On Steroids
439
EXPERIMENTAL
Melting points were determined on a Kofler block and are uncorrected. Infrared spectra were re-
corded on a Perkin–Elmer PE 580 spectrometer in chloroform, wavenumbers are given in cm−1
.
Proton NMR spectra were taken in deuteriochloroform on an XL-200 (FT mode, 200 MHz) Varian
instrument with tetramethylsilane as the internal reference. Chemical shifts are given in ppm
(δ-scale), coupling constants (J) and multiplet width (W) in Hz. The data were interpreted as the
first-order spectra. The identity of the prepared samples was checked by mixture melting point deter-
mination, thin-layer chromatography (TLC), IR and proton NMR spectra. Preparative TLC was car-
ried out on 200 × 200 mm plates coated with 0.7 mm thick layer of Woelm DC silica gel. The light
petroleum was a fraction boiling at 40 – 62 °C.
3,17-Dioxo-4-androsten-11β-yl Formate3 (IV)
1H NMR spectrum: 8.09 s, 1 H (OCOH); 5.71 d, 1 H (H-4, J(4,6) ≈ 1); 5.64 q, 1 H (H-11α,
J(11α,12α) ≈ J(11α,12β) ≈ J(11α,9α) ≈ 2.5); 1.33 s, 3 H (3 × H-19); 1.06 s, 3 H (3 × H-18).
17β-Hydroxy-3-oxo-4-androsten-11β-yl Formate3 (VI)
1H NMR spectrum: 8.10 s, 1 H (OCOH); 5.71 d, 1 H (H-4, J(4,6) ≈ 1); 5.56 q, 1 H (H-11α,
J(11α,12α) ≈ J(11α,12β) ≈ J(11α,9α) ≈ 2.5); 3.61 dd, 1 H (H-17α, J(16β,17α) = 7.5, J(16α,17α) = 8.5).
3-Oxo-4-androstene-11β,17β-diyl 11-Formate 17-Tosylate (VII)
p-Toluenesulfonyl chloride (2.0 g, 10.5 mmol) was added to a solution of VI (1.6 g, 5.0 mmol) in
pyridine (30 ml) cooled with an ice bath. This mixture was allowed to stand overnight at 40 °C. Then
it was poured onto ice, extracted with ethyl acetate, the organic layer was washed with 5% hydro-
chloric acid, water, 5% aqueous sodium hydrogen carbonate and dried over anhydrous magnesium
sulfate. Evaporation of the solvent in vacuo afforded 2.1 g (86%) of crude product VII, which re-
sisted all attempts at crystallization, even after preparative chromatography on a thin layer of silica
gel, in toluene–ether (1 : 1); [α]D +53° (c 0.9, chloroform). IR spectrum: 1 718 (C=O, formate);
1 666 (C=O, ketone); 1 617 (C=C); 1 168 shoulder (C−O, formate); 1 362, 1 176 (SO2); 1 097,
1
1 020 (C−O). H NMR spectrum: 8.43 s, 1 H (OCOH); 7.75 d, 2 H (H-2′ and H-6′ tosylate, J = 8.5);
7.33 d, 2 H (H-3′ and H-5′, tosylate, J = 8.5); 5.68 d, 1 H (H-4, J(4,6) ≈ 1); 5.46 q, 1 H (H-11α,
J(11α,12α) ≈ J(11α,12β) ≈ J(11α,9α) ≈ 2.5); 4.22 dd, 1 H (H-17α, J(16β,17α) = 7.5, J(16α,17α) = 8.5);
2.45 s, 3 H (CH3, tosylate); 1.28 s, 3 H (3 × H-19); 0.97 s, 3 H (3 × H-18). For C27H34SO6 (468.6)
calculated 66.64% C, 7.04% H, 6.59% S; found: 66.61% C, 7.11% H, 6.47% S.
17α-Hydroxy-3-oxo-4-androsten-11β-yl Formate (V)
A mixture of VII (2.0 g, 4.1 mmol) and sodium nitrite (2.5 g, 36 mmol) in dimethyl sulfoxide
(70 ml) was stirred at 150 °C for 2 h. The mixture was cooled at room temperature, diluted with water
(200 ml) and extracted with ether (3×). The combined organic layers were washed with water (5×),
dried over anhydrous magnesium sulfate, and the solvent was evaporated in vacuo. Chromatography
of the residue (1.8 g) on a column of Silpearl (100 g) in toluene–ether (1 : 1) and then on the thin
layer of silica gel in toluene–ether–methanol (140 : 140 : 1) afforded 80 mg (6%) of V, m.p. 209 –
211 °C (methanol), [α]D +150° (c 0.4, chloroform). IR spectrum: 3 619, 3 435, 3 309 (OH); 1 717
(C=O, formate); 1 662 (C=O, ketone); 1 618 (C=C); 1 193, 1 178 (C−O, formate); 1 057 (C−O,
17-OH); 868 (=C−H). 1H NMR spectrum: 8.40 s, 1 H (OCOH); 5.70 d , 1 H (H-4, J(4,6) ≈ 1);
5.64 q, 1 H (H-11α, J(11α,12α) ≈ J(11α,12β) ≈ J(11α,9α) ≈ 2.5); 3.73 d, 1 H (H-17β, J ≈ 6); 1.31 s, 3 H
Collect. Czech. Chem. Commun. (Vol. 59) (1994)