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E.J. Tavares da Silva et al. / Steroids 67 (2002) 311–319
9.0, J3,2 5.0, 3-H), 3.71 (1H, dd, J4␣,5 11.0–12.0, J4␣,3
9.0, 4␣-H); 13C NMR (125 MHz, CDCl3) ␦: 13.9 (C-18),
23.6 (C-19), 48.6 (C-5), 72.7 (C-4), 76.7 (C-3), 220.4 (C-
17); EIMS m/z 306 (Mϩ, 83.5%); HRMS calculated for
C19H30O3 (Mϩ): 306.2195; Found: 306.2210.
was washed with 10% aq. NaHCO3 (2 ϫ 40 ml), water (4 ϫ
40 ml), dried (MgSO4) and evaporated to dryness yielding
the crude diosphenol 3-hydroxy-5␣-androst-2-ene-4,17-di-
one 4 (199 mg, 98%) as the only detected product. This pale
yellow solid could not be crystallized, and an analytical
sample was purified by column chromatography [silica gel;
ethyl acetate-light petroleum (b.p. 60–80°C) (1:1)].
Diol 9: White solid from acetone-hexane mp 202–204°C
(lit [13] 201–203°C);
(KBr)/cmϪ1 3460 (OH), 1735
max
1
(C ϭ O); H NMR (500 MHz, CD3OD) ␦: 0.86 (3H, s,
18-H3), 0.97 (3H, s, 19-H3), 2.07 (1H, ddd, J16␣,16 19.0,
J16␣,15␣/15 9.5, 16␣-H), 2.26 (1H, dd, J4␣,4 15.0, J4,3␣ 3.0,
4-H), 2.44 (1H, dd, J16,16␣ 19.0, J16,15 9.0, 16-H), 4.11
(1H, dddd, J3␣,2␣ 3.0, J3␣,2 3.0, J3␣,4␣ 3.0, J3␣,4 3.0,
3␣-H); 13C NMR (125 MHz, CDCl3) ␦: 13.8 (C-18), 17.0
(C-19), 37.1 (C-4), 68.1 (C-3), 75.1 (C-5), 220.5 (C-17);
EIMS m/z 306 (Mϩ, 14.6%); HRMS calculated for
C19H30O3: 306.2195; Found: 306.2184.
Diosphenol 4: Amorphous solid,
(KBr)/cmϪ1 3400
max
1
(OH), 1740 (C ϭ O), 1675 (C ϭ O), 1650 (C ϭ C); H
NMR (500 MHz, CDCl3) ␦: 0.88 (3H, s, 18-H3), 0.93 (3H,
s, 19-H3), 5.85 (1H, s, disappeared with D2O, 2-OH), 5.96
(1H, dd, J2,1 3.0, J2,1 7.0, 2-H); 13C NMR (50.3 MHz,
CDCl3) ␦: 13.2 (C-18), 13.7 (C-19), 113.9 (C-2), 145.9
(C-3), 196.8 (C-4), 220.7 (C-17); EIMS m/z 302 (Mϩ,
100%); Elemental analysis calculated for C19H26O3: C,
75.46; H, 8.67. Found: C, 75.46; H, 8.97.
The same oxidation reaction conditions used for the
vic-diol 3 were applied to diol 7 giving a mixture with a
variable composition (1:2 to 2:1 by NMR) of the triketone
5-androstane-3,4,17-trione 10 and the diosphenol 3-hy-
droxy-5-androst-2-ene-4,17-dione 11. The unstable com-
pounds 10 and 11 couldn’t be separated because of their
rapid conversion into diosphenol 5 and were identified in
2.4.3. 3,4␣-Dihydroxy-[3␣,5-2H2]-5-androstan-17-one
16, 3␣,4-dihydroxy-[3,5-2H2]-5-androstan-17-one 17
and 3,5-dihydroxy-[3␣,4-2H2]-androstan-17-one 18
Prepared as 7, 8 and 9, but using the deuterium labeled
epoxide 15, as starting material. In these conditions the
isolated products were the labeled trans-diaxial and trans-
diequatorial vic-diols 16 and 17 and the labeled non-vicinal
diol 18 with identical yields. The position of the deuterium
1
the mixture only by H NMR.
1
Triketone 10: H NMR (500 MHz, CDCl3) ␦: 0.86 (3H,
1
label was unambiguously confirmed by H and 13C NMR.
s, 18-H3), 1.17 (3H, s, 19-H3), 2.65 (1H, ddd, J2␣,2 18.0,
J2␣,1 15.0, J2␣,1␣ 6.0, 2␣-H), 2.77 (1H, ddd, J2,2␣ 18.0,
J2,1 5.0, J2,1␣ 2.5, 2-H).
Labeled vic-diol 16: 1H NMR (300 MHz, CDCl3) ␦: 0.87
(3H, s, 18-H3), 0.99 (3H, s, 19-H3), (3␣-2H, not visible),
3.79 (1H, s, 4-H); 13C NMR (75.6 MHz, CDCl3) ␦: 13.6
(C-18), 22.5 (C-19), (C-5, not visible), (C-3, not visible),
76.2 (C-4), 221.6 (C-17).
Diosphenol 11: 1H NMR (500 MHz, CDCl3) ␦: 0.86 (3H,
s, 18-H3), 1.17 (3H, s, 19-H3), 5.91 (1H, dd, J2,1␣ 7.0, J2,1
3.0, 2-H), 6.02 (1H, broad s, disappeared with D2O, 3-OH).
Applying the same oxidation reaction conditions to the
vic-diol 8, the diosphenol 11 was the only product detected
in the crude obtained from the reaction. Attempts to recrys-
tallize this compound where unsuccessful also due to its
rapid conversion into diosphenol 5 and it was identified only
Labeled vic-diol 17: 1H NMR (300 MHz, CDCl3) ␦: 0.87
(3H, s, 18-H3), 1.01 (3H, s, 19-H3), (3-2H, not visible),
3.71 (1H, s, 4␣-H); 13C NMR (75.6 MHz, CDCl3) ␦: 13.8
(C-18), 23.4 (C-19), (C-5, not visible), 72.5 (C-4), 76.7
(C-3, not visible), 221.3 (C-17).
1
1
Labeled diol 18: H NMR (300 MHz, CD3OD) ␦: 0.87
by IR, H and 13C NMR.
(3H, s, 18-H3), 0.98 (3H, s, 19-H3), 2.23 (1H, s, 4-H),
(3␣-2H, not visible); 13C NMR (75.6 MHz, CDCl3) ␦: 13.7
(C-18), 17.0 (C-19), (C-4, not visible), (C-3 not visible),
75.0 (C-5), 221.1 (C-17).
Diosphenol 11: Amorphous slightly yellow solid,
max
(KBr)/cmϪ1 3340 (OH), 1735 (C ϭ O), 1670 (C ϭ O), 1655
1
(C ϭ C); H NMR (500 MHz, CDCl3) ␦: 0.86 (3H, s,
18-H3), 1.17 (3H, s, 19-H3), 5.91 (1H, dd, J2,1␣ 7.0, J2,1
3.0, 2-H), 6.02 (1H, broad s, disappeared with D2O, 3-OH);
13C NMR (50.3 MHz, CDCl3) ␦: 13.8 (C-18), 23.0 (C-19),
113.2 (C-2), 146.4 (C-3), 196.8 (C-4), 220.5 (C-17).
Oxidation of the diol 9 with the same reaction conditions
above described gives the hydroxyketone 5-hydroxyan-
drostane-3,17-dione 12 which is converted into the enone
androst-4-ene-3,17-dione 13 during the work-up procedure.
Analytical samples of 12 and 13 were isolated by prepara-
tive TLC [silica gel; ethyl acetate-n-hexane (1:1)]. Attempts
to recrystallize compound 12 where unsuccessful due to its
conversion into enone 13 and it was identified only by IR,
1H and 13C NMR.
2.5. General procedure for the DMSO oxidation of diols
3, 7, 8, 9
To a stirred and cooled (Ϫ60°C) mixture of dimethyl-
sulfoxide (DMSO) (0.15 ml, 2.11 mmol) in dichlorometh-
ane (9 ml) under nitrogen, trifluoroacetic anhydride (TFAA)
(0.27 ml, 1.91 mmol) was added dropwise. After 10 min a
solution of diol 3 (203 mg, 0.66 mmol) in a mixture of
dichloromethane and dimethylsulfoxide (1 ml) was added
and stirred until the steroid was consumed (3 h, TLC con-
trol). Triethylamine (Et3N) (0.62 ml, 4.41 mmol) was then
added and after 15 min at Ϫ60°C the temperature was raised
at 5°C. The solution was poured into 2N HCl (20 ml) and
extracted with dichloromethane (3 ϫ 20 ml). The extract
Hydroxyketone 12: Amorphous white solid, max (KBr)/
1
cmϪ1 3480 (OH), 1700–1730 (C ϭ O); H NMR (500
MHz, CDCl3) ␦: 0.90 (3H, s, 18-H3), 1.03 (3H, s, 19-H3),