F. Compostella et al. / Steroids 67 (2002) 111–117
113
flash-chromatography of the crude material 0.160 g of the
starting compound 2, 0.260 g of desogestrel (1), and 0.010
g of 3 were recovered.
8.8; 8.0. PCI-MS: m/z 597 [M ϩ H]ϩ. IR: 1730, 1715,
1635, 900 cmϪ1
.
c) The reaction was carried out and worked as described
in a), without argon atmosphere. After flash chromatogra-
phy of the crude material, 0.170 g of the starting compound
2, 0.227 g of desogestrel (1), and 0.065 g of 3 were recov-
ered.
2.4. 13-Ethyl-16-[2Ј-(des-D-13Љ-ethyl-13Љ-
methoxycarbonyl-11Љ-methylenegon-4Љ-en-14Љ-yl)-
ethyliden]-11-methylenegon-4-en-17-ol (6)
NaBH4 (0.025 g, 0.672 mmol) was added to a solution of
4a (0.2 g, 0.336 mmol) in methanol (20 ml). The reaction
was stirred for 1.5 h at room temperature and then quenched
by the addition of water. After extraction with ethyl acetate
(3 ϫ 20 ml), the organic layer was dried (Na2SO4) and
concentrated in vacuo to give crude 6. Purification by flash
chromatography (hexane/ethyl acetate 8.5:1.5) gave 0.136
g of the alcohol 6. Foam. [␣]D ϭ –5 (c 1; CHCl3). 1H-NMR:
5.45 and 5.42 (2 br s, 2H, 2 H-4); 5.38 (dd, 1H, J 2.0 Hz, J
4.5 Hz, H-1Ј); 4.93, 4.81, 4.74 and 4.70 (4 s, 4H, 2 ϭCH2);
3.93 (br s, 1H, H-17); 3.59 (s, 3H, COOCH3); 2.81 (d, 1H,
J 12.0 Hz, Ha-12); 2.51 (ddd, 1H, J 17.0 Hz, J 7.5 Hz, J 2.0
Hz, Ha-2Ј); 2.38 (d, 1H, J 12.5 Hz, Ha-12); 0.86 and 0.84 (2
t, 6H, 2 CH3). 13C-NMR: 174.2; 146.5; 145.8; 143.0; 139.1;
138.8; 128.9; 120.9; 120.3; 107.9; 106.4; 85.7; 54.6; 53.9;
51.0; 49.0; 47.4; 45.5; 45.4; 45.1; 43.8; 43.4; 41.3; 36.0;
35.9; 35.0; 34.9; 34.3; 31.2; 30.9; 28.5; 28.1; 27.8; 25.1; 25.0;
21.9; 21.3; 21.2; 18.2; 8.4; 7.8. PCI-MS: m/z 599 [M ϩ H]ϩ.
2.2. 13-Ethyl-16-[2Ј-(des-D-13Љ-carboxy-13Љ-ethyl-11Љ-
methylenegon-4Љ-en-14Љ-yl)-ethyliden]-11-methylenegon-4-
en-17-one (4)
Potassium tert-butoxide (0.395 g, 3.52 mmol) was added
to a solution of 2 (0.5 g, 1.76 mmol) in tetrahydrofuran (11
ml; the solvent was previously bubbled with air for 10 min)
at 0°C. After 5 h at 0°C the reaction was incubated over-
night at Ϫ20°C. The yellow mixture was then quenched
with acetic acid (1 ml) and diluted with ethyl acetate (30
ml). The resulting mixture was washed with water (3 ϫ 30
ml) and dried over Na2SO4. After evaporation of the sol-
vent, the residue was subjected to flash chromatography
(toluene/AcOEt 9:1) to yield 0.305 g of pure 4 as an
amorphous solid and 0.130 g of a mixture of very polar
products in which tars were prevailing and which were not
1
further characterized. 4: [␣]D ϭ ϩ11 (c 0.5; CHCl3). H-
IR: 3400, 1725, 1635, 900 cmϪ1
.
NMR: 6.51 (dd, 1H, J 2.0 Hz, J 2.0 Hz, H-1Ј); 5.48 and 5.44
(2 br s, 2H, 2 H-4); 4.91, 4.84, 4.82 and 4.75 (4 s, 4H,
2 ϭCH2); 2.85 (ddd, 1H, J 15.5 Hz, J 6.5 Hz, J 2.0 Hz,
Ha-2Ј); 2.60 and 2.39 (2 d, 2H, J 12.5 Hz, 2 Ha-12); 0.83 and
0.68 (2 t, 6H, 2 CH3). 13C-NMR: 207.3; 179.3; 146.1;
145.4; 142.3; 139.3; 139.0; 137.2; 121.6; 121.1; 110.0;
107.8; 55.1; 54.3; 51.7; 49.7; 46.4; 46.0; 45.5; 43.3; 41.2;
39.8; 36.5; 36.4; 35.4; 35.2; 34.9; 31.2; 31.1; 29.1; 28.7;
27.1; 25.6; 25.5; 22.6; 21.8; 18.8; 8.1; 7.3. EI-MS: m/z 582
[M]ϩ. UV: max247 nm (⑀ ϭ 13 000). IR: 1725, 1710, 1635,
2.5. X-ray crystallography
Crystal structure of C22H30O2 (3). The crystals were
colorless needles obtained by recrystallization from meth-
ylene chloride/methanol. A summary of the crystal data,
data collection, and structure refinement is presented in
Table 1. The structure was solved by direct methods, and
the E-map revealed correctly all the nonhydrogen atoms in
the molecule. The hydrogen atoms were located on a three-
dimensional difference Fourier synthesis and compared
with those calculated from the geometry of the molecule.
The subsequent least–squares refinement included the hy-
drogen atoms in fixed positions with the same isotropic
thermal parameter as the atom to which they were attached.
The observed reflections were given unit weights.
900 cmϪ1
.
2.3. 13-Ethyl-16-[2Ј-(des-D-13Љ-ethyl-13Љ-
methoxycarbonyl-11Љ-methylenegon-4Љ-en-14Љ-yl)-
ethyliden]-11-methylenegon-4-en-17-one (4a)
An etheral solution of diazomethane was added dropwise
to a solution of 4 (0.260 g, 0.446 mmol) in diethyl ether (6
ml) at 0°C until the yellow color persisted. After evapora-
tion of the solvent, the residue was purified by flash chro-
matography (toluene) to afford 4a (0.238 g). Foam. [␣]D ϭ
–6 (c 1; CHCl3). 1H-NMR: 6.52 (dd, 1H, J 2.0 Hz, J 2.0 Hz,
H-1Ј); 5.48 and 5.44 (2 br s, 2H, 2 H-4); 4.91, 4.83 and 4.74
(3 s, 4H, 2 ϭCH2); 3.57 (s, 3H, COOCH3); 2.86 (ddd, 1H,
J 15.5 Hz, J 6.5 Hz, J 2.0 Hz, Ha-2Ј); 2.61 and 2.39 (2 d, 2H,
J 12.5 Hz, 2 Ha-12); 0.82 and 0.68 (2 t, 6H, 2 CH3).
13C-NMR: 208.0; 146.9; 146.3; 143.2; 140.0; 139.8; 137.9;
122.4; 121.7; 110.7; 108.4; 55.8; 55.1; 52.5; 52.3; 50.1;
47.2; 46.7; 46.2; 43.8; 41.9; 40.5; 37.3; 37.1; 36.2; 35.9;
35.7; 31.9; 29.7; 29.4; 27.8; 26.3; 26.2; 23.5; 22.5; 19.5;
The fractional atomic coordinates are presented in Table
2. The molecule conformation and the atomic labeling
scheme [13] are shown in Fig. 1.
The conformations of A, B, C and D rings were as
follows: Ring A, half-chair with puckering parameters [14]
Q ϭ 0.500, ϭ 128.8°, and ϭ 143.2° (theoretical values,
ϭ 135.0° and ϭ 135.0°); the atoms C3, C4, C5, and
C10 were nearly coplanar; Ring B, chair with puckering
parameters Q ϭ 0.571, ϭ 2.5°, and ϭ 349.6° (theoret-
ical values ϭ 0°, and ϭ 360.0°); Ring C, chair with
puckering parameters Q ϭ 0.670, ϭ 6.0°, and ϭ 194.4°
(theoretical values ϭ 0°, and ϭ 180.0°). Ring D, twist
with puckering parameters Q ϭ 0.516, and ϭ 339.1