cooling to 20 ЊC the mixture was treated with NaBH4 (200 mg,
5.3 mmol) and stirred for 30 min. It was then diluted with ethyl
acetate and washed with water to give, after FCC with 7.5%
MeOH–CH2Cl2 as eluent, the triol 21 (73 mg, 48%), mp 227–
232 ЊC (from MeOH–acetone–LP) (lit.,10 233–234 ЊC from
acetone). In a separate reaction as above the aldehyde 20 (40 mg
from 100 mg, 40%), mp 163–167 ЊC (from acetone–LP) was
isolated by FCC with 30% acetone–LP as eluent but proved to
be too unstable for further purification.
heated under reflux for 5 min, it was filtered through Celite and
evaporated to give a residue which on FCC (5% acetone–LP)
gave the unsaturated dione 27a (120 mg, 24%), mp 146–149 ЊC
(from Et2O–LP) (Found: C, 73.4; H, 7.8. C21H26O4 requires C,
73.6; H, 7.65%).
(19S)-19-Hydroxy-5â,19-cycloandrost-1-ene-3,17-dione 27b
Trimethylsilyl trifluoromethanesulfonate (3.5 cm3, 0.018 mmol)
was added to a stirred solution of the saturated dione 3b (748
mg, 2.17 mmol) and Et3N (6 cm3, 42 mmol) in dry DMF cooled
in an ice-bath. After 2 h the mixture was poured into Et2O and
the organic layer separated and washed with brine to give after
FCC (8% EtOAc–LP) fractions (462 mg, 0.99 mmol) of the
2- and 3-enol silyl ethers 26b (H-2/4, 2.3:1); δ(CDCl3) 3.70 (s,
19-H in 3-enol) and 3.79 (s, 19-H in 2-enol). These fractions
were dissolved in MeCN (30 cm3) and treated with Pd(OAc)2
(228 mg, 1.02 mmol) at 40 ЊC for 30 min and worked up as
described for 27a to give the unsaturated dione 27b (238 mg,
32%), mp 203–205 ЊC (from CH2Cl2–EtOAc) (Found: C, 73.65;
H, 7.9. C21H26O4 requires C, 73.6; H, 7.65%).
3â,17â-Dihydroxy-5â-androstan-19-al 22 and 5â-androstane-
3â,17â,19-triol 23
The 19(R)-triol 15 (100 mg, 0.33 mmol) was stirred with THF
(15 cm3) containing 12 aqueous HCl (0.5 cm3) at 25 ЊC for 24
h after which the mixture was diluted with EtOAc (100 cm3),
washed with water, and evaporated under reduced pressure at
40 ЊC. The residue was taken up in MeOH (10 cm3) and treated
with NaBH4 (200 mg, 5.29 mmol) at 25 ЊC for 30 min. EtOAc
(100 cm3) was added to the mixture which was then washed
with water. Work-up provided a residue which on FCC with
7.5% MeOH–CH2Cl2 as eluent, gave the triol 23 (26 mg, 25%),
mp 220–221 ЊC from (MeOH–acetone–LP) or mp 220–221.5 ЊC
(from EtOAc) [lit.,11 230–232 ЊC (from EtOAc)]. Because of the
mp difference elemental analysis was carried out (Found: C,
73.7; H, 10.3. C19H32O3 requires C, 74.0; H, 10.5%). In a separ-
ate reaction the aldehyde 22 (39 mg from 100 mg, 39%), mp
170–174 ЊC (from acetone–LP) was obtained by FCC with 20%
acetone–LP as eluent, but proved to be too unstable for further
purification.
5â,19-Cycloandrost-1-ene-3,17-dione 28
Treatment of 19-hydroxyandrost-4-ene-3,17-dione (500 mg,
1.65 mmol) with diethyl(2-chloro-1,1,2-trifluoroethyl)amine as
described by Knox et al.14 gave the 1-ene, mp 184–186 ЊC (120
mg, 25%) (lit.,14 mp 185–187 ЊC).
Acknowledgements
We thank the Medical Research Council of Canada for finan-
cial support. H. Majgier-Baranowska has been a recipient for a
Leslie F. Buggey Graduate Scholarship.
5â-Androstane-3â,17â,19-triol 23
The 19(S)-triol 18 (150 mg, 0.49 mmol) in THF (15 cm3) con-
taining 12 aqueous HCl (0.5 cm3) was set aside at 20 ЊC for 49
h after which it was worked up as described for the preparation
of compound 23 from the triol 15, to give a residue which was
taken up in MeOH and treated with NaBH4 (200 mg, 5.29
mmol). The mixture was stirred for 30 min and worked up to
give the triol 23 (69 mg, 45%), mp 220–221 ЊC (from MeOH–
acetone–LP).
References
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The 19(S)-triol 18 (150 mg, 0.49 mmol) was dissolved in 0.5
methanolic KOH (10 cm3) and the solution heated to reflux for
72 h; it was then cooled to 20 ЊC and treated with NaBH4 (200
mg, 5.3 mmol), the mixture being stirred for 30 min before
dilution with EtOAc. After this, the mixture was washed with
water to give on FCC with 7.5% MeOH–CH2Cl2 as eluent the
triol 25 (22 mg, 15%), mp 194–195 ЊC (from acetone–LP)
(Found: C, 73.9; H, 10.6. C19H32O3 requires C, 74.0; H, 10.5%)
and the triol 21 (45 mg, 30%), mp 227–231 ЊC (from MeOH–
acetone–LP).
(19R)-19-Hydroxy-5â,19-cycloandrost-1-ene-3,17-dione 27a
The saturated dione 2b (500 mg, 1.45 mmol) in CH2Cl2 (2.5
cm3) was added in portions over 5 min, to a stirred and cooled
(acetone–solid CO2 bath) mixture of Pri2EtN (230 µl, 1.9 mmol)
and trimethylsilyl trifluoromethanesulfonate (340 µl, 0.39 mmol)
in CH2Cl2 (10 cm3), under Ar. After the mixture had been
stirred for a further 1.5 h it was treated with MeOH (0.5 cm3) to
destroy the excess of reagent and diluted with further ether.
It was then washed with brine, dried and evaporated to give
a residue which on FCC (18% Et2O–0.2% Et3N in LP) gave
fractions of the 2- and 3-enol silyl ethers 26a (464 mg) (HC-2/4,
6:1:1); δ(CDCl3) 4.66 (ddd, J 6.1, 2.4, 2.4) and 5.30 (d, J 2,
allylic coupling). Pd(OAc)2 (263 mg, 1.17 mmol) in MeCN
(5 cm3) was added to the enol mixture dissolved in MeCN
(30 cm3) at 20 ЊC and the solution stirred at 50 ЊC for 5.5 h.28 It
was then evaporated under reduced pressure, diluted with Et2O
and treated with activated carbon. After the mixture had been
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J. Chem. Soc., Perkin Trans. 1, 1997
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