A. Gioiello et al. / Tetrahedron 67 (2011) 1924e1929
1929
(19H, m), 2.02 (3H, s, COCH3), 2.15e2.25 (1H, m, 25-CH), 2.30 (2H,
bt, J 12.0 Hz, 6-CH2), 2.42 (1H, q, J 6.8 Hz, 8-CH), 3.67 (3H, s,
CO2CH3), 4.67 (1H, m, 3-CH); dC (100.6 MHz, CDCl3) 11.6, 12.0, 17.2,
18.6, 21.3, 21.7, 23.7, 24.9, 27.0, 28.3, 33.8, 34.2, 35.4, 35.6, 35.7, 35.9,
38.6, 39.4, 42.4, 45.8, 46.4, 48.8, 49.9, 51.4, 54.9, 54.9, 72.7, 170.4,
177.3, 211.5.
under reduced pressure The residue was purified by flash chro-
matography using 5e40% EtOAc in petroleum ether to afford the
desired compound 2 (68 mg, 0.17 mmol, 87%) as off white solid. Mp:
139e141 ꢀC; Rf (5% MeOH/CHCl3þ0.1% AcOH) 0.42; a1D6 42.6 (c 0.8,
CHCl3); dH (400 MHz, CDCl3) 0.56 (3H, s, 18-CH3), 0.95 (3H, d, J
6.4 Hz, 21-CH3), 1.01 (3H, s, 19-CH3), 1.21 (3H, d, J 6.9 Hz, 27-CH3),
1.25e2.18 (1H, m, CH24), 2.15e2.25 (2H, m, 2-CH2), 2.30e2.35 (1H,
m, 25-CH), 2.42e2.47 (2H, m, 4-CH2), 5.19 (1H, br s, 7-CH); dC
(100.6 MHz, CDCl3) 11.8, 12.4, 17.0, 18.7, 21.6, 22.9, 23.7, 27.9, 30.0,
34.0, 34.3, 35.6, 36.0, 38.1, 38.7, 39.3, 39.4, 42.8, 43.3, 44.2, 48.8,
54.9, 56.0, 117.0, 139.4, 182.1, 212.0. HRMS (ESIþ) m/z 415.3215
[(MþH)þ; calcd for C27H43O3 415.3212].
4.5.4. Methyl 7a-hydroxy-3b-acetoxy-25(S)-methyl-24-bishomo-5a-
cholan-26-oate (16). To a solution of the 7-keto derivative 15
(0.26 g, 0.52 mmol) in dry THF (10 mL) at ꢁ78 ꢀC L-selectrideÒ
(0.8 mL) was added dropwise. The resulting mixture was stirred at
ꢁ78 ꢀC for 2 h, and at ꢁ30 ꢀC for 12 h. A mixture of H2O/EtOH (1:4,
v/v, 20 mL) was added and the reaction mixture was allowed to
warm at 0 ꢀC. At this temperature the reaction was poured into an
aqueous saturated solution of NH4Cl (60 mL), warmed at room
temperature and extracted with EtOAc (3ꢂ40 mL). The combined
organic layers were washed with H2O (50 mL), brine (2ꢂ50 mL),
dried over Na2SO4 and evaporated under reduced pressure. The
crude was purified by flash chromatography eluting with from 5 to
Supplementary data
Supplementary data related to this article can be found online at
InChIKey of the most important compounds described in this
article.
20% EtOAc in petroleum ether to furnish the corresponding 7a-OH
derivative 16 (0.22 g, 0.46 mmol, 88%) as off white solid. Mp:
References and notes
107e109 ꢀC; Rf (15% EtOAc/PET) 0.26; nmax (KBr) 3523, 2944, 2865,
2357, 2138, 1734, 1457, 1375, 1261, 751 cmꢁ1
; dH (400 MHz, CDCl3)
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0.65 (3H, s, 18-CH3), 0.82 (3H, s, 19-CH3), 0.89 (3H, d, J 6.5 Hz, 21-
CH3), 1.01e1.13 (4H, m), 1.16 (3H, d, J 6.5 Hz, 27-CH3), 1.25e1.97
(22H, m), 2.02 (3H, s, COCH3), 2.41e2.46 (1H, m, 25-CH), 3.67 (3H, s,
CO2CH3), 3.82 (1H, bd, J 2.6 Hz, 7-CH), 4.71 (1H, m, 3-CH); dC
(100.6 MHz, CDCl3) 11.1, 11.7, 17.1, 18.5, 20.9, 21.4, 23.6, 23.7, 27.3,
28.1, 33.5, 34.2, 35.5, 35.6, 35.7, 36.2, 36.4, 36.9, 39.4, 39.4, 42.6,
45.7, 50.5, 51.4, 56.0, 67.8, 73.5, 170.5, 177.3. HRMS (ESIþ) m/z
491.3734 [(MþH)þ; calcd for C30H51O5 491.3737].
4.5.5. 3
acid (17)10. Methyl 7
omo-5 -cholan-26-oate (16) (0.16 g, 0.32 mmol) was dissolved in
dry pyridine (6 mL) and SOCl2 (95 mg, 0.80 mmol) was added at
ꢀC. The resulting solution was stirred at room temperature for
b
-Hydroxy-25(S)-methyl-24-bishomo-5
a-chol-7-en-26-oic
a
-hydroxy-3 -acetoxy-25(S)-methyl-24-bish-
b
a
0
48 h, and then cautiously poured into crushed ice (40 mL) and
extracted with Et2O (3ꢂ50 mL). The combined organic phases were
washed with NaHCO3 saturated solution (40 mL), 1
N HCl
(2ꢂ40 mL), H2O (40 mL), brine (40 mL), dried over Na2SO4 and
evaporated under reduced pressure to furnish the corresponding
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D
7-derivative (0.14 g, 0.28 mmol, 90%) that was submitted to hy-
drolysis without further purification. The thus obtained crude was
dissolved into 5% NaOH in MeOH (4 mL) and reacted at room
temperature overnight. The solvent was evaporated under reduced
pressure, the residue was dissolved into H2O (40 mL), washed with
iPr2O (2ꢂ20 mL), acidified with 2 N HCl and extracted with EtOAc
(3ꢂ40 mL). The combined organic layers were washed with H2O
(50 mL), brine (50 mL), dried over Na2SO4 and evaporated under
reduced pressure to yield the desired product 17 (0.11 mg,
0.27 mmol, 96%) as white solid. Mp: 94e96 ꢀC; Rf (5% MeOH/
CHCl3þ0.1% AcOH) 0.28; dH (400 MHz, CDCl3) 0.52 (3H, s, 18-CH3),
0.78 (3H, s, 19-CH3), 0.90 (3H, d, J 6.4 Hz, 21-CH3), 0.92e1.06 (4H,
m), 1.15 (3H, d, J 6.9 Hz, 27-CH3), 1.21e1.97 (23H, m), 2.42e2.51 (1H,
m, 25-CH), 2.50e2.75 (2H, br s, OHþCO2H), 3.64 (1H, m, 3-CH), 5.17
(1H, br s, 7-CH); dC (100.6 MHz, CDCl3) 11.7, 12.9, 17.0, 18.7, 21.4,
22.9, 23.7, 27.8, 29.6, 31.2, 34.10, 34.15, 35.6, 36.0, 37.0, 37.74, 39.2,
39.5, 40.1, 43.3, 49.3, 54.9, 56.0, 70.9, 117.4, 139.5, 180.0.
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7-dafachronic acid (2). A fresh made Jones reagent
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(1.0 mL) was added dropwise to a stirred solution of 17 (80 mg,
0.19 mmol) in acetone (15 mL) at 0 ꢀC and the mixture was stirred at
room temperature for 2 h. Methanol (15 mL) was then added and
the oxidized product was extracted with EtOAc (2ꢂ30 mL). The
combined organic layers were dried over Na2SO4 and evaporated