1180
Vol. 51, No. 10
saturated aqueous NaHCO3 (5 mlϫ2), and brine (5 mlϫ2). The organic layer
was dried over anhydrous MgSO4 and concentrated in vacuo. The residue
was purified on a silica gel column (hexane : EtOAcϭ5 : 1) to afford 24-O-t-
butyldimethylsilyloxy compound 4e as a white solid (292 mg, 78% yield):
mp 93.5—95 °C; [a]D26 Ϫ34.4° (cϭ1.00, CHCl3); IR (KBr) 3470, 2937,
1H, C-3H), 4.59—4.62 (m, 1H, C-24H), 4.74 (s, 1H), 4.84 (s, 1H), 5.37 (d,
1H, olefin-H, Jϭ5.2 Hz); 13C-NMR d: Ϫ5.0, Ϫ4.7, Ϫ3.8, 11.8, 17.3, 18.0,
18.8, 19.3, 21.0, 21.4, 25.9, 26.0 (ϫ3), 27.8, 28.0, 31.6, 31.9, 32.5, 35.6,
36.0, 36.6, 37.0, 38.1, 39.7, 42.3, 50.0, 55.9, 56.6, 74.0, 110.3, 122.6, 139.6,
148.0,170.4.
1
1733, 1471 cmϪ1; H-NMR d: 0.09 (s, 3H), 0.10 (s, 3H), 0.68 (s, 3H), 0.92
(24R)-3b-Acetoxy-24-benzoyloxycholest-5-ene (6) A solution of D25
compound 5a (3.70 g, 6.77 mmol) in EtOAc (100 ml) was stirred at room
temperature in the presence of 10% Pd–C (370 mg) under an atmospheric
pressure of hydrogen. After 3 h, the reaction mixture was filtered, and the fil-
trate was concentrated in vacuo. The resulting syrup was purified by silica
gel column chromatography (hexane : EtOAcϭ8 : 1) to afford the saturated
compound 6 as a white powder (2.34 g, 63% yield): mp 114—121 °C; [a]D26
Ϫ30.0° (cϭ1.02, CHCl3); IR (KBr) 3444, 3068, 2934, 2872, 1735, 1708,
(s, 12H), 1.02 (s, 3H), 1.13 (s, 3H), 1.15 (s, 3H), 2.03 (s, 3H, –C(O)CH3),
0.64—2.04 (m, 24H), 2.31—2.33 (m, 2H), 3.35—3.44 (m, 1H, C-3H),
4.56—4.64 (m, 1H, C-24H), 5.37 (d, 1H, olefin-H, Jϭ4.8 Hz); 13C-NMR d:
Ϫ4.3 (ϫ2), Ϫ3.6, 11.8, 18.3, 18.6, 19.3, 21.0, 21.4, 24.2, 24.3, 26.1 (ϫ3),
26.9, 27.8, 28.3, 30.1, 31.9 , 33.1, 36.3, 36.6, 37.0, 38.1, 39.7, 42.3, 50.0,
56.1, 56.7, 73.2, 74.0, 80.3, 122.6, 139.7, 170.5.
(24R)-3b-Acetoxy-24-benzoyloxycholesta-5,22-diene (5a) To a solu-
tion of 24-O-benzoate 4a (7.80 g, 13.8 mmol) in pyridine (130 ml) POCl3
(5.20 ml, 55.2 mmol) was added at 0 °C, and the mixture was stirred for 12 h
at room temperature. EtOAc (50 ml) and water (20 ml) were added to the re-
action mixture, and the solution was stirred for 30 min at room temperature,
and then the organic layer was washed with 1 N hydrochloric acid (15 mlϫ2),
saturated aqueous NaHCO3 (15 mlϫ2), and brine (15 mlϫ2). The organic
layer was dried over anhydrous MgSO4 and concentrated in vacuo to give a
white crystalline solid, which was recrystallized from hexane–EtOAc to af-
ford D25 compound 5a as a white powder (7.55 g, 86% yield). mp 137—
143 °C; [a]D26 Ϫ53.0° (cϭ1.00, CHCl3); IR (KBr) 3434, 2936, 2871, 1733,
1601, 1584, 1467, 1452 cmϪ1 1H-NMR d: 0.66 (s, 3H), 0.92 (d, 3H,
;
Jϭ6.8 Hz), 0.96 (d, 3H, Jϭ6.8 Hz), 0.98 (d, 3H, Jϭ6.8 Hz ), 1.01 (s, 3H),
2.02 (s, 3H, –C(O)CH3), 0.93—2.04 (m, 24H), 2.30—2.32 (m, 2H), 4.58—
4.61 (m, 1H, C-3H), 4.95—4.99 (m, 1H, C-24H), 5.36 (d, 1H, olefin-H,
Jϭ4.4 Hz), 7.44 (t, 2H, Ar-H, Jϭ7.8 Hz), 7.55 (t, 1H, Ar-H, Jϭ7.3 Hz), 8.05
(d, 2H, Ar-H, Jϭ8.3 Hz); 13C-NMR d: 11.8, 17.7, 18.6, 18.7, 19.3, 20.9,
21.4, 24.2, 27.5, 27.7, 28.0, 31.5, 31.6, 31.8, 35.4, 36.6, 37.0, 38.1, 39.7,
42.3, 50.0, 55.7, 56.6, 74.0, 77.2, 79.4, 122.6, 128.3 (ϫ2), 129.5 (ϫ2),
130.9, 132.6, 139.6, 166.4, 170.5. Anal. Calcd for C36H52O4: C, 78.79; H,
9.55. Found: C, 78.60; H, 9.62.
1708, 1654, 1602, 1453 cmϪ1 1H-NMR d: 0.66 (s, 3H), 0.95 (d, 3H,
;
(24R)-3b-Acetoxy-24-benzoyloxycholest-5-en-7-one (7) The hydro-
genated product 6 (3.00 g, 5.47 mmol) and N-hydroxylphthalamide (893 mg,
5.58 mmol) were dissolved in EtOAc–acetone (300 ml, 1 : 1 v/v), and ben-
zoyl peroxide (300 mg) was added to the reaction solution at 50—60 °C. Air
was bubbled into the reaction solution with stirring for 48 h at 50—60 °C,
and then the reaction mixture was concentrated in vacuo. Carbon tetrachlo-
ride (200 ml) was added to the residual syrup, the suspension was stirred for
10 min at room temperature, and then the insoluble material was filtered off.
The filtrate was concentrated in vacuo, and a solution of the residue in pyri-
dine (50 ml) was treated with acetic anhydride (5 ml) for 12 h at room tem-
perature. The reaction mixture was concentrated in vacuo to give a syrup,
which was purified on a silica gel column (hexane : EtOAcϭ4 : 1) and then
the crude crystals were recrystallized from hexane–EtOAc to afford 7-oxo
compound 7 as a white powder (1.96 g, 64% yield): mp 137—140 °C; [a]D26
Ϫ86.2° (cϭ1.04, CHCl3); IR (KBr) 3456, 2960, 2866, 1736, 1709, 1665,
Jϭ6.3 Hz), 1.00 (s, 3H), 1.79 (s, 3H), 2.01 (s, 3H, –C(O)CH3), 0.90—2.02
(m, 23H), 2.30—2.33 (m, 2H), 4.58—4.60 (m, 1H, C-3H), 4.90 (s, 1H, one
proton of CϭCH2), 5.02 (s, 1H, another proton of CϭCH2), 5.35—5.39 (m,
2H, olefin-H and C-24H), 7.42 (t, 2H, Ar-H, Jϭ7.8 Hz), 7.53 (t, 1H, Ar-H,
Jϭ6.8 Hz), 8.05 (d, 2H, Ar-H, Jϭ8.3 Hz); 13C-NMR d: 11.8, 18.3, 18.7,
19.3, 21.0, 21.4, 24.2, 27.8, 28.1, 29.2, 31.4, 31.9, 35.4, 36.6, 37.0, 38.1,
39.7, 42.3, 50.0, 55.7, 56.7, 74.0, 77.2, 78.2, 112.6, 122.6, 128.3 (ϫ2), 129.5
(ϫ2), 130.7, 132.8, 139.6, 143, 4, 165.8, 170.5. Anal. Calcd for C36H50O4:
C, 79.08; H, 9.22. Found: C, 79.05; H, 9.28.
(24R)-3b-Acetoxy-24-pivaloyloxycholesta-5,22-diene (5b) The pival-
oyl compound 5b (248 mg, 92%) was obtained from 4b (278 mg, 513 mmol)
by a similar procedure to that for the benzoyl analogue 5a. mp 139—146 °C;
[a]D26 Ϫ40.1° (cϭ1.00, CHCl3); IR (KBr) 2939, 2906, 2871, 2821, 1731,
1653, 1458 cmϪ1; 1H-NMR d: 0.67 (s, 3H), 0.93 (d, 3H, Jϭ6.4 Hz), 1.02 (s,
3H), 1.21 (s, 9H), 1.71 (s, 3H), 2.03 (s, 3H, –C(O)CH3), 0.92—2.04 (m,
23H), 2.31—2.33 (m, 2H), 4.59—4.61 (m, 1H, C-3H), 4.85 (s, 1H), 4.92 (s,
1H), 5.06—5.10 (m, 1H, C-24H), 5.37 (d, 1H, olefin-H, Jϭ4.8 Hz); 13C-
NMR d: 11.8, 18.3, 18.7, 18.9, 19.3, 21.0, 21.4, 24.2, 27.1, 27.2 (ϫ3), 27.8,
28.1, 29.1, 31.3, 31.9, 35.2, 36.6, 37.0, 38.1, 38.8, 39.7, 42.3, 50.0, 55.8,
56.7, 74.0, 111.8, 122.6, 139.7, 143.8, 170.5, 177.6.
1632, 1605, 1587, 1454 cmϪ1 1H-NMR d: 0.66 (s, 3H), 0.93 (d, 3H,
;
Jϭ6.3 Hz), 0.97 (d, 3H, Jϭ6.3 Hz), 0.97 (d, 3H, Jϭ6.3 Hz ), 1.20 (s, 3H),
2.05 (s, 3H, –C(O)CH3), 0.93—2.56 (m, 24H), 4.68—4.74 (m, 1H, C-3H),
4.95—4.99 (m, 1H, C-24H), 5.69 (d, 1H, olefin-H, Jϭ1.5 Hz), 7.44 (t, 2H,
Ar-H, Jϭ7.3 Hz), 7.55 (t, 1H, Ar-H, Jϭ7.3 Hz), 8.05 (d, 2H, Ar-H,
Jϭ7.3 Hz); 13C-NMR d: 11.9, 17.2, 17.8, 18.7, 18.8, 21.1, 21.2, 26.2, 27.3,
28.3, 31.4, 31.6, 35.2, 36.0, 37.7, 38.3, 38.6, 43.1, 45.4, 49.8, 49.9, 54.4,
72.2, 77.2, 79.3, 126.7, 128.3 (ϫ2), 129.5 (ϫ2), 130.8, 132.7, 163.8, 166.4,
170.2, 201.8. Anal. Calcd for C36H50O5·0.3H2O: C, 76.10; H, 8.97. Found:
C, 76.14; H, 9.04.
(24R)-3b-Acetoxy-24-tetrahydropyranyloxycholesta-5,22-diene
(5c)
The tetrahydropyranyl compound 5c (72 mg, 48%) was obtained from 4c
(156 mg, 288 mmol) by a similar procedure to that for the benzoyl analogue
5a. mp 131—135 °C; [a]D26 Ϫ60.7° (cϭ1.00, CHCl3); IR (KBr) 2940, 1732,
1
1652, 1441 cmϪ1; H-NMR d 0.68 (s, 3H), 0.92 (d, 3H, Jϭ6.4 Hz), 1.02 (s,
(24R)-3b-Acetoxy-24-benzoyloxy-7b-hydroxycholestane (8) and (24R)-
3b-Acetoxy-24-benzoyloxycholestan-7-one (9) A solution of 7-oxo com-
pound 7 (2.52 g, 4.59 mmol) in EtOAc (200 ml) was stirred at room tempera-
ture in the presence of platinum oxide (126 mg) under an atmospheric pres-
sure of hydrogen. After 3 h, the reaction mixture was filtered, and the filtrate
was concentrated in vacuo to give a syrup, which was purified by silica gel
column chromatography (hexane : EtOAcϭ3 : 1) to yield 5a-7-hydroxy com-
pound 8 as a colorless syrup (585 mg, 23% yield) and 5a-7-oxo compound
9 as a colorless syrup (1.66 g, 66% yield). Compound 8: [a]D26 Ϫ28.5°
3H), 1.09 (d, 3H, Jϭ6.8 Hz), 1.73 (s, 3H), 2.03 (s, 3H, –C(O)CH3), 0.91—
2.03 (m, 25H), 2.31—2.33 (m, 2H), 3.28—3.30 (m, 1H), 3.40—3.45 (m,
1H, C-3H), 3.82—3.92 (m, 1H), 4.55—4.65 (m, 1H, C-24H), 4.66—4.68
(m, 2H), 4.82 (s, 1H), 4.92 (s, 1H), 5.37 (d, 1H, olefin-H, Jϭ4.8 Hz); 13C-
NMR d: 11.8, 17.4, 17.8, 18.7, 19.3, 19.6, 21.0, 21.4, 24.2, 25.5, 27.7, 28.1,
30.9, 31.0, 31.2, 31.8, 35.6, 36.5, 36.9, 38.1, 39.6, 42.2, 49.9, 55.7, 56.6,
62.6, 73.9, 81.3, 97.9, 111.5, 122.6, 139.6, 145.9, 170.5.
(24R)-3b-Acetoxy-24-methoxymethyloxycholesta-5,22-diene (5d)
The methoxymethyl compound 5d (86 mg, 66%) was obtained from 4d
(135 mg, 269 mmol) by a similar procedure to that for the benzoyl analogue
5a. mp 97—103 °C; [a]D26 ϩ4.7° (cϭ1.00, CHCl3); IR (KBr) 2939, 2360,
1
(cϭ0.96, CHCl3); IR 3417, 2950, 2873, 1737, 1713, 1603, 1451 cmϪ1; H-
NMR d: 0.66 (s, 3H), 0.84 (s, 3H), 0.92 (d, 3H, Jϭ6.4 Hz), 0.96 (d, 3H,
Jϭ6.3 Hz), 0.97 (d, 3H, Jϭ6.8 Hz ), 2.02 (s, 3H, –C(O)CH3), 0.91—2.35
(m, 28H), 3.35 (m, 1H, C-7H), 4.67 (m, 1H, C-3H), 4.96 (m, 1H, C-24H),
7.44 (t, 2H, Ar-H, Jϭ7.8 Hz), 7.55 (t, 1H, Ar-H, Jϭ6.8 Hz), 8.05 (d, 2H, Ar-
H, Jϭ7.3 Hz); 13C-NMR d: 12.0, 12.2, 14.1, 17.6, 18.6, 21.3, 26.7, 27.3,
27.4, 28.4, 31.4, 31.5, 33.5, 34.8, 35.2, 36.5, 37.9, 39.8, 41.7, 43.2, 43.4,
52.2, 54.7, 55.5, 73.3, 74.7, 77.3, 79.2, 128.2 (ϫ2), 129.4 (ϫ2), 130.7,
132.6, 166.2, 170.5; Anal. Calcd for C36H54O5·0.2H2O: C, 75.80; H, 9.61.
Found: C, 75.77; H, 9.71. Compound 9: [a]D26 ϩ29.6° (cϭ1.04, CHCl3); IR
(neat) 3452, 2947, 2869, 1718, 1603, 1470, 1452 cmϪ1; 1H-NMR d: 0.63 (s,
3H), 0.91 (d, 3H, Jϭ6.8 Hz), 0.96 (d, 3H, Jϭ6.4 Hz), 0.97 (d, 3H,
Jϭ6.4 Hz), 1.08 (s, 3H), 2.02 (s, 3H, –C(O)CH3), 0.87—2.35 (m, 27H), 4.67
(m, 1H, C-3H), 4.96 (m, 1H, C-24H), 7.44 (t, 2H, Ar-H, Jϭ7.8 Hz), 7.55 (t,
1H, Ar-H, Jϭ7.3 Hz), 8.05 (d, 2H, Ar-H, Jϭ7.3 Hz); 13C-NMR d: 11.5,
11.9, 17.6, 18.5, 20.8, 21.1, 21.6, 24.7, 26.9, 27.1, 28.0, 31.2, 31.4, 33.6,
34.9, 35.6, 35.7, 38.5, 42.3, 45.6, 46.3, 48.7, 49.7, 54.4, 54.7, 72.5, 79.0,
1731, 1654, 1560, 1458 cmϪ1 1H-NMR d: 0.68 (s, 3H), 0.94 (d, 3H,
;
Jϭ6.3 Hz), 1.02 (s, 3H), 1.66 (s, 3H), 2.03 (s, 3H, –C(O)CH3), 0.93—2.03
(m, 25H), 2.31—2.33 (m, 2H), 3.83 (s, 3H), 3.89—3.93 (m, 1H, C-3H), 4.56
(ABq, 2H, Jϭ6.8 Hz), 4.59—4.63 (m, 1H, C-24H), 5.37 (d, 1H, olefin-H,
Jϭ4.9 Hz); 13C-NMR d: 11.9, 16.8, 18.7, 19.3, 21.0, 21.4, 24.3, 27.8, 28.2,
30.1, 31.9, 32.0, 35.7, 36.6, 37.0, 38.1, 39.7, 42.3, 50.0, 55.5 (ϫ2), 55.9,
56.7, 74.0, 80.6, 93.6, 113.7, 122.6, 139.7, 144.3, 170.5.
(24R)-3b-Acetoxy-24-t-butyldimethylsilyloxycholesta-5,22-diene (5e)
The t-butyldimethylsilyl compound 5e (165 mg, 58%) was obtained from 4e
(292 mg, 510 mmol) by a similar procedure to that for the benzoyl analogue
5a. mp 86—89 °C; [a]D26 Ϫ31.1° (cϭ1.00, CHCl3); IR (KBr) 2935, 2886,
1
2853, 1736, 1675, 1647, 1472 cmϪ1; H-NMR d: 0.04 (s, 3H), 0.11 (s, 3H),
0.68 (s, 3H), 0.89 (s, 9H), 0.95 (s, 3H), 1.02 (s, 3H), 1.67 (s, 3H), 2.03 (s,
3H, –C(O)CH3), 0.81—2.03 (m, 23H), 2.31—2.33 (m, 2H), 3.95—3.98 (m,