R. Saini et al. / Bioorg. Med. Chem. 21 (2013) 5794–5798
5797
chloride (134 mg, 3.17 mmol) in THF (10 mL) at 25 °C. The result-
ing reaction mixture was stirred at 25 °C for 1 h. A solution of
728, 569 cm–1. 1H NMR (600 MHz, CDCl
3
): d = 0.68 (s, 3H), 0.90–
0.96 (m, 1H), 0.95 (d, J = 6.5 Hz, 3H), 0.98–1.02 (m, 1H), 1.00 (s,
3H), 1.04–1.19 (m, 5H), 1.22–1.26 (m, 1H), 1.28 (t, J = 7.1 Hz,
3H), 1.40–1.61 (m, 8H), 1.80–1.86 (m, 3H), 1.82 (s, 3H), 1.94–
2.02 (m, 2H), 2.03–2.09 (m, 1H), 2.17–2.25 (m, 2H), 2.29–2.30
(m, 1H), 3.52 (m, 1H), 4.18 (q, J = 7.1 Hz, 2H), 5.35 (m, 1H), 6.74
6
b
aldehyde 5
(1.00 g, 2.11 mmol) in THF (20 mL) was added
slowly and the reaction mixture was stirred at 25 °C for 16 h.
Upon completion of the reaction, water (100 mL) was added at
2
5 °C, the aqueous layer was extracted with diethyl ether
1
3
(
3 Â 250 mL), the combined organic layers were dried over so-
(dt, J = 1.0, 7.4 Hz, 1H). C NMR and DEPT (150 MHz, CDCl
d = 12.02 (CH ), 12.43 (CH ), 14.44 (CH ), 18.68 (CH ), 19.54
), 21.21 (CH ), 24.42 (CH ), 25.59 (CH ), 28.34 (CH ), 31.79
), 32.03 (CH and CH), 34.85 (CH ), 35.84 (CH), 36.64 (C),
), 39.90 (CH ), 42.43 (CH ), 42.52 (C), 50.23 (CH),
56.04 (CH), 56.87 (CH), 60.52 (CH ), 71.92 (CH), 121.80 (CH),
3
):
dium sulfate and the solvent was evaporated. Purification of the
residue by column chromatography on silica gel (pentane–
3
3
3
3
(CH
(CH
3
2
2
2
2
2
CH Cl
2
–Et
2
O, gradient elution from 110:5:1 to 60:5:1) provided
2
2
2
the (E)-isomer 7 (949 mg, 81%) as colourless crystals, mp 123–
37.39 (CH
2
2
2
1
1
CDCl
24 °C. IR (ATR):
274, 1252, 1094, 869, 835, 773, 743 cm
): d = 0.05 (s, 6H), 0.67 (s, 3H), 0.85–0.93 (m, 1H), 0.88 (s,
m
= 2934, 2882, 2856, 1712, 1652, 1469, 1367,
2
–1 1
.
H NMR (600 MHz,
127.56 (C), 140.91 (C), 143.01 (CH), 168.51 (C@O). MS (EI): m/z
+
3
(%) = 442 (9) [M ], 424 (13), 409 (12), 299 (44), 271 (100), 253
9H), 0.95 (d, J = 6.5 Hz, 3H), 0.97–1.02 (m, 1H), 1.00 (s, 3H),
1.02–1.21 (m, 5H), 1.23–1.27 (m, 1H), 1.20 (t, J = 7.1 Hz, 3H),
1.41–1.60 (m, 8H), 1.69–1.73 (m, 1H), 1.79–1.86 (m, 2H), 1.83
(75), 213 (30), 159 (23), 145 (30), 121 (20), 107 (26), 105 (30),
95 (29). Elemental analysis calcd for C29
found: C 78.82, H 10.82.
46 3
H O : C 78.68, H 10.47;
(
3
s, 3H), 1.94–2.02 (m, 2H), 2.03–2.09 (m, 1H), 2.15–2.29 (m,
H), 3.48 (m, 1H), 4.17 (q, J = 7.1 Hz, 2H), 5.31 (m, 1H), 6.74 (t,
3.4. Ethyl (24Z)-3b-hydroxycholesta-5,24-dien-26-oate (10)
1
3
J = 7.4 Hz, 1H). C NMR and DEPT (150 MHz, CDCl
3
): d = À4.44
(
(
(
(
4
7
1
2CH
CH ), 19.58 (CH
3CH ), 28.36 (CH
CH ), 35.85 (CH), 36.73 (C), 37.53 (CH
2.96 (CH
3
), 12.02 (CH
), 21.20 (CH
), 32.05 (CH), 32.06 (CH
3
), 12.44 (CH
3
), 14.45 (CH
3
), 18.42 (C), 18.69
A 1.0 M solution of TBAF in THF (0.379 mL, 379
lmol) was
3
3
2
), 24.43 (CH
2
), 25.58 (CH
), 32.23 (CH
2
), 26.09
), 34.86
added to a solution of 8 (141 mg, 253 mol) in THF (5 mL) at
l
3
2
2
2
25 °C and the mixture was stirred at 65 °C for 3 h. After cooling
to 25 °C, water (20 mL) was added and the aqueous layer was ex-
tracted with ethyl acetate (3 Â 100 mL). The combined organic lay-
ers were dried over sodium sulfate and the solvent was evaporated.
Purification of the residue by column chromatography on silica gel
(pentane–CH Cl –ethyl acetate, 10:5:2) provided 10 (100 mg, 90%)
2 2
as colourless crystals, mp 86–89 °C. IR (ATR): d = 3488, 2934, 2898,
2
2
), 39.93 (CH
2
), 42.54 (C),
),
2
), 50.33 (CH), 56.04 (CH), 56.92 (CH), 60.51 (CH
2
2.78 (CH), 121.27 (CH), 127.56 (C), 141.72 (C), 143.01 (CH),
+
68.51 (C@O). MS (EI): m/z (%) = 556 (<1) [M ], 541 (2)
+
+
(
[MÀCH
3
] ), 499 (100) ([MÀt-Bu] ), 481 (2), 453 (2), 379 (3),
53 (4), 159 (7), 95 (9), 75 (31). Elemental analysis calcd for
Si: C 75.84, H 11.86; found: C 75.59, H 11.09.
The (Z)-isomer 8 was obtained as the more polar fraction as col-
ourless crystals (166 mg, 14%), mp 120–121 °C. IR (ATR): = 2933,
882, 2857, 1714, 1641, 1458, 1370, 1247, 1220, 1177, 1133, 1090,
2
C
35
H
60
O
3
2861, 1713, 1650, 1450, 1369, 1310, 1218, 1195, 1143, 1099, 1070,
–
1 1
1052, 953, 838, 803, 774, 742 cm
3
. H NMR (500 MHz, CDCl ):
m
d = 0.67 (s, 3H), 0.90–0.95 (m, 1H), 0.94 (d, J = 6.6 Hz, 3H), 0.97–
1.01 (m, 1H), 1.00 (s, 3H), 1.03–1.18 (m, 5H), 1.22–1.27 (m, 1H),
1.30 (t, J = 7.2 Hz, 3H), 1.39–1.61 (m, 8H), 1.80–1.86 (m, 3H), 1.88
(d, J = 0.8 Hz, 3H), 1.94–2.02 (m, 2H), 2.20–2.39 (m, 3H), 2.45–
2.52 (m, 1H), 3.52 (m, 1H), 4.20 (q, J = 7.2 Hz, 2H), 5.35 (m, 1H),
2
1
025, 961, 889, 870, 835, 774 cm–1
1
3
. H NMR (600 MHz, CDCl ):
d = 0.05 (s, 6H), 0.67 (s, 3H), 0.87–0.91 (m, 1H), 0.88 (s, 9H), 0.94
d, J = 6.5 Hz, 3H), 0.97–1.02 (m, 1H), 0.99 (s, 3H), 1.03–1.17 (m,
(
1
3
5H), 1.19–1.27 (m, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.39–1.60 (m, 8H),
1.69–1.73 (m, 1H), 1.78–1.86 (m, 2H), 1.88 (d, J = 1.1 Hz, 3H),
1.94–2.01 (m, 2H), 2.14–2.18 (m, 1H), 2.26 (m, 1H), 2.21–2.38
5.89 (dt, J = 7.4, 1.2 Hz, 1H). C NMR and DEPT (125 MHz, CDCl
d = 12.01 (CH ), 14.47 (CH ), 18.69 (CH ), 19.55 (CH ), 20.87 (CH
21.21 (CH ), 24.43 (CH ), 26.53 (CH ), 28.36 (CH ), 31.79 (CH
32.03 (CH and CH), 35.78 (CH
(CH ), 39.87 (CH ), 42.43 (CH ), 42.50 (C), 50.23 (CH), 56.07 (CH),
56.87 (CH), 60.17 (CH ), 71.94 (CH), 121.83 (CH), 126.90 (C),
3
):
3
3
3
3
3
),
),
2
2
2
2
2
(
5
m, 1H), 2.45–2.52 (m, 1H), 3.48 (m, 1H), 4.19 (q, J = 7.1 Hz, 2H),
2
2
), 35.85 (CH), 36.64 (C), 37.38
.31 (m, 1H), 5.89 (dt, J = 7.4, 1.2 Hz, 1H). 13C NMR and DEPT
2
2
2
(
150 MHz, CDCl
3
): d = À4.44 (2CH
8.42 (C), 18.70 (CH ), 19.58 (CH
4.44 (CH ), 26.09 (3CH
3
), 12.00 (CH
), 20.86 (CH
), 26.53 (CH ), 28.36 (CH
), 35.80 (CH ), 35.85 (CH), 36.73 (C),
), 42.52 (C), 42.97 (CH ), 50.34 (CH),
), 72.79 (CH), 121.29 (CH),
26.91 (C), 141.73 (C), 143.68 (CH), 168.41 (C@O). MS (EI): m/z
3
), 14.47 (CH
3
),
),
2
1
2
3
3
5
1
3
3
3
), 21.20 (CH
2
140.90 (C), 143.71 (CH), 168.42 (C@O). MS (EI): m/z (%) = 442
+
2
3
2
2
2
2
), 32.05 (CH),
(12) [M ], 424 (15), 409 (13), 299 (45), 271 (100), 253 (73), 213
2.08 (CH
7.53 (CH
2
), 32.23 (CH
), 39.92 (CH
2
(37), 161 (18), 145 (30), 128 (39), 95 (36), 79 (25), 55 (27). Elemen-
2
2
46 3
tal analysis calcd for C29H O : C 78.68, H 10.47; found: C 78.68, H
6.10 (CH), 56.93 (CH), 60.16 (CH
2
10.46.
+
+
+
(
4
%) = 556 (<1) [M ], 541 (2) ([MÀCH
3
] ) 499 (100) ([MÀt-Bu] ),
3.5. (24E)-Cholesta-5,24-diene-3b,26-diol ((24E)-26-
hydroxydesmosterol) (2)
81 (2), 379 (5), 253 (3), 213 (3), 159 (9), 95 (13), 75 (39). Elemen-
tal analysis calcd for C35
H 11.03.
H O Si: C 75.48, H 10.86; found: C 75.24,
60 3
A 1.0 M solution of DIBAL-H in CH
was added at À78 °C to a solution of 9 (523 mg, 1.18 mmol) in
CH Cl (10 mL) and diethyl ether (10 mL) and the mixture was stir-
2 2
Cl (4.14 mL, 4.14 mmol)
3
.3. Ethyl (24E)-3b-hydroxycholesta-5,24-dien-26-oate (9)
2
2
red at that temperature for 1 h and at À20 °C for 30 min. Water
(25 mL) was added at À10 °C. The aqueous layer was extracted
with ethyl acetate (3 Â 100 mL), the combined organic layers were
dried over sodium sulfate and the solvent was evaporated. Purifica-
tion of the residue by column chromatography on silica gel (pen-
A 1.0 M solution of TBAF in THF (2.45 mL, 2.45 mmol) was
added to a solution of 7 (910 mg, 1.63 mmol) in THF (20 mL) at
5 °C and the mixture was stirred at 65 °C for 3 h. After cooling
to 25 °C, water (25 mL) was added and the aqueous layer was ex-
tracted with ethyl acetate (3 Â 100 mL). The combined organic
layers were dried over sodium sulfate and the solvent was evap-
orated. Purification of the residue by column chromatography
2
tane–CH
colourless crystals, mp 183–184 °C. IR (ATR):
2902, 2860, 1437, 1358, 1334, 1225, 1192, 1109, 1063, 1022,
2
Cl
2
–ethyl acetate, 1:1:1) provided 2 (464 mg, 98%) as
m
= 3219 (br), 2930,
–
1 1
on silica gel (pentane–CH
2
Cl
2
–ethyl acetate 20:5:4) provided 9
3
953, 802, 733, 633, 602 cm . H NMR (600 MHz, CDCl ): d = 0.68
(
m
1
648 mg, 90%) as colourless crystals, mp 88–89 °C. IR (ATR):
= 3499, 3474, 2935, 2899, 2855, 1715, 1686, 1652, 1462, 1369,
296, 1276, 1237, 1196, 1136, 1100, 1067, 1022, 957, 839, 798,
(s, 3H), 0.90–0.96 (m, 1H), 0.94 (d, J = 6.5 Hz, 3H) 0.98–1.02 (m,
1H), 1.01 (s, 3H), 1.04–1.13 (m, 4H), 1.16 (dt, J = 4.6, 12.8 Hz, 1H),
1.23–1.29 (m, 1H), 1.38–1.60 (m, 8H), 1.67 (s, 3H), 1.80–1.86 (m,