T. V. Kurzchalia, H.-J. Knölker et al.
FULL PAPER
tion of the trimethylsilyl enol ether (12) (500 mg, 1.09 mmol) in
diethyl ether (20 mL). After stirring of the reaction mixture for
30 min at room temperature under an argon atmosphere and cool-
ing to –78 °C, methyl cyanoformate (104 µL, 11 mg, 1.31 mmol)
was added. The mixture was warmed to room temperature and
stirred for 24 h. Water (10 mL) and diethyl ether (5 mL) were added
and stirring was continued for further 10 min. After addition of
water (15 mL) the phases were separated and the aqueous phase
was extracted three times with ether. The combined organic layers
were washed with brine, dried with sodium sulfate, and the solvent
was evaporated. Purification of the residue by flash chromatog-
raphy (petroleum ether/diethyl ether, 10:1) on silica gel afforded 17
as colorless crystals, yield: 350 mg (72%), m.p. 159–164 °C. IR
2849, 1717, 1439, 1282, 1253, 1073, 1027, 734, 721, 569 cm–1. 1H
NMR (500 MHz, CDCl3): δ = 0.63 (s, 3 H), 0.65 (m, 1 H), 0.80–
0.88 (m, 1 H), 0.82 (s, 3 H), 0.84 (d, J = 6.6 Hz, 3 H), 0.85 (d, J =
6.6 Hz, 3 H), 0.88 (d, J = 6.5 Hz, 3 H), 0.90–1.18 (m, 10 H), 1.19–
1.36 (m, 7 H), 1.44–1.53 (m, 4 H), 1.63 (dq, J = 13.1, 3.1 Hz, 1 H),
1.71–1.85 (m, 4 H), 1.95 (dt, J = 12.6, 3.3 Hz, 1 H), 2.32 (t, J =
10.8 Hz, 1 H), 3.69 (s, 3 H), 3.78 (dt, J = 4.6, 10.7 Hz, 1 H) ppm.
13C NMR and DEPT (125 MHz, CDCl3): δ = 12.03 (CH3), 12.87
(CH3), 18.83 (CH3), 21.19 (CH2), 22.54 (CH3), 22.80 (CH3), 23.79
(CH2), 24.12 (CH2), 25.73 (CH2), 27.99 (CH), 28.20 (CH2), 30.30
(CH2), 31.59 (CH2), 35.02 (CH), 35.60 (C), 35.75 (CH), 36.12
(CH2), 36.41 (CH2), 39.48 (CH2), 39.90 (CH2), 42.49 (C), 47.25
(CH), 51.47 (CH3), 53.65 (CH), 54.12 (CH), 56.17 (CH), 56.28
(CH), 72.84 (CH), 175.85 (C=O) ppm. MS (180 °C): m/z (%) = 446
(ATR): ν = 2932, 2861, 1741, 1711, 1464, 1440, 1373, 1266, 1175,
˜
1025, 737 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.66 (s, 3 H), (100) [M+], 431 (19), 428 (24), 414 (11), 413 (21), 292 (40), 291 (58),
0.78 (m, 1 H), 0.84 (d, J = 6.6 Hz, 3 H), 0.85 (d, J = 6.6 Hz, 3 H),
275 (24), 274 (37), 273 (61). HRMS: m/z [M+] calcd. for C29H50O3:
0.89 (d, J = 6.5 Hz, 3 H), 0.91–1.18 (m, 10 H), 1.03 (s, 3 H), 1.19– 446.3760; found 446.3774.
1.45 (m, 7 H), 1.47–1.57 (m, 4 H), 1.67 (dq, J = 13.2, 3.4 Hz, 1 H),
4α-Carboxy-5α-cholestan-3β-ol (19): The ester 18b (50 mg,
1.81 (m, 1 H), 1.92 (m, 1 H), 1.99 (m, 2 H), 2.40 (m, 2 H), 3.25 (d,
J = 12.9 Hz, 1 H), 3.73 (s, 3 H) ppm. 13C NMR and DEPT
(125 MHz, CDCl3): δ = 12.05 (CH3), 12.40 (CH3), 18.64 (CH3),
21.32 (CH2), 22.55 (CH3), 22.81 (CH3), 23.80 (CH2), 24.14 (CH2),
26.90 (CH2), 28.00 (CH), 28.21 (CH2), 31.34 (CH2), 35.11 (CH),
35.49 (C), 35.76 (CH), 36.11 (CH2), 37.69 (CH2), 37.85 (CH2),
39.48 (CH2), 39.79 (CH2), 42.54 (C), 48.71 (CH), 51.92 (CH3),
53.69 (CH), 56.13 (CH), 56.17 (CH), 60.04 (CH), 170.60 (C=O),
206.27 (C=O) ppm. MS (100 °C): m/z (%) = 444 (87) [M+], 426
(34), 413 (25), 412 (35), 369 (27), 316 (26), 315 (46), 314 (27), 290
(31), 289 (78), 258 (20), 257 (34), 231 (43), 229 (62), 149 (53), 129
(100). HRMS: m/z [M+] calcd. for C29H48O3: 444.3603; found
444.3621.
112 µmol) was added to a solution of potassium hydroxide in meth-
anol (20%, 12 mL), refluxed for 20 h, and cooled to room tempera-
ture. Water (70 mL) was added and the solution was acidified by
addition of hydrochloric acid. The mixture was extracted three
times with ethyl acetate, the combined organic layers were washed
with water and dried with magnesium sulfate. After evaporation of
the solvent 19 was isolated as colorless crystals, yield 45 mg (93%),
m.p. 276 °C. IR (ATR): ν = 3315, 2930, 2868, 2849, 1699, 1682,
˜
1466, 1438, 1376, 1365, 1271, 1234, 1134, 1068, 700 cm–1. 1H NMR
(500 MHz, [D6]DMSO): δ = 0.62 (s, 3 H), 0.63 (m, 1 H), 0.74 (m,
1 H), 0.76 (s, 3 H), 0.836 (d, J = 6.5 Hz, 3 H), 0.840 (d, J = 6.5 Hz,
3 H), 0.87 (d, J = 6.4 Hz, 3 H), 0.90–1.01 (m, 4 H), 1.02–1.38 (m,
15 H), 1.45–1.55 (m, 3 H), 1.61–1.66 (m, 3 H), 1.76 (m, 1 H), 1.91
(d, J = 12.3 Hz, 1 H), 2.04 (t, J = 10.0 Hz, 1 H), 3.45 (m, 1 H),
4.67 (br. s, 1 H), 11.87 (br. s, 1 H) ppm. 13C NMR and DEPT
(125 MHz, [D6]DMSO): δ = 11.86 (CH3), 12.66 (CH3), 18.50
(CH3), 20.77 (CH2), 22.40 (CH3), 22.67 (CH3), 23.17 (CH2), 23.75
(CH2), 25.30 (CH2), 27.39 (CH), 27.80 (CH2), 30.46 (CH2), 31.39
(CH2), 34.62 (CH), 34.98 (C), 35.18 (CH), 35.62 (CH2), 38.18
(CH2), 38.93 (CH2), 39.45 (CH2), 42.07 (C), 46.73 (CH), 53.39
(CH), 53.63 (CH), 55.66 (CH), 55.82 (CH), 71.40 (CH), 176.08
(C=O) ppm. MS (200 °C): m/z (%) = 432 (100) [M+], 417 (20), 414
(12), 399 (13), 278 (43), 277 (65), 260 (32), 259 (50). HRMS:
m/z [M+] calcd. for C28H48O3: 432.3603; found 432.3621.
4α-Methoxycarbonyl-5α-cholestan-3α-ol (18a) and 4α-Methoxycar-
bonyl-5α-cholestan-3β-ol (18b): Sodium borohydride (27 mg,
720 µmol) was added to a solution of the β-keto ester (17) (320 mg,
720 µmol) in methanol (50 mL)/dichloromethane (15 mL) and the
mixture was stirred for 6 h. Water was added and the precipitate
was dissolved by addition of hydrochloric acid. The phases were
separated and the aqueous phase was extracted three times with
ether. After washing with brine, the combined organic layers were
dried with magnesium sulfate and the solvent was evaporated. Puri-
fication of the residue by flash chromatography (petroleum ether/
diethyl ether, 1:1) on silica gel afforded 18a as colorless crystals,
yield: 90 mg (28%), m.p. 78 °C. IR (ATR): ν = 3514, 2929, 2866,
˜
3β-(tert-Butyldimethylsilyloxy)cholest-5-en-7-one
(21):
TBSCl
1
1718, 1442, 1382, 1197, 1170, 1112, 1060, 1005, 734, 590 cm–1. H
(471 mg, 3.12 mmol) and DMAP (381 mg, 3.12 mmol) were added
to a solution of 7-ketocholesterol (20) (1.00 g, 2.50 mmol) in
dichloromethane (10 mL). The mixture was stirred for 24 h at room
temperature and subjected directly to flash chromatography (petro-
leum ether/diethyl ether, 10:1) on silica gel to afford 21 as colorless
NMR (500 MHz, CDCl3): δ = 0.63 (s, 3 H), 0.75–0.91 (m, 2 H),
0.81 (s, 3 H), 0.84 (d, J = 6.6 Hz, 3 H), 0.85 (d, J = 6.6 Hz, 3 H),
0.88 (d, J = 6.6 Hz, 3 H), 0.96–1.03 (m, 3 H), 1.05–1.13 (m, 6 H),
1.15–1.44 (m, 7 H), 1.46–1.58 (m, 6 H), 1.64 (dq, J = 13.1, 3.1 Hz,
1 H), 1.73–1.79 (m, 2 H), 1.86 (dt, J = 3.1, 12.3 Hz, 1 H), 1.95 (dt,
J = 12.5, 3.2 Hz, 1 H), 2.46 (dd, J = 12.3, 2.0 Hz, 1 H), 3.54 (br. s,
1 H), 3.69 (s, 3 H), 4.03 (m, 1 H) ppm. 13C NMR and DEPT
(125 MHz, CDCl3): δ = 12.05 (CH3), 12.06 (CH3), 18.63 (CH3),
20.80 (CH2), 22.55 (CH3), 22.82 (CH3), 23.80 (CH2), 24.10 (CH2),
25.65 (CH2), 27.50 (CH2), 28.01 (CH), 28.20 (CH2), 31.50 (CH2),
31.62 (CH2), 35.10 (CH), 35.78 (CH), 36.11 (C), 36.14 (CH2), 39.50
(CH2), 39.91 (CH2), 41.24 (CH), 42.46 (C), 48.20 (CH), 51.54
(CH3), 54.06 (CH), 56.13 (CH), 56.35 (CH), 66.27 (CH), 177.39
(C=O) ppm. MS (180 °C): m/z (%) = 446 (100) [M+], 431 (13), 428
(16), 414 (16), 413 (45), 292 (45), 291 (42), 275 (19), 274 (28), 273
(80). HRMS: m/z [M+] calcd. for C29H50O3: 446.3760; found
446.3769.
crystals, yield: 1.13 g (88%), m.p. 212 °C. IR (ATR): ν = 2952,
˜
2935, 2859, 1665, 1626, 1471, 1375, 1253, 1191, 1093, 834, 805,
1
773 cm–1. H NMR (500 MHz, CDCl3): δ = 0.05 (s, 6 H), 0.66 (s,
3 H), 0.847 (d, J = 6.6 Hz, 3 H), 0.852 (d, J = 6.6 Hz, 3 H), 0.88
(s, 9 H), 0.91 (d, J = 6.5 Hz, 3 H), 0.99–1.37 (m, 13 H), 1.17 (s,
3 H), 1.45–1.64 (m, 5 H), 1.81 (m, 1 H), 1.89 (m, 2 H), 2.01 (dt, J
= 12.7, 3.3 Hz, 1 H), 2.22 (dd, J = 12.2, 10.9 Hz, 1 H), 2.34–2.43
(m, 3 H), 3.59 (m, 1 H), 5.65 (d, J = 1.3 Hz, 1 H) ppm. 13C NMR
and DEPT (125 MHz, CDCl3): δ = –4.70 (CH3), –4.67 (CH3), 11.94
(CH3), 17.28 (CH3), 18.14 (C), 18.86 (CH3), 21.18 (CH2), 22.54
(CH3), 22.79 (CH3), 23.79 (CH2), 25.82 (3 CH3), 26.30 (CH2), 27.98
(CH), 28.54 (CH2), 31.72 (CH2), 35.69 (CH), 36.16 (CH2), 36.39
(CH2), 38.34 (C), 38.70 (CH2), 39.45 (CH2), 42.52 (CH2), 43.05
(C), 45.39 (CH), 49.91 (CH), 49.97 (CH), 54.75 (CH), 71.31 (CH),
125.79 (CH), 165.85 (C), 202.47 (C=O) ppm. MS (150 °C): m/z (%)
18b was obtained from the more polar fraction as colorless crystals,
yield: 202 mg (63%), m.p. 171 °C. IR (ATR): ν = 3485, 2924, 2862,
˜
3700
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Eur. J. Org. Chem. 2006, 3687–3706