-Butyldimethylsilyloxy-6,19-epoxypregn-4-ene-20-one (19)
a), 1.30 (2H,
Imidazole (47 mg, 0.68 mmol) and t-butyldimethylsilyl chloride
m, H-1b and H-14), 1.27 (1H, m, H-11b), 1.26 (1H, m, H-15
a),
(69 mg, 0.45 mmol) were added successively to a solution of 18
1.24 (1H, m, H-7b), 0.91 (9H, s, ((CH3)3CSi)), 0.67 (3H, s, H-18),