9742
B. Jiang et al. / Tetrahedron 64 (2008) 9738–9744
54.4, 52.0, 47.2, 41.7, 37.4, 36.4, 34.7, 33.2, 32.9, 31.7, 31.4, 31.1, 25.9,
21.0, 20.9, 18.7, 18.3, 18.1, 16.2, 13.5, ꢁ4.1, ꢁ4.6, ꢁ4.7; EIMS: 561
(Mþꢁt-Bu), 501 (Mþꢁ2t-Bu); HRMS calcd for C32H57O4Siþ2 :
561.3795; found: 561.3796.
31.7, 30.2, 25.9, 25.8, 21.0, 18.3, 18.0, 17.2, 14.6, 13.4, ꢁ4.1, ꢁ4.6, ꢁ4.7,
ꢁ4.8; ESI-MS: 659.2 (MþNaþ); HRMS calcd for C36H68O5Si2Naþ:
659.4504; found: 659.4498.
4.1.10. 22-Acetoxy-3b,6a-bis[(tert-butyldimethylsilyl)oxy]-15b-
4.1.7. 22-Acetoxy-3
b,6
a
-bis[(tert-butyldimethylsilyl)oxy]-5
a-
methoxymethyl-5 -23,24-bisnorcholane (16)
a
23,24-bisnorchol-16-ene-15-one (13)
To a solution of 15 (50 mg, 0.08 mmol) and N,N-diisopropyl-
A mixture of 12 (30 mg, 0.048 mmol), N-hydroxy phthalimide
(32 mg, 0.20 mmol) and Na2Cr2O7$2H2O (30 mg, 0.10 mmol) in
freshly distilled acetone (1.5 mL) was stirred at 40 ꢀC for 3 h. Ad-
ditional N-hydroxy phthalimide (32 mg, 0.20 mmol) and
Na2Cr2O7$2H2O (30 mg, 0.10 mmol) were added and the reaction
mixture was allowed to keep overnight at the same temperature.
Saturated sodium sulfite (2 mL) was added to remove the oxidant.
After the reaction mixture was filtered, the filtrate was extracted
with EtOAc (15 mLꢂ2). The combined organic extracts were
washed with brine (20 mLꢂ2), dried over anhydrous Na2SO4, fil-
tered and concentrated. The crude product was purified by flash
ethylamine (0.15 mL, 0.86 mmol) in freshly distilled CH2Cl2 (7 mL),
MOMCl (45 mL) was added slowly by syringe. The solution was
allowed to reflux overnight. After being cooled to room tempera-
ture, the reaction was quenched by water. The aqueous layer was
extracted with CH2Cl2 (10 mLꢂ2). The combined organic extracts
were washed with 0.1 M HCl (5 mLꢂ2), saturated NaHCO3
(8 mLꢂ2) and brine (10 mLꢂ3), dried over anhydrous Na2SO4, fil-
tered and concentrated in vacuo. Flash chromatography (hexane/
EtOAc, 20:1) afforded 16 (50 mg, 94%) as a colorless oil. [
a]
20 16.2 (c
D
4.2, CHCl3); IR (KBr): 2856, 1743, 1249, 1083, 836, 774 cmꢁ1
;
1H
NMR (300 MHz, CDCl3): 4.61, 4.53 (AB, 2H, JAB¼6.3 Hz), 4.04 (dd,
1H, J¼10.8, 3.3 Hz), 3.87 (t, 1H, J¼6.0 Hz), 3.77 (dd, 1H, J¼10.5,
7.5 Hz), 3.51–3.47 (m, 1H), 3.42–3.38 (m, 1H), 3.34 (s, 3H), 2.31–2.27
(m,1H), 2.03 (s, 3H),1.00 (d, 3H, J¼6.6 Hz), 0.89 (s, 3H), 0.86 (s,18H),
0.82 (s, 3H), 0.02 (s, 6H), 0.01 (s, 3H), ꢁ0.004 (s, 3H); 13C NMR
chromatography (hexane/EtOAc, 8:1) afforded 13 (15 mg, 74%,
20
10 mg of 12 was recovered) as a light yellow oil. [
a
]
22.7 (c 1.60,
D
CHCl3); IR (KBr): 2930, 1743, 1712, 1471, 1097, 836, 775 cmꢁ1
;
1H
NMR (300 MHz, CDCl3): 5.66 (s, 1H), 4.15–4.04 (m, 2H), 3.53–3.49
d
(m, 1H), 3.46–3.42 (m, 1H), 2.97–2.93 (m, 1H), 2.79 (q, 1H, J¼7.2 Hz),
(75 MHz, CDCl3): d 171.3, 97.5, 78.0, 72.2, 70.1, 69.3, 60.1, 55.9, 54.1,
0.99 (s, 3H), 0.89 (s, 9H), 0.87 (s, 9H), 0.85 (s, 3H), 0.06 (s, 6H), 0.04
52.9, 51.8, 42.6, 41.0, 40.7, 38.4, 37.6, 36.3, 35.4, 33.1, 31.7, 30.4,
25.89, 25.88, 20.94, 20.92, 18.3, 18.1, 17.2, 14.2, 13.5, ꢁ4.2, ꢁ4.66,
ꢁ4.75, ꢁ4.8; ESI-MS: 703.3 (MþNaþ); HRMS calcd for
(s, 6H); 13C NMR (75 MHz, CDCl3):
d 206.7, 183.3, 170.8, 125.6, 72.0,
69.7, 67.0, 63.3, 54.3, 51.9, 46.9, 39.8, 37.3, 36.3, 33.0, 32.3, 32.2, 31.6,
30.9, 25.92, 25.88, 23.4, 20.8, 18.3, 18.1, 17.8, 13.5, ꢁ4.0, ꢁ4.68.
ꢁ4.75, ꢁ4.8; ESI-MS: 575 (Mþꢁt-Bu), 515 (Mþꢁ4Me); HRMS calcd
for C32H55O5Siþ2 : 575.3588; found: 575.3583.
C
38H72O6Si2Naþ: 703.4752; found: 703.4760.
4.1.11. 3
b,6a-Bis[(tert-butyldimethylsilyl)oxy]-15b-methoxy-
methyl-5
a
-23,24-bisnorcholan-22-ol (17)
4.1.8. 22-Acetoxy-3
23,24-bisnorcholan-15-one (14)
b
,6
a
-bis[(tert-butyldimethylsilyl)oxy]-5
a
-
Compound 16 (84 mg, 0.12 mmol) in MeOH (13 mL) was treated
with KOH solution (4.8 mL, 10 wt % in MeOH) under ice-salt bath.
The reaction mixture was warmed to room temperature and stirred
for 1 h. The solution was diluted with EtOAc, acidified with 0.3 M
HCl (3 mLꢂ2), washed with saturated NaHCO3 (5 mLꢂ2) and brine
(10 mLꢂ3), dried over anhydrous Na2SO4, filtered and concentrated
in vacuo. Flash chromatography (hexane/EtOAc, 10:1 to 4:1) affor-
Ketone 13 (64 mg, 0.1 mmol) in EtOAc (2.5 mL) was hydroge-
nated over 10 wt % Pd/C (8 mg) for 2 days. After the reaction mix-
ture was diluted by EtOAc (10 mL), the catalyst was removed by
filtration through Celite. The filtrate was concentrated. Flash
chromatography (hexane/EtOAc, 8:1) afforded 14 (64 mg, 99%) as
a white solid. Mp 72–73 ꢀC; [
a
]
20 27.9 (c 1.00, CHCl3); IR (KBr): 2955,
ded 17 (78 mg, 99%) as a white solid. Mp 123–124 ꢀC; [
a]
20 12.5 (c
D
D
1743, 1251, 1082, 836, 774 cmꢁ1
;
1H NMR (300 MHz, CDCl3): 4.01
2.85, CHCl3); IR (KBr): 2932, 1251, 1093, 836, 776 cmꢁ1
;
1H NMR
(dd, 1H, J¼10.8, 3.3 Hz), 3.81 (dd, 1H, J¼10.8, 6.6 Hz), 3.53–3.46 (m,
1H), 3.39 (dt, 1H, J¼9.6, 4.2 Hz), 2.92–2.88 (m, 1H), 2.42 (dd, 1H,
J¼18.3, 8.4 Hz), 2.10–2.08 (m, 2H), 2.05 (s, 3H), 1.08 (d, 3H,
J¼6.6 Hz), 0.873 (s, 9H), 0.866 (s, 9H), 0.79 (s, 3H), 0.74 (s, 3H), 0.07
(300 MHz, CDCl3): 4.62, 4.54 (AB, 2H, JAB¼6.3 Hz), 3.87 (t, 1H,
J¼6.0 Hz), 3.64–3.61 (m, 1H), 3.53–3.46 (m, 1H), 3.43–3.39 (m, 2H),
3.35 (s, 3H), 2.36–2.26 (m, 1H), 1.03 (d, 3H, J¼5.7 Hz), 0.90 (s, 3H),
0.87 (s, 18H), 0.82 (s, 3H), 0.03 (s, 6H), 0.01 (s, 3H), ꢁ0.001 (s, 3H);
(s, 3H), 0.04 (s, 3H), 0.03 (s, 6H); 13C NMR (75 MHz, CDCl3):
d
214.44,
13C NMR (75 MHz, CDCl3):
d 97.6, 78.3, 72.3, 70.1, 67.7, 60.2, 55.9,
171.2, 72.1, 69.7, 68.9, 65.0, 53.3, 51.7, 48.1, 42.2, 41.1, 40.1, 39.5, 37.5,
36.2, 35.3, 33.0, 31.6, 30.5, 25.9, 20.9, 20.6, 18.3, 18.1, 17.5, 13.4, 12.9,
ꢁ4.1, ꢁ4.67, ꢁ4.72, ꢁ4.9; ESI-MS: 635.5 (MþHþ); HRMS calcd for
54.2, 52.6, 51.9, 42.5, 41.0, 40.7, 38.5, 38.4, 37.6, 36.3, 35.4, 33.1, 31.7,
30.4, 25.9, 20.9, 18.3, 18.1, 16.7, 14.2, 13.5, ꢁ4.2, ꢁ4.65, ꢁ4.75, ꢁ4.8;
ESI-MS: 661.2 (MþNaþ); HRMS calcd for C36H70O5Si2Naþ:
661.4663; found: 661.4654.
C
36H66O5Si2Naþ: 657.4359; found: 657.4341.
4.1.9. 22-Acetoxy-3
b,6
a
-bis[(tert-butyldimethylsilyl)oxy]-5
a-
4.1.12. 3
b a-Bis[(tert-butyldimethylsilyl)oxy]-15b-methoxy-
,6
23,24-bisnorcholan-15
b
-ol (15)
methyl-5a-23,24-bisnorcholan-22-al (6)
To a solution of 14 (19 mg, 0.03 mmol) in THF (3 mL) and MeOH
(1 mL) was added NaBH4 (6 mg, 0.15 mmol) at 0 ꢀC. The mixture
was allowed to stir at the same temperature for 30 min and
quenched by water. The aqueous layer was extracted with CH2Cl2
(5 mLꢂ3). The combined organic extracts were washed with brine
(10 mLꢂ2), dried over anhydrous Na2SO4, filtered and concen-
Preparation of pyridine-buffered Dess–Martin periodinane stock
solution: to a suspension of Dess–Martin periodinane (52 mg,
0.12 mmol) in freshly distilled CH2Cl2 (2 mL) under argon, pyridine
(60 m
L, 0.5 mmol) was added at 0 ꢀC. The clear solution was used
within 20 min.
To a solution of alcohol 17 (20 mg, 0.03 mmol) in freshly distilled
CH2Cl2 (1.5 mL) under argon, the freshly prepared pyridine-buff-
ered Dess–Martin periodinane (2 mL, 0.12 mmol) was added by
syringe under ice bath. The solution was warmed to room tem-
perature and stirred for 1 h. The reaction was quenched by 1:1
saturated NaHCO3/sodium bisulfite (5 mL) and stirred for 15 min.
The aqueous layer was extracted with CH2Cl2 (10 mLꢂ2). The
combined organic extracts were washed with saturated NaHCO3
(5 mLꢂ2) and brine (10 mLꢂ3), dried over anhydrous Na2SO4, fil-
tered and concentrated in vacuo. Flash chromatography (hexane/
trated. Flash chromatography (hexane/EtOAc, 9:1) afforded 15
20
(18 mg, 94%) as a white solid. Mp 114–115 ꢀC; [
a]
4.9 (c 0.9,
D
CHCl3); IR (KBr): 2930, 1730, 1259, 1089, 836, 773 cmꢁ1 1H NMR
;
(300 MHz, CDCl3): 4.22 (t, 1H, J¼6.0 Hz), 4.05 (dd, 1H, J¼10.5,
3.0 Hz), 3.78 (dd, 1H, J¼10.5, 7.2 Hz), 3.52–3.49 (m, 1H),3.42 (dt, 1H,
J¼10.2, 4.5 Hz), 2.39–2.34 (m, 1H), 2.14–2.08 (m, 2H), 2.05 (s, 3H),
1.00 (d, 3H, J¼6.3 Hz), 0.95 (s, 3H), 0.87 (s, 18H), 0.83 (s, 3H), 0.04 (s,
6H), 0.02 (s, 6H); 13C NMR (75 MHz, CDCl3):
d 171.4, 76.6, 72.2, 70.2,
70.0, 69.3, 60.2, 54.1, 53.0, 51.9, 42.4, 41.0, 40.7, 37.6, 36.3, 35.4, 33.1,