S. Schwarz et al. / Steroids 64 (1999) 460–471
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1
stirring. After that, the solution was cooled to 0°C and the
reaction was quenched with water (30 ml). 3 N aqueous so-
dium hydroxide solution (200 ml) and aqueous hydrogen per-
oxide solution (200 ml, 30%) were added and the mixture was
stirred at room temperature for 30 min. The product was
isolated by extraction with n-hexane, chromatography (eluent:
cyclohexane/methyl t-butyl ether 10:1) and crystallization
from methanol/water to give compound 10 (42.6 g, 96%). m.p.
88°C–91°C. [␣]D-57°. 1H NMR: 7.40 (d, 8.3, H-1), 6.63 (dd,
8.3, 2.7, H-2), 6.55 (d, 2.7, H-4), 3.89 (m, H-1Ј), 3.80 (m,
H-3Ј), 3.80 (m, H-11), 3.68 (m, H-17), 3.68 (m, H-1Ј), 2.76 (t,
7.1, H-6), 2.42 (dd, 11.9, 4.9, H-12), 0.98 (s, -C(CH3)3), 0.90
(s, -C(CH3)3), 0.70 (s, H-18), 0.19 (s, Si-CH3), 0.06 (s, Si-
CH3), 0.03 (s, Si-CH3). ms: (EI) m/z 574.38702 (M)ϩ.
C33H58O4Si2 (575.00) calculated C 68.93 H 10.17 found C
68.80 H 10.12.
[␣]D-53°. H nmr: 7.39 (d, 8.6, H-1), 6.62 (dd, 8.6, 2.7,
H-2), 6.55 (d, 2.7, H-4), 3.80 (m, H-1Ј), 3.80 (m, H-11),
3.66 (t, 8.0, H-17), 3.58 (dt, 9.3, 6.1, H-1Ј), 2.75 (t, 6.7,
H-6), 2.69 (d, 6.7, H-3Ј), 2.65 (d, 6.7, H-3Ј), 2.40 (dd,
11.8, 5.1, H-12), 2.23 (t, 9.6, H-9), 1.06 (t, 11.8, H-12),
0.98 (s, -C(CH3)3), 0.90 (s, -C(CH3)3), 0.70 (s, H-18),
0.19 (s, Si-CH3), 0.06 (s, Si-CH3), 0.03 (s, Si-CH3). ms:
(EI) m/z 590.36621 (M)ϩ. C33H58O3S Si2 (591.06) cal-
culated C 67.06 H 9.89 S 5.42 found C 66.83 H 9.89 S
5.43.
2.10. Bis-3-[3Ј,17Ј-bis-(t-butyldimethylsilyl)oxy-estra-
1Ј,3Ј,5Ј(10Ј)-trien-11Ј␣-yl]oxypropyl-disulfane (13)
A stirred suspension of compound 12 (14 g, 23.7 mmol)
in dichloromethane (150 ml) and saturated aqueous sodium
hydrogen carbonate solution (150 ml) was treated dropwise
with a solution of iodine (3.18 g, 2.45 mmol) in ethanol (250
ml) until the iodine color did no longer disappear. The
organic phase was separated, dried, and evaporated in
vacuo. After trituration with methanol compound 13 (14 g,
nearly quantitative yield) was obtained. m.p. 83°–90°C.
2.8. S-3-[3Ј,17Ј-Bis-(t-butyldimethylsily)oxy-estra-
1Ј,3Ј,5Ј(10Ј)-trien-11Ј␣-yl]oxypropyl ethanethioate (11)
A 0°C cold solution of triphenylphosphine (20.69 g, 78.6
mmol) and diisopropyl azo-dicarboxylate (15.89 g, 78.6
mmol) in tetrahydrofuran (200 ml) was stirred for 30 min.
Then, in turn, a solution of compound 10 (22.6 g, 39.3
mmol) in tetrahydrofuran (150 ml) and thioacetic S-acid
(5.97 g, 78.6 mmol) in tetrahydrofuran (15 ml) were added.
The resulting mixture was stirred for another 45 min and,
after that, evaporated in vacuo. The residue was treated with
n-hexane/methyl t-butyl ether and the crystals (triph-
enylphosphane oxide) were filtered off. The filtrate was
evaporated in vacuo and the residue was purified by chro-
matography (eluent:toluene) followed by crystallization
from methanol to afford compound 11 (22.5 g, 90.4%). m.p.
1
[␣]D-46°. H nmr: 7.38 (d, 8.3, H-1), 6.62 (dd, 8.3, 2.9,
H-2), 6.55 (d, 2.9, H-4), 3.80 (m, H-1Ј), 3.80 (m, H-11),
3.65 (t, 8.5, H-17), 3.56 (m, 9.3, 6.1, H-1Ј), 2.80 (t, 6.6,
H-6), 2.75 (t, 6.6, H-3Ј), 2.40 (dd, 12.2, 5.0, H-12), 2.23 (t,
9.7, H-9), 1.06 (t, 12, H-12), 0.97 (s, -C(CH3)3), 0.90 (s,
-C(CH3)3), 0.70 (s, H-18), 0.19 (s, Si-CH3), 0.06 (s, Si-
CH3), 0.03 (s, Si-CH3). ms: (EI) m/z 1180.1 (Mϩ).
C66H114O6S2Si4 (1180.11) calculated C 67.18 H 9.74 S 5.43
found C 66.95 H 9.70 S 5.62.
1
77°–80°C. [␣]D-44°. H nmr: 7.37 (d, 8.6, H-1), 6.62 (dd,
2.11. Bis-3-[17Ј-(t-butyldimethylsilyl)oxy-3Јhydroxy-
estra-1Ј,3Ј,5Ј(10Ј)-trien-11Ј␣-yl]oxypropyl-disulfane (14)
8.6, 2.8, H-2), 6.55 (d, 2.8, H-4), 3.76 (m, H-1Ј), 3.76 (m,
H-11), 3.66 (t, 8.4, H-17), 3.52 (dt, 9.1, 5.7, H-1Ј), 2.99 (t,
7.1, H-3Ј), 2.75 (t, 7.0, H-6), 2.38 (dd, 12.1, 5.1, H-12), 2.34
(s, -CO-CH3), 0.98 (s, -C(CH3)3), 0.91 (s, -C(CH3)3), 0.70
(s, H-18), 0.19 (s, Si-CH3), 0.06 (s, Si-CH3), 0.03, (s,
Si-CH3). ms: m/z (EI) 632.37347 (M)ϩ. C35H60O4S Si2
(633.10) calculated C 66.40 H 9.55 S 5.06 found C 66.38 H
9.55 S 5.20.
A mixture of compound 13 (14 g, 11.8 mmol) in a
solution of tetrabutylammonium fluoride (7.6 g, 24
mmol) in tetrahydrofuran (200 ml) was stirred at room
temperature for 30 min. Saturated sodium hydrogen car-
bonate solution (50 ml) was then added, the organic
solvent was evaporated in vacuo and the suspension ex-
tracted with n-hexane. The organic fractions were com-
bined, washed with water, dried, and evaporated in
vacuo. Purification of the residue by chromatography
(eluent:toluene/ethyl acetate 10: 1) followed by crystal-
lization from methanol gave compound 14 (6 g, 93.2%).
m.p. 154°C–157°C. [␣]D-42°. 1H nmr: 7.40 (d, 8.3, H-1),
6.64 (dd, 8.3, 2.6, H-2), 6.55 (d, 2.6, H-4), 5.25 (s,
3-OH), 3.80 (m, H-1Ј), 3.80 (m, H-11), 3.65 (t, 8.2,
H-17), 3.56 (m, H-1Ј), 2.80 (t, 7.0, H-6), 2.73 (t, 6.6,
H-3Ј), 2.39 (dd, 12.0, 5.0, H-12), 2.23 (t, 9.9, H-9), 1.07
(t, 11.0, H-12), 0.90 (s, -C(CH3)3), 0.69 (s, H-18), 0.06 (s,
Si-CH3), 0.03 (s, Si-CH3). ms: (EI) m/z 952.5 (M)ϩ.
C54H86O6S2Si2 (951.58) calculated C 68.16 H 9.11 S
6.74 found C 68.01 H 9.07 S 6.95.
2.9. 3,17-Bis-(t-butyldimethylsilyl)oxy-11␣-(3Ј-
sulfanylpropyl)oxy-estra-1,3,5 (10)-triene (12)
To a stirred solution of compound 11 (13 g, 20.5
mmol) in tetrahydrofuran (150 ml) 1 N lithium alumi-
nium hydride solution in tetrahydrofuran (50 ml, 50
mmol) was added dropwise. After 2 h, the reaction was
quenched with ethyl acetate (100 ml) and water. The
organic phase was separated, washed with water, dried,
and evaporated in vacuo. The residue was purified by
chromatography (eluent:cyclohexane/methyl tert-butyl
ether 10:1) followed by crystallization from methanol to
give compound 12 (10 g, 82.5%). m.p. 102°C–103°C.