SYNTHESIS AND MOLECULAR STRUCTURE OF D-HOMO-B-NOR-8α ANALOGS
1515
mixture was heated for 20 min under reflux, quickly
cooled, and left to stand for 24 h at 5°C. The precip-
itate was filtered off, washed on a filter with methanol,
and recrystallized from chloroform–methanol (1:8).
Yield 2.65–2.75 g (56–58%), mp 133–133.5°C. No de-
pression of the melting point was observed on mixing
samples of VIII prepared as described in a and b; their
1H NMR spectra were also identical.
45 ml of anhydrous dioxane. The mixture was stirred
until it became homogeneous, 4.0 g of methyl iodide
was added in portions, and the mixture was heated for
3 h under reflux, cooled to room temperature, poured
into 150 ml of water, and extracted with methylene
chloride (4×50 ml). The extracts were combined,
washed with 20% acetic acid and then with water until
neutral washings, and evaporated, and the residue was
recrystallized from methanol. Yield 0.91–0.97 g (55–
1-Methoxy-4-methyl-D-homo-B-nor-8α-estra-
1,3,5(10)-trien-17a-one (II). a. A 600-ml steel high-
pressure reactor was charged with a solution of 4.75 g
of compound VIII in 270 ml of benzene, 10 g of
freshly prepared Raney nickel [15] (thoroughly washed
with benzene) was added, hydrogen was supplied to
a pressure of 160 atm, the mixture was heated to 60°C,
and stirring was turned on. The hydrogenation process
was maintained continuous so that the temperature of
the reaction mixture by the end of the process did not
exceed 130°C. When 100–120 l of hydrogen was
absorbed, the hydrogenation products were oxidized
with the Sarett reagent prepared from 5 g of chromium
trioxide and 80 ml of pyridine [1]. After appropriate
treatment, steroid II was purified by recrystallization
from chloroform–methanol (1:6). Yield 1.26 g (26%),
1
59%), mp 230–234°C. H NMR spectrum, δ, ppm:
7.09 (1-H), 6.70 (2-H), 6.77 (4-H), 2.81 (6α-H), 2.94
(6β-H), 2.58 (8α-H), 2.84 (9α-H), 1.82 (11α-H), 1.28
(11β-H), 1.36 (12α-H), 1.94 (12β-H), 1.92 (14α-H),
1.64 (15α-H), 2.01 (15β-H), 1.68 (16α-H), 1.89
(16β-H), 1.19 (18-H), 1.11 (17α-CH3), 1.20 (17β-CH3),
3.78 (CH3O). 13C NMR spectrum, δC, ppm: 123.94 (C1),
111.74 (C2), 158.48 (C3), 110.51 (C4), 143.55 (C5),
33.46 (C6), 45.17 (C8), 43.81 (C9), 140.88 (C10), 26.36
(C11), 32.78 (C12), 47.53 (C13), 42.46 (C14), 22.98 (C15),
38.62 (C16), 43.87 (C17), 219.71 (C17a), 18.02 (C18),
28.39 (17α-CH3), 28.26 (17β-CH3), 55.25 (CH3O).
Mass spectrum, m/z (Irel, %): 312 (92) [M]+, 284 (7.5),
240 (13), 228 (47), 213 (46), 199 (13.5), 185 (14.5),
171 (13.5), 160 (32), 146 (100). Found, %: C 80.73,
80.95; H 9.00, 9.05. C21H28O2. Calculated, %: C 80.73;
H 9.03. M 312.45.
1
mp 115–116°C. H NMR spectrum, δ, ppm: 6.62
(2-H), 6.94 (3-H), 2.78 (6α-H), 2.84 (6β-H), 2.49
(8α-H), 3.13 (9α-H), 2.08 (11α-H), 1.21 (11β-H), 1.59
(12α-H), 1.73 (12β-H), 1.85 (14α-H), 1.65 (15α-H),
2.01 (15β-H), 1.73 (16α-H), 2.12 (16β-H), 2.27
(17α-H), 2.71 (17β-H), 1.24 (18-H), 2.20 (1-CH3), 3.80
(CH3O). 13C NMR spectrum, δC, ppm: 153.79 (C1),
108.26 (C2), 127.79 (C3), 125.95 (C4), 142.34 (C5),
32.34 (C6), 44.70 (C8), 42.02 (C9), 135.50 (C10), 23.85
(C11), 31.14 (C12), 48.34 (C13), 44.12 (C14), 25.86 (C15),
25.25 (C16), 37.64 (C17), 215.47 (C17a), 17.48 (C18),
17.51 (4-CH3), 55.05 (CH3O). Mass spectrum, m/z
(Irel, %): 298 (100) [M]+, 265 (12), 242 (5), 227 (51),
213 (13), 199 (16), 185 (11), 173 (28), 160 (65), 145
(18). Found, %: C 80.67; H 8.67. C20H26O2. Calculat-
ed, %: C 80.50; H 8.78.
17,17-Dimethyl-D-homo-B-nor-8α-estrone (IX).
Compound XI, 0.80 g, was dissolved in 35 ml of anhy-
drous acetic acid, 20 ml of 45% hydrobromic acid was
added, and the mixture was heated for 2.5 h on a boil-
ing water bath under stirring, cooled to room tempera-
ture, poured into 100 ml of cold water, and extracted
with chloroform (3×75 ml). The extract was washed
with water until neutral washings, dried over anhy-
drous sodium sulfate, and filtered, the solvent was
removed under reduced pressure, and the residue was
crystallized from hexane–dioxane (2:1). Yield 0.36 g
(47%), mp 277–281°C. Mass spectrum, m/z (Irel, %):
298 (100) [M]+, 280 (6), 270 (7), 265 (6), 226 (32),
214 (46), 199 (67), 186 (16), 185 (18), 171 (18), 156
(21), 146 (44), 132 (88). Found, %: C 80.44; H 8.90.
C20H26O2. Calculated, %: C 80.49; H 8.78. M 298.42.
b. Raney nickel, 5 g, was added to a solution of 4 g
of steroid VIII in 270 ml of isopropyl alcohol, and the
mixture was stirred in a steel high-pressure reactor at
100–110°C under a hydrogen pressure of 100 atm. The
mixture was then treated as described above in a. Yield
1.18 g (29%), mp 115–116°C. No depression of the
melting point was observed on mixing samples of II
prepared as described in a and b.
REFERENCES
1. Shavva, A.G., Selivanov, S.I., Starova, G.L., Boronoe-
va, T.R., Ishchenko, I.V., Gluzdikov, I.A., Sharets-
kii, A.N., Isaeva, V.G., and Surinov, B.P., Bioorg. Khim.,
2002, vol. 28, p. 242.
17,17-Dimethyl-D-homo-B-nor-8α-estrone
methyl ether (XI). Potassium tert-butoxide, 3.3 g, was
added to a solution of 1.5 g of compound X [7] in
2. Brattsand, R., Holmdahl, R., Jansson, L., Loncar, M., and
Pettersson, L., WO Patent Appl. no. 9708188; Chem.
Abstr., 1997, vol. 126, no. 225448x.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010