H.-J. Quan et al. / European Journal of Medicinal Chemistry 37 (2002) 659–669
665
mixture was refluxed for 24 h and filtered. The filtrate
was co-evaporated with toluene under reduced pressure
to give a residue. The residue was dissolved in acetone
5.1.1.5. 26-Cyanoselenopseudodiosgenin (12). To a solu-
tion of 6 (1.45 g, 2.8 mmol) in DMF (130 mL), potas-
sium selenocyanate (2.0 g, 13.9 mmol) was added. The
mixture was stirred for 24 h at 60 °C, and then poured
into ice-cold water (150 mL). The mixture was ex-
tracted with dichloromethane (150 mL×3). The ex-
(
1 mL) and added with a 10% KOH solution (H O–
2
EtOH=1/1) (5 mL), then the mixture was stirred for
4 h at r.t. The mixture was poured into ice-cold water
40 mL) and extracted with dichloromethane (70 mL×
). The extracts were washed with brine, dried over
2
(
3
tracts were washed with 5% NaHCO aqueous solution
3
and brine, dried over anhydrous magnesium sulfate and
filtered. The filtrate was evaporated to obtain a residue
anhydrous magnesium sulfate and then filled. The
filtrate was evaporated and the resulting residue was
that was subjected to a preparative HPLC (15% H O–
2
acetone) to give 12 (0.98 g, 71% yield) as needles, m.p.
purified by a preparative HPLC (15% H O–acetone) to
2
1
06–108 °C (after recrystallization from ethanol):
give 9 (50 mg, yield 71%) as crystalline needles, m.p.
+
1
FABMS: m/z 526 [M+Na] ; H-NMR (CDCl ) (only
2
12–214 °C (after recrystallized from ethanol):
3
+
1
assignable signals were listed) l 5.35 (1H, d, J=5.5 Hz,
H-6), 4.75 (1H, ddd, J=10.1, 7.6, 5.5 Hz, H-16), 3.52
FABMS: m/z 453 [M+Na] ; H-NMR (CDCl ) (only
3
assignable signals were listed) l 5.33 (1H, d, J=5.2 Hz,
H-6), 4.61 (1H, dd, J=15.3, 7.6 Hz, H-16), 3.50 (1H,
m, H-3), 2.52 (1H, dd, J=13.1, 11.6 Hz, H-26a), 2.26
(
2
1H, m, H-3), 3.16 (1H, dd, J=11.9, 5.2 Hz, H-26a),
.95 (1H, dd, J=11.9,7.3 Hz, H-26b), 2.48 (1H, d,
J=10.1 Hz, H-17), 1.60 (3H, s, 21-CH ), 1.07 (3H, d,
3
(1H, dd, J=13.1, 2.1 Hz, H-26b), 1.01 (3H, s, 19-CH3),
J=6.7 Hz, 27-CH ), 1.02 (3H, s, 19-CH ), 0.69 (3H, s,
3
3
1
.00 (3H, d, J=7.3 Hz, 21-CH ), 0.91 (3H, d, J=6.7
3
13
13
18-CH3); C-NMR (CDCl ) l 150.6 (C-22), 140.8 (C-
3
Hz, 27-CH ), 0.82 (3H, s, 18-CH ); C-NMR spectral
3
3
5
), 121.3 (C-6), 104.4 (C-20), 102.0 (SeCN), 84.4 (C-16),
71.6 (C-3), 64.0 (C-17), 54.9 (C-14), 50.0 (C-9), 43.2
C-13), 42.2 (C-4), 39.4 (C-1), 37.6 (C-26), 37.2 (C-12),
6.5 (C-10), 34.0 (C-15), 33.6 (C-25), 33.1 (C-24), 32.1,
C-7), 31.5 (C-2), 31.2 (C-8), 23.1 (C-11), 20.9 (C-23),
9.4 (C-19), 19.2 (C-27), 13.9 (C-18), 11.6 (C-21);
HRMS (FAB) m/z calc. for C H NNaO Se [M+
data were listed in Table 1; HRMS (FAB) m/z calc. for
+
C H O S [M+H] , 431.2983. Found: 431.2968.
2
7
43
3
(
3
(
1
5.1.1.4. 3-O-Benzyl-(3i,20S,22S 25R)-22-thiospirosol-
,
5
-ene (10). To
a
suspension of 3-O-benzyl-26-
thioacetylpseudodiosgenin (1.0 g, 1.8 mmol) in MeOH
200 mL), 10% HCl in MeOH (200 mL) was added.
28
41
2
(
+
Na] , 526.2200. Found: 526.2199.
The mixture was refluxed for 36 h and evaporated
under reduced pressure to give a residue. The residue
was added with ice-cold water (300 mL), and extracted
with dichloromethane (200 mL×3).
The combained extracts were washed with brine,
dried over anhydrous magnesium sulfate and filtered.
The filtrate was evaporated to obtain a residue that was
purified by column chromatography (a gradient of 0–
5.1.1.6. 26,26%-(Bispseudodiosgenyl) diselenide (13). A
solution of 12 (1.50 g, 3.0 mmol) and potassium car-
bonate (1.7 g) in DMF (70 mL) containing water (7.2
mL) was stirred for 8 h at 80 °C. The reaction mixtrue
was acidified with acetic acid, poured into ice-cold
water (250 mL), and then extracted with
dichloromethane (250 mL×3). The combined extracts
2
5
% ethyl acetate in benzene) to obtain 10 (544 mg: yield
6%) as needles, m.p. 149–151 °C (after recrystalliza-
were washed successively with 5% NaHCO aqueous
3
solution and brine, dried over anhydrous magnesium
sulfate, and filtered. The filtrate was evaporated to give
a residue that was recrystallized from EtOH–water to
give 13 (0.91 g, 64% yield) as needles, m.p. 115–
+
1
tion from ethanol): FABMS: m/z 543 [M+Na] ; H-
NMR (CDCl ) (only assignable signals were listed) l
3
7.35–7.24 (5H, aromatic protons), 5.34 (1H, d, J=5.2
Hz, H-6), 4.63 (1H, dd, J=15.3, 7.6 Hz, H-16), 4.55
+
1
1
17 °C: FABMS: m/z 977 [M+Na] ; H-NMR
(
2H, d, J=2.1 Hz, C H CH ), 3.27 (1H, m, H-3), 2.53
6 5 2
(CDCl ) (only assignable signals were listed) l 5.34 (1
3
(1H, dd, J=12.8, 11.6 Hz, H-26a), 2.28 (1H, dd,
H, d, J=5.2 Hz, H-6), 4.74 (1H, ddd, J=10.1, 7.9, 5.8
Hz, H-16), 3.52 (1H, m, H-3), 3.03 (1H, dd, J=11.9,
5.2 Hz, H-26a), 2.83 (1 H, dd, J=11.9, 7.9 Hz, H-26b),
2.47 (1 H, d, J=10.1 Hz, H-17), 1.59 (3H, s, 21-CH3),
1.02 (3H, s, 19-CH ), 1.01 (3H, d, J=6.7 Hz, 27-CH ),
J=12.8, 1.8 Hz, H-26b), 1.03 (3H, s, 19-CH ), 1.01
3
(
3H, d, J=7.0 Hz, 21-CH ), 0.92 (3H, d, J=6.4 Hz,
7-CH ), 0.80 (3H, s, 18-CH ); C-NMR (CDCl ) l
3 3 3
3
1
3
2
1
1
9
6
40.9 (C-5), 138.9 (C H CH ), 128.2 (C H CH ×2),
6
5
2
6
5
2
3
3
13
27.4 (C H CH ×2), 127.3 (C H CH ), 121.2 (C-6),
6
5
2
6
5
2
0.69 (3H, s, 18-CH3); C-NMR (CDCl ) l 151.5 (C-
3
7.4 (C-22), 81.5 (C-16), 78.4 (C-3), 69.8 (C H CH ),
6
5
2
22), 140.8 (C-5), 121.3 (C-6), 103.8 (C-20), 84.3 (C-16),
71.6 (C-3), 64.2 (C-17), 55.0 (C-14), 50.0 (C-9), 43.2
(C-13), 42.2 (C-4), 39.5 (C-1), 39.1 (C-26), 37.2 (C-12),
36.6 (C-10), 34.1 (C-15), 33.9 (C-25), 33.8 (C-24), 32.2
(C-7), 31.6 (C-2), 31.2 (C-8), 23.4 (C-11), 21.0 (C-23),
19.5 (C-27), 19.4 (C-19), 14.0 (C-18), 11.7 (C-21);
HRMS (FAB) m/z calc. for C H NaO Se , [M+
2.7 (C-17), 56.5 (C-14), 50.0 (C-9), 44.3 (C-20), 40.2
(
C-13), 39.7 (C-12), 39.0 (C-4), 38.5 (C-23), 37.1 (C-1),
3
3
1
6.9 (C-10), 33.2 (C-8), 32.0 (C-24, C-26), 31.7 (C-15),
1.3 (C-7, C-25), 28.3 (C-2), 22.4 (C-27), 20.7 (C-11),
9.3 (C-19), 16.4 (C-18), 14.3 (C-21); HRMS (FAB)
+
m/z calc. for C H O S [M+H] , 521.3453. Found:
3
4
49
3
54 82
4
2
+
521.3427.
Na] , 977.4441. Found: 977.4509.