5896
G.-P. Zhang et al. / Tetrahedron 67 (2011) 5894e5896
4.2. General experimental procedure
evaporated. The resulting precipitate was filtered, washed with
water, and dried. The crude product 26-azide-pseudodiosgenin
(0.80 g, 98%) was used in next step without further purification.
To a solution of 26-azide-pseudodiosgenin (0.70 g,1.60 mmol) in
CH3CN, NaI (0.50 g, 2 equiv) was added. After 30 min, a solution of
Me3SiCl (0.45 mL, 2 equiv) in CH3CN was added dropwise, and the
resulting yellow mixture was stirred at rt for 2 h. Then the reaction
was quenched with 10% aqueous Na2S2O3, and then 5 N NaOH was
added to adjust the pH to 9. After removal of CH3CN, the mixture
was extracted with CHCl3. The organic layer was washed with
water and brine, dried over sodium sulfate, and concentrated to
give yellow solid. The solid was recrystallized in ethanol to give
4.2.1. 3-Ac-26-TFA-pseudodiosgenin (2). The mixture of diosgenin 1
(5.00 g, 12.08 mmol), acetic anhydride (6 mL), and pyridine (10 mL)
was stirred at rt for 6 h, and then was poured into water. The
resulting white precipitate was filtered, and washed with water for
three times. The crude product 3-Ac-diosgenin (5.30 g) was used in
next step without further purification.
To a solution of 3-Ac-diosgenin (4.50 g, 9.87 mmol) in dried
CH2Cl2 was added TFAT (3.65 g,1.5 equiv) at ꢁ40 ꢀC. The mixture was
stirred for 3 h, and then quenched with water. Dilution with CH2Cl2,
the organic layer was washed with water and brine, dried over so-
dium sulfate, and concentratedtoyield white solid 2 (4.98 g, 90% two
steps). The crude product 2 was used in next step without further
solasodine 5 (0.45 g, 72%); mp 198e200 ꢀC; ½a D20
ꢁ98 (c 0.35,
ꢂ
methanol); 1H NMR (400 MHz, CDCl3):
d
5.34 (d, J¼4.8 Hz, 1H),
purification; 1H NMR (400 MHz, CDCl3):
d
5.37 (d, J¼4.8 Hz, 1H),
4.33e4.30 (m, 1H), 3.55e3.47 (m, 1H), 2.18e2.57 (m, 1H), 2.00e2.18
(m, 4H), 1.58 (s, 3H), 1.02 (s, 3H), 0.98 (d, J¼7.2 Hz, 3H), 0.84 (d,
4.69e4.75 (m, 1H), 4.58e4.62 (m, 1H), 4.22 (dd, J¼10.8, 5.8 Hz, 1H),
4.15 (dd, J¼10.8, 6.6 Hz, 1H), 2.45 (d, J¼10.8 Hz, 1H), 2.22 (d,
J¼10.2 Hz, 2H), 2.05e2.18 (m, 4H), 2.00 (s, 3H), 1.58 (s, 3H), 1.04 (s,
3H), 0.98 (d, J¼6.6 Hz, 3H), 0.68 (s, 3H); MS (ESI) m/z 575.5 [MþNa]þ;
HRMS (ESI) m/z 575.2968 [MþNa]þ (calcd for C26H30NaO7,
575.2960).
J¼6.0 Hz, 3H), 0.81 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 140.77,
121.38, 98.24, 78.80, 71.68, 62.67, 56.46, 50.01, 47.57, 42.22, 41.20,
40.48, 39.89, 37.18, 36.60, 33.97, 32.12, 31.57, 31.36, 31.27, 30.19,
20.85, 19.39, 19.28, 16.40, 15.26; MS (ESI) m/z 414.5 [MþH]þ; HRMS
(ESI) m/z 414.3375 [MþH]þ (calcd for C26H31O7, 414.3372).
4.2.2. 3-Ac-pseudodiosgenin (3). The solid 3-Ac-26-TFA-pseudo-
diosgenin 2 (2.00 g, 3.6 mmol) was dissolved in methanol (10 mL),
and then saturated aqueous NaHCO3 (20 mL) was added. After
stirring for 3 h, methanol was evaporated. The resulting precipitate
was filtered, washed with water, and dried in oven. The crude
product 3 (1.61 g, 98%) was used in next step without further pu-
Acknowledgements
This work was supported by the Chinese National Science and
Technology Major Project ‘Key New Drug Creation and Manufacturing
Program’(Grants 2009ZX09301-001, 2009ZX09102-022), the National
Natural Science Foundation of China (Grants 21002027, 90713046, and
30925040), and CAS Foundation (Grant KSCX2-YW-R-179).
rification; 1H NMR (400 MHz, CDCl3):
d
5.37 (d, J¼4.8 Hz, 1H),
4.64e4.78 (m, 1H), 4.58e4.62 (m, 1H), 3.40e3.54 (m, 1H), 2.45 (d,
J¼10.8 Hz, 1H), 2.28 (d, J¼12.8 Hz, 2H), 2.03e2.20 (m, 4H), 2.00 (s,
3H), 1.55 (s, 3H), 1.03 (s, 3H), 0.94 (d, J¼6.6 Hz, 3H), 0.76 (s, 3H); MS
(ESI) m/z 479.5 [MþNa]þ; HRMS (ESI) m/z 479.3140 [MþNa]þ (calcd
for C26H30NaO7, 479.3137).
Supplementary data
Supplementary data associated with this article can be found, in
4.2.3. 3-Ac-26-azide-pseudodiosgenin (4). To a solution of 3-acetyl
pseudodiosgenin 3 (1.20 g, 2.6 mmol) in pyridine (5 mL) and
CH2Cl2 (25 mL) was added TsCl (0.60 g, 2 equiv) at ꢁ30 ꢀC in two
portions. After conversion was completed indicated by TLC, the
mixture was washed with 2 N HCl and brine. The organic layer was
dried by sodium sulfate and concentrated to afford yellow solid 3-
Ac-26-Ts-pseudodiosgenin (1.50 g, 95%). The crude product was
used in next step without further purification.
A mixture of 3-Ac-26-Ts-pseudodiosgenin (1.30 g, 2.1 mmol)
and NaN3 (0.40 g, 3 equiv) in DMF was heated to 60 ꢀC for 3 h. Then
ice-water was added to the mixture at rt. After 15 min, the resulting
precipitate was filtered, washed with water, and dried. The crude
product 4 (0.94 g, 93%) was used in next step without further pu-
References and notes
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rification; 1H NMR (400 MHz, CDCl3):
d
5.37 (d, J¼4.8 Hz, 1H),
4.78e4.73 (m, 1H), 4.58e4.72 (m, 1H), 3.22 (dd, J¼12.0, 5.7 Hz, 1H),
3.10 (dd, J¼12.0, 4.8 Hz, 1H), 2.47 (d, J¼10.8 Hz, 1H), 2.30 (d,
J¼10.8 Hz, 2H), 2.05e2.18 (m, 4H), 2.02 (s, 3H), 1.58 (s, 3H), 1.04 (s,
3H), 0.96 (d, J¼6.6 Hz, 3H), 0.68 (s, 3H); MS (ESI) m/z 481.7
[MþNa]þ; HRMS (ESI) m/z 481.3328 [MþNa]þ (calcd for
C26H30NaO7, 481.3304).
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4.2.4. Solasodine (5). The solid 3-Ac-26-azide-pseudodiosgenin 4
(0.90 g, 1.87 mmol) was dissolved in methanol (10 mL), and then
5 N NaOH (4 mL) was added. After stirring for 1 h, methanol was