H. Koenig et al. / Steroids 76 (2011) 517–523
519
ı 5.32 (brd, J = 4.95 Hz, 1H, H-6), 3.86–3.39 (m, 5H, H-3␣, H-21 and
H-23), 0.998 (s, 3H, CH3-19), 0.912 [s, 9H, C(CH3)3], 0.888 [s, 9H,
C(CH3)3], 0.699 (s, 3H, CH3-18), 0.083 [s, 6H, Si(CH3)2], 0.056 [s,
6H, Si(CH3)2]. 13C NMR (C6D6): ı 141.9, 122.0, 73.4, 65.3, 61.6, 57.3,
51.8, 51.1, 44.0, 43.0, 41.5, 40.4, 38.1, 37.4, 35.2, 33.2, 32.8, 32.7,
28.5, 26.7, 25.0, 22.0, 20.1, 19.0, 18.9, 12.9, −3.74, −4.64, −4.70. MS
(FAB): m/z (%) 591 ([M+H]+, 70), 327 (100), 159 (58), 133 (64). Anal-
ysis calcd for: C35H67O3Si2: C, 71.12; H, 11.25. Found: C, 71.20; H,
11.37.
(4), 75 (14), 17 (21). HRMS calcd for C35H61O4Si2: 601.4108; found
601.4094.
2.8.
(20S)-3ˇ,21-Bis(t-butyldimethylsilyloxy)-24-norchol-5-en-23-al
(10)
The oxidation of compound 7 (65 mg, 0.11 mmol) was carried
out as for alcohol 6 (vide supra) to give a crude product (52 mg),
which was chromatographed on a silica gel column (1.5 g) with
benzene as the eluent. Compound 10 (35.5 mg, 54%) was obtained
as a white solid; mp 154–157 ◦C (benzene). IR: ꢀmax 3031–282,
7. White solid, mp 148–149 ◦C (acetone). IR (KBr): ꢀmax 3495,
1254, 1097, 1029, 864, 839, 776 cm−1 1H NMR (CDCl3): ı 5.31 (brd,
.
J = 5.21 Hz, 1H, H-6), 3.77–3.60 (m, 3H) and 3.51–3.42 (m, 2H), (3␣-
H, H-21, and H-23), 0.996 (s, 3H, H-19), 0.907 [s, 9H, C(CH3)3], 0.888
[s, 9H, C(CH3)3], 0.703 (s, 3H, H-18), 0.077 [s, 6H, Si(CH3)2], 0.057
[s, 6H, Si(CH3)2]. 13C NMR: ı 142.0, 121.9, 73.4, 65.8, 61.1, 57.2,
51.3, 50.9, 44.0, 43.0, 41.5, 40.5, 38.1, 37.3, 35.1, 33.1, 32.7, 28.4,
26.6, 26.5, 24.9, 21.8, 20.0, 18.9, 18.8, 12.6, −3.85, −4.88, −4.92.
MS (FAB): m/z (%) 591 ([M+H]+, 46), 327 (88), 145 (82), 133 (100).
Analysis calcd for C35H67O3Si2: C, 71.12; H, 11.25. Found: C, 70.93;
H, 11.14.
2733, 1722 (C O), 1360, 1259, 1196, 950, 959, 938, 891, 779 cm−1
.
1H NMR (CDCl3): ı 9.77 (dd, J1 = 1 Hz, J2 = 3.4 Hz, 1H, H-23), 5.32
(brd, J = 5.2 Hz, 1H, H-6), 3.68 (dd, J1 = 3.6 Hz, J2 = 9.9 Hz, 1H, HA-
21), 3.48 (m, 1H, H-3␣) 3.42 (dd, J1 = 7.6 Hz, J2 = 9.9 Hz, 1H, HB-21),
0.996 (s, 3H, CH3-19), 0.889 [s, 9H, C(CH3)3], 0.870 [s, 9H, C(CH3)3],
0.727 (s, 3H, CH3-18), 0.058, 0.015 [s, 12H, Si(CH3)2]. MS (EI):
m/z (%) 531 (100) (M+−t-Bu), 399 (85), 307 (44), 253 (30). HRMS
calcd for C31H55O3Si2: 531.3690; found 531.3671. Analysis calcd
for C35H64O3Si2: C, 71.12; H, 11.25. Found: C, 71.20; H, 11.37.
2.6.
2.9. Ethyl (20S)-3ˇ,21-bis(t-butyldimethylsilyloxy)-25-
homochola-5,23-dien-25-oate
(11)
(20R)-3ˇ,21-Bis(t-butyldimethylsilyloxy)-24-norchol-5-en-23-al
(8)
To a solution of DMSO (235 l, 3.30 mmol) in methylene chlo-
ride (5 ml) stirred under argon at −78 ◦C oxalyl chloride (170 l,
0.2 mmol) was added and the mixture was stirred for 5 min. A
solution of compound 6 (147 mg, 0.25 mmol) in CH2Cl2 (5 ml) was
added dropwise over 10 min and the resulting solution was stirred
at −78 ◦C for 0.5 h. Triethylamine (1.35 ml, 9.7 mmol) was added
and the stirring was continued for another 5 min. The mixture was
warmed to room temperature, NaHCO3 (10%, 2.5 ml) was added
followed by ether. The organic layer was washed with water, dried
(MgSO4) and evaporated under reduced pressure to give a crude
product (178.5 mg), which was chromatographed on silica gel col-
umn (5 g) with benzene as the eluent. Compound 8 (107.5 mg, 73%)
was obtained as an oil. 1H NMR (CDCl3): ı 9.75 (t, J = 2.4 Hz, 1H, H-
23), 5.31 (brd, J = 5.4 Hz, 1H, H-6), 3.84 (dd, J1 = 4.2 Hz, J2 = 9.9 Hz,
1H, H-21), 3.48 (m, 1H, H-3␣), 3.41 (dd, J1 = 8.4 Hz, J2 = 9.9 Hz,
1H, H-21), 1.00 (s, 3H, CH3-19), 0.889 [s, 9H, C(CH3)3], 0.878
[s, 9H, C(CH3)3], 0.732 [s, 3H, CH3-18], 0.058 [s, 6H, SiC(CH3)2].
MS (EI): m/z (%) 531 ([M−t-Bu]+, 100), 399 (54), 307 (26), 253
(14), 145 (20). HRMS calcd for C31H55O3Si2: 531.3690; found
531.3698.
To
a solution of aldehyde 10 (29.2 mg, 0.0496 mmol) in
anhydrous benzene (1 ml) Ph3P = CHCOOEt (21.3 mg, 0.061 mmol,
1.2 eq) was added and the mixture was refluxed under argon for
8 h. An additional portion of the ylide (42.5 mg, 2.4 eq) was added
and refluxing continued for 5 h. The solvent was evaporated under
reduced pressure and the residue was chromatographed on a silica
gel column (3 g) with hexane and a mixture of hexane–benzene
(1:1) as the eluent to give ester 11 (27.8 mg, 85%) as an oil. IR:
ꢀmax 3394, 2953, 2932, 2857, 1721, 1673, 1655, 1471, 1463, 1386,
1257, 1095, 1005, 939, 836, 775, 758, 666 cm−1 1H NMR: ı 6.91
.
(dt, J23–24 = 15.5, J23–22 = 7.4 Hz, 1H, H-23), 5.82 (d, J24–23 = 15.7 Hz,
1H, H-24), 5.31 (brd, J = 4.9 Hz, 1H, H-6), 4.17 (q, J = 7.1 Hz, 2H,
OCH2CH3), 3.55 (dd, J = 3.0 Hz, 1H, H-21), 3.38–3.50 (m, 2H, H-3␣,
H-21), 1.28 (t, J = 7.1 Hz, 3H, OCH2CH3), 0.99 (s, 3H, CH3-19), 0.88
(s, 9H, t-BuSi), 0.89 (s, 9H, t-BuSi), 0.70 (s, 3H, CH3-18), 0.06 [s, 6H,
(CH3)2Si], 0.01[s, 6H, (CH3)2Si]. MS (EI): m/z (%) 601 (100) (M+−t-
Bu), 469 (10), 75 (12). HRMS calcd for C35H61O4Si2: 601.4108; found
601.4107.
2.10. (20)-3ˇ-(t-Butyldimethylsilyloxy)-21,23-epoxy-24-
norchol-5-en-23-ol
(12)
2.7. Ethyl (20R)-3ˇ,21-bis(t-butyldimethylsilyloxy)-25-
homochola-5,23-dien-25-oate
(9)
To a solution of lactone 2 (167 mg, 0.35 mmol) in anhydrous
toluene (5 ml) stirred at −78 ◦C under argon a solution of DIBALH
(1 M, 2.2 ml) in hexanes was added and stirring was continued for
1 h. Acetic acid (2 ml) was added and the mixture was stirred at
room temp. for 0.5 h. Extraction with ether was followed by usual
workup to give a crude product (160.9 mg) as a white solid, which
was chromatographed on a silica gel column with benzene–AcOEt
(20:1) as the eluent. The combined pure fractions gave lactol 12
(141.2 mg, 84%), mp 178–183 ◦C (benzene). IR (KBr): ꢀmax 3600,
To a solution of aldehyde 8 (55.5 mg, 0.093 mmol) in anhydrous
benzene (3 ml) (carbethoxymethylene)triphenylphosphorane
(Ph3P = CHCOOEt) (120.0 mg, 0.33 mmol, 10.8 eq) was added and
the mixture was refluxed under argon for 4.5 h. The solvent
was evaporated under reduced pressure and the residue was
chromatographed on a silica gel column (6 g) with hexane as
the eluent to give ester 9 (47.1 mg, 76%) as an oil. IR: ꢀmax 2952,
2931, 2902, 2856, 1722, 1650, 1471, 1462, 1382, 1368, 1309, 1256,
3410, 1255, 1094, 1069, 888, 869, 837 cm−1 1H NMR (CDCl3): ı
.
1204, 1165, 1093, 1047, 1005, 959, 939, 836, 774,666 cm−1 1H
;
5.56–5.42 (m, 1H, H-23), 5.32 (brd, J = 5.5 Hz, 1H, H-6), 4.24–3.86
(m, 1H, H-21), 3.62–3.38 (m, 1H, H-21), 3.48 (m, 1H, H-3␣), 1.005
and 0.998, (2s, 3H, CH3-19), 0.89 [s, 9H, SiC(CH3)3], 0.71, 0.69, 0.67,
and 0.66 (2s, 3H, CH3-18), 0.06 [s, 6H, Si(CH3)2]. MS (EI): m/z (%)
474 (1) (M+), 417 (100) (M+−t-Bu), 399 (69), 331 (12), 255 (15),
171 (11), 159 (23), 145 (23), 75 (94). HRMS calcd for C28H47O3Si
(M+−CH3): 459.3294; found 459.3287.
NMR: ı 6.98 (dt, J23–24 = 15.4, J23–22 = 6.7 Hz, 1H, H-23), 5.85 (d,
J24–23 = 15.7 Hz, 1H, H-24), 5.31 (brd, J = 4.9 Hz, 1H, H-6), 4.18 (q,
J = 7.1 Hz, 2H, OCH2CH3), 3.67 (dd, J = 4.1, J = 3.6 Hz, 1H, H-21),
3.44–3.53 (m, 2H, H-3␣, H-21), 1.28 (t, J = 7.1 Hz, 3H, OCH2CH3),
0.99 (s, 3H, CH3-19), 0.88 (s, 9H, t-BuSi), 0.89 (s, 9H, t-BuSi), 0.68
(s, 3H, CH3-18), 0.06 [s, 6H, (CH3)2Si], 0.03 [s, 6H, (CH3)2Si]. MS
(EI): m/z (%) 601 ([M−t-Bu]+, 100), 469 (25), 272 (5), 249 (2), 159