A.P.Antonchick et al./ Steroids 69 (2004) 617–628
621
added, and the solvents were removed in vacuo. The residue
was chromatographed on SiO2 with hexane–EtOAc (8:1 ⇒
1:1) to give compound 22 (43 mg, 88%). 1H NMR (C5D5N)
δ: 0.81 (s, 3H, 18-H), 1.06 (s, 3H, 19-H), 1.16 (d, J = 6.6 Hz,
21- or 28-H), 1.27 (d, J = 6.6 Hz, 3H, 28- or 21-H), 3.86 (m,
1H, 3-H), 3.99 (dd, J = 8.4, 1.1 Hz, 22-H), 4.14 (m, 1H, 23-H),
5.40–5.44 (m, 1H, 6-H). 13C NMR (C5D5N) δ: 10.90, 10.92,
12.00, 12.84, 19.67, 21.47, 24.53, 28.42, 30.89, 32.27, 32.65,
36.92, 37.84, 38.15, 40.34, 41.05, 42.41, 43.52, 50.55, 53.11,
57.16, 71.30, 73.11, 74.41, 121.24, 141.99. HRMS calc.
for C28H42D6O3: 438.3980; found: 438.3982. EI-MSm/z
(%): 159 (23), 213 (20), 255 (30), 273 (15), 295 (31), 313
(70), 332 (100), 361 (3), 421 (3) [M + H H2O]+, 438 (26)
[M]•+
minum amalgam was added to a solution of sulfone 24 (1.3 g,
2.26 mmol) in EtOH (50 ml). The mixture was stirred at am-
bient temperature for 15 h, filtered through a short pad of
SiO2 and the solvent was evaporated in vacuo. The residue
was chromatographed on SiO2 (15:1 ⇒ 4:1) to give 673 mg
1
(68%) of ketone 25 as an oil. H NMR δ: 0.74 (s, 3H, 18-
H), 0.80 (d, J = 6.6 Hz, 3H, 28-H), 1.03 (s, 3H, 19-H), 1.08
(d, J = 7 Hz, 3H, 21-H), 2.23 (dd, J = 17, 9.2 Hz, 1H), 2.36
(m, 1H), 2.50 (m, 1H), 2.76 (t, J = 2.9 Hz, 1H, 6-H), 3.32 (s,
3H, OMe). 13C NMR δ: 12.50, 13.15, 16.35, 19.29, 21.56,
22.79, 24.49, 25.01, 27.75, 27.80, 30.59, 33.46, 35.18, 35.36,
40.24, 42.97, 43.48, 46.69, 46.72, 48.14, 49.75, 49.79, 52.08,
55.99, 56.59, 82.45, 214.23. HRMS calc. for C29H42D6O2:
434.4031; found: 434.4023. EI-MSm/z (%): 119 (60), 120
(46), 213 (17), 255 (17), 283 (39), 327 (15), 379 (84), 380
(89), 385 (20), 402 (77) [M-CH3OH]•+, 403 (82), 417 (11),
419 (54) [M CH3]+, 420 (56), 434 (92) [M]•+, 435 (100)
[M + H]+.
2.16. (22R,23R,24S)-[26,27-2H6]24-Methylcholesta-
3,22,23-triol (23)
A solution of 22 (33 mg, 75 mol) in ethanol (15 ml) was
hydrogenated over 5% Pd/C under H2 for 12 h. The reac-
tion mixture was filtered through SiO2, and the solvent was
evaporated. The residue was chromatographed on SiO2 with
hexane–EtOAc (8:1 ⇒ 2:1) to give 23 (32 mg, 97%) as an
oil. 1H NMR δ: 0.67 (s, 3H, 18-H), 0.81 (s, 3H, 19-H), 0.84
(d, J = 7 Hz, 3H, 21- or 28-H), 0.89 (d, J = 6.2 Hz, 3H, 28-
or 21-H), 3.54–3.64 (m, 2H, 3- and 22-H), 3.72 (m, 1H, 23-
H). 13C NMR δ: 10.08, 10.10, 11.87, 11.99, 12.32, 21.27,
24.06, 27.83, 28.68, 31.50, 31.98, 35.56, 36.84, 36.96, 38.19,
40.04, 42.44, 44.78, 52.49, 54.25, 56.37, 71.33, 73.46, 74.88.
HRMS calc. for C28H44D6O3: 440.4137; found: 440.4133.
EI-MSm/z (%): 161 (15), 234 (26), 257 (41), 273 (15),
297 (23), 315 (63), 334 (100), 345 (3), 364 (2), 440 (6)
2.19. Reduction of the ketone (25)
A solution of the ketone 25 (350 mg, 0.81 mmol) in ether
(10 ml) was added to a stirred suspension of LiAlH4 (350 mg,
9.22 mmol) in ether (20 ml). The stirring was continued
at room temperature for 3 h, after which water (0.35 ml),
15% NaOH (0.35 ml), and water (1.05 ml) were consecu-
tively added. The precipitate was filtered off, and the fil-
trate was dried (Na2SO4) and evaporated. The residue was
chromatographed on SiO2 with hexane–EtOAc (10:1 ⇒ 1:1)
to give: (a) (22R,24R)-[26,27-2H6]6-methoxy-24-methyl-
3␣,5-cyclo-5␣-cholestan-22-ol 26 (11%) as an oil. 1H NMR
δ: 0.74 (s, 3H, 18-H), 0.82 (d, J = 6.8 Hz, 3H, 21- or 28-H),
0.92 (d, J = 6.6 Hz, 3H, 28- or 21-H), 1.02 (s, 3H, 19-H), 2.77
(t, J = 2.9 Hz, 1H, 6-H), 3.32 (s, 3H, OMe), 3.74 (ddd, J =
11, 3, 1.2 Hz, 1H, 22-H). 13C NMR δ: 12.28, 13.08, 14.97,
19.29, 21.49, 22.80, 24.29, 24.98, 27.40, 30.53, 33.36, 34.09,
34.12, 35.07, 35.28, 40.28, 42.40, 43.07, 43.39, 48.07, 53.24,
56.11, 56.56, 70.98, 82.38. HRMS calc. for C29H44D6O2:
436.4187; found: 434.4194. EI-MSm/z (%): 213 (16), 255
(10), 261 (12), 284 (34), 364 (14), 381 (48), 382 (46), 404
(42) [M CH3OH]•+, 405 (39), 419 (12) [M + H H2O]+, 421
(30) [M CH3]+, 422 (32), 436 (100) [M]•+, 437 (52) [M
+ H]+; (b) (22S,24R)-[26,27-2H6]6-Methoxy-24-methyl-
3␣,5-cyclo-5␣-cholestan-22-ol 27 (77%) as an oil. 1H NMR
δ: 0.74 (s, 3H, 18-H), 0.83 (d, J = 6.6 Hz, 3H, 21- or 28-
H), 0.89 (d, J = 6.2 Hz, 3H, 28- or 21-H), 2.78 (t, J =
2.6 Hz, 1H, 6-H), 3.33 (s, 3H, OMe), 3.77 (t, J = 6.6 Hz,
1H, 22-H). 13C NMR δ: 11.25, 12.22, 13.11, 15.80, 15.84,
19.30, 21.48, 22.82, 24.14, 24.98, 27.92, 30.59, 31.59, 33.37,
35.12, 35.26, 39.41, 40.31, 42.73, 43.40, 48.01, 52.73, 52.79,
56.46, 56.60, 71.73, 82.43. HRMS calc. for C29H44D6O2:
436.4187; found: 436.4193. EI-MSm/z (%): 213 (21), 255
(17), 261 (20), 284 (52), 364 (23), 381 (85), 382 (87), 404
(84) [M CH3OH]•+, 405 (84), 419 (20) [M + H H2O]+,
421 (53) [M CH3]+, 422 (55), 436 (94) [M]•+, 437 (100)
[M + H]+.
[M]•+
.
2.17. (24R)-[26,27-2H6]6-Methoxy-23-phenylsulfonyl-
24-methyl-3␣,5-cyclo-5␣-cholestan-22-one (24)
Ketone 24 was obtained from the alcohol 18 via Swern
oxidation as described above for preparation of aldehyde
1
3. Compound 24 was isolated as an oil in 87% yield. H
NMR δ: 0.98–1.03 (m, 6H, 18- and 19-H), 3.31, 3.32 (s,
3H, OMe), 4.35–4.40 (m, 1H, 23-H), 7.49–7.95 (m, 5H, Ph).
13C NMR δ: 12.19, 12.61, 13.15, 15.56, 15.95, 16.00, 19.26,
19.30, 21.52, 21.59, 22.73, 22.86, 24.44, 24.58, 24.98, 25.02,
28.22, 30.57, 32.01, 33.44, 33.71, 33.73, 33.84, 35.13, 40.09,
43.43, 48.05, 48.11, 50.95, 51.14, 55.90, 56.58, 60.67, 82.39,
127.93, 128.79, 128.83, 129.26, 129.61, 129.95, 133.48,
133.75.
2.18. (24R)-[26,27-2H6]6-Methoxy-24-methyl-3␣,5-
cyclo-5␣-cholestan-22-one (25)
Aluminum foil was cut into small strips and treated with
15% NaOH for 15 min. Then it was washed twice with wa-
ter, then ethanol, and submerged for 10 min twice in a 0.5%
aqueous mercury(II) chloride solution. The resulting alu-