70
R.N. Kumar, S. Lee / Steroids 118 (2017) 68–75
2.2.2. 12b-Benzyloxy-3,22-dihydroxy-5
a
-furostan-14,16-diene (9)
2.2.4. 12b-Benzyloxy-3,22-diketo-14,17-peroxo-5a-furostan-15-ene
Potassium carbonate (2.2 g, 15.7 mmol) was added to the stir-
red solution of olefin 8 (4.4 g, 7.85 mmol) in methanol (50 mL)
and stir the reaction mixture at rt for 2 h. After the completion of
the reaction, analyzed by TLC, the methanol was evaporated, the
product was extracted with dichloromethane (100 mL) and
(11)
Diene 10 (3.46 g, 6.72 mmol) in CH2Cl2 (40 mL) was cooled to
ꢂ78 °C. Tetraphenylporphine (5 mg, 0.1 mol%) was added to the
solution and then oxygen was bubbled into the solution via a bal-
loon with photoactivation (GE Sunlamp 300 W) at a distance of
approximately 8–9 in. from the reaction flask. The reaction was
stirred under sunlamp irradiation at ꢂ78 °C for 2 h. The reaction
solvent was evaporated and the crude peroxides (11a and 11b)
were directly used in the next step without further purification.
Rf = 0.35 (petroleum ether–EtOAc, 7:3). 1H NMR (400 MHz,
CDCl3): 8.02 (Abq, J = 7.0 Hz, 2H), 7.57 (tt, J = 7.4, 1.6 Hz, 1H),
7.44 (td, J = 7.4, 1.6 Hz, 1H), 6.76 (d, J = 5.9 Hz, 1H), 6.39 (d,
J = 6.3 Hz, 1H), 5.69 (dd, J = 11.7, 5.1 Hz, 1H), 4.54–4.51 (m, 1H),
4.29–4.25 (m, 1H), 3.03 (q, J = 8.2 Hz, 1H), 2.48–2.37 (m, 2H),
2.37–2.28 (m, 2H), 2.28–2.22 (m, 2H), 2.17–2.10 (m, 2H), 2.10–
2.04 (m, 2H), 2.00–1.90 (m, 2H), 1.88–1.82 (m, 1H), 1.68–1.57
(m, 1H), 1.53–1.48 (m, 1H), 1.47 (s, 3H), 1.45–1.36 (m, 2H), 1.30–
1.23 (m, 2H), 1.21 (d, J = 7.0 Hz, 3H), 1.04 (s, 3H), 1.02 (s, 3H). 13C
NMR (100 MHz, CDCl3): 210.9 (AC3@OA), 209.8 (AC22@OA),
165.3 (AC@O, Bz), 135.3 (AC25A), 133.3 (ACHA, Bz), 131.6
(ACHA, Bz), 129.5 (AC16HA), 128.7 (AC15HA), 110.1 (AC26HA),
98.2 (AC17A), 96.7 (AC14A), 71.0 (AC12HA), 63.8 (AC20HA),
45.5 (AC13A), 45.0 (AC10A), 44.2 (AC4H2A), 43.0 (AC5HA), 41.1
(AC9HA), 38.0 (AC2H2A), 37.7 (AC1H2A), 35.7 (AC23H2A), 33.4
(AC8HA), 30.5 (C24H2A), 28.7 (AC7H2A), 26.9 (AC6H2A), 26.7
(AC11H2A), 22.5 (AC18H3A), 15.1 (AC27H3A), 13.1(AC19H3A),
10.8 (AC18H3A); MS (ESI): m/z = 569 [M+Na]+. HRMS: calcd. for
washed with
a saturated solution of ammonium chloride
(30 mL). The organic phase was dried with sodium sulfate, filtered
and evaporated. The crude product was subjected to silica gel chro-
matography using hexane–ethyl acetate (1:1) to give diol 9
(7.23 mmol, 3.74 g. 92%) as white solid (m.p. 78–80 °C).
Rf = 0.5 (petroleum ether–EtOAc, 1:1); 1H NMR (300 MHz,
CDCl3): 8.08 (ABq, J = 8.6 Hz, 2H), 7.59 (tt, J = 7.4, 1.6 Hz, 1H),
7.47 (tt, J = 7.4, 1.6 Hz, 2H), 6.20 (d, J = 2.0 Hz, 1H), 5.96 (t,
J = 2.0 Hz, 1H), 4.69–4.66 (m, 1H), 4.65–4.62 (m, 1H), 4.44 (dd,
J = 11.0, 4.3 Hz, 1H), 3.60 (d, J = 5.1 Hz, 1H), 3.56 (td, J = 8.6,
2.3 Hz, 1H), 2.57 (dq, J = 8.6, 7.0 Hz, 1H), 2.27–2.18 (m, 1H), 2.18–
2.11 (m, 1H), 2.10–2.04 (m, 1H), 2.04–1.97 (m, 1H), 1.85–1.75
(m, 2H), 1.75–1.69 (m, 2H), 1.69 (s, 3H), 1.63 (dquin, J = 12.5,
2.3 Hz, 2H), 1.56–1.45 (m, 1H), 1.46–1.39 (m, 3H), 1.39–1.31 (m,
2H), 1.27 (s, 3H), 1.22–1.12 (m, 1H), 1.06 (td, J = 13.3, 3.5 Hz, 1H),
0.91 (s, 3H), 0.88–0.81 (m, 1H), 0.80 (d, J = 6.7 Hz, 3H). 13C NMR
(100 MHz, CDCl3): 171.2 (AC@O, Bz), 160.0 (AC14A), 156.3
(AC17A), 146.0 (AC25A), 133.1 (ACHA, Bz), 130.5 (ACHA, Bz),
129.4 (AC15HA), 128.5 (ACHA, Bz), 124.9 (AC16HA), 120.7
(ACHA, Bz), 109.8 (AC26HA), 79.3 (AC12HA), 75.4 (AC22HA),
71.0 (AC3HA), 57.1 (AC13A), 53.3 (AC10A), 44.5 (AC20HA),
39.2 (AC5HA), 37.9 (AC8HA), 35.8 (AC9HA), 34.8 (AC4H2A),
33.5 (AC23H2A), 31.9 (AC1H2A), 31.3 (AC24H2A), 29.2 (AC2H2A),
28.2 (AC6H2A), 27.4 (AC18H3A), 27.2 (AC11H2A), 22.5 (AC7H2),
21.3 (AC27H3A), 14.3 (AC21H3A), 12.3 (AC19H3A); MS (ESI):
m/z = 541 [M+Na]+. HRMS: calcd. for C34H46O4Na [M+Na]+:
541.3294: found: 541.3297.
C
34H42NaO6 [M+Na]+: 569.2879: found: 569.2882.
2.2.5. 12b-Benzyloxy-3,22-diketo-14,17-dihydroxy-5
ene (12)
a-furostan-15-
To the crude peroxides (11a and 11b) in CH2Cl2 (40 mL) was
added activated Zn powder (4.3 g, 67.2 mmol) and AcOH
(4.3 mL). The mixture was stirred at rt for 2 h. Aqueous NaHCO3
(10 mL) was added to quench the reaction. The organic layer was
separated and the aqueous phase was extracted with CH2Cl2
(3 ꢁ 100 mL). The combined extracts were dried over anhydrous
Na2SO4, concentrated under reduced pressure, and purified by
chromatography on silica gel to provide 12a and 12b as white solid
2.2.3. 12b-Benzyloxy-3,22-diketo-5a-furostan-14,16-diene (10)
Add IBX (4.86 g, 17.4 mmol) to the stirred solution of diol 9
(3.74 g, 7.23 mmol) in EtOAc (80 mL) at rt, then reflux the reaction
mixture at 94 °C for 5 h and check TLC for the completion of reac-
tion. After completion of reaction, quench with saturated aqueous
NaHCO3 (50 mL) and the mixture stirred for another 30 min. The
organic layer was extracted with EtOAc (3 ꢁ 100 mL), and the com-
bined extracts were dried over MgSO4 and rotary evaporated to
give the corresponding crude diketo 10. Purification of the crude
product by column chromatography using 5:1 petroleum ether–
EtOAc as an eluent gave 10 (3.46 g, 6.72 mmol, 93%) as white solid
(m.p. 83–84 °C).
(a
isomer, 1.99 g, 54%, m.p. 188–189 °C) and b isomer (1.36 g, 37%).
12a (
a
isomer): Rf = 0.3 (petroleum ether–EtOAc, 7:3). 1H NMR
(400 MHz, CDCl3): 8.06, 8.04 (Abq, J = 1.6 Hz, 2H), 7.57 (tt, J = 7.4,
1.6 Hz, 1H), 7.45 (tt, J = 7.4, 1.6 Hz, 2H), 6.31 (d, J = 5.9 Hz, 1H),
6.11 (dd, J = 10.2, 5.9 Hz, 1H), 5.79 (d, J = 5.9 Hz, 1H), 5.01 (s, 1H),
4.73–4.70 (m, 1H), 4.62–4.59 (m, 1H), 3.88 (s, 1H), 2.84 (q,
J = 7.0 Hz, 1H), 2.73–2.63 (m, 1H), 2.58–2.48 (m, 1H), 2.36–2.26
(m, 2H), 2.26–2.17 (m, 3H), 2.15–2.06 (m, 2H), 1.96–1.87 (m,
3H), 1.76–1.70 (m, 1H), 1.70 (s, 3H), 1.67–1.61 (m, 1H), 1.60–1.53
(m, 2H), 1.51–1.41 (m, 2H), 1.36 (td, J = 12.9, 3.9 Hz, 1H), 1.09 (s,
3H), 1.08 (s, 3H), 1.07 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3): 216.7 (AC3@OA), 211.4 (AC22@OA), 165.7 (AC@O, Bz),
138.1 (AC25A), 137.8 (ACHA, Bz), 133.0 (ACHA, Bz), 130.7
(AC16HA), 129.6 (AC15HA), 128.4 (ACHA, Bz), 110.4 (AC26HA),
88.6 (AC17A), 87.3 (AC14A), 71.3 (AC12HA), 54.6 (AC20HA),
47.9 (AC13A), 46.0 (AC10A), 45.2 (AC4H2A), 44.5 (AC5HA),
41.1 (AC9HA), 37.9 (AC2H2A), 34.7(AC1H2A), 30.9 (AC23H2A),
28.8 (AC8HA), 26.9 (AC24H2A), 26.0 (AC7H2A), 22.7 (AC6H2A),
14.8 (AC11H2A), 12.3 (AC18H3A, AC27H3A), 10.8 (AC19H3A,
Rf = 0.4 (petroleum ether–EtOAc, 7:3); 1H NMR (400 MHz,
CDCl3): 8.08 (dd, J = 8.6, 1.6 Hz, 2H), 7.58 (dt, J = 7.4, 1.2 Hz, 1H),
7.47 (d, J = 7.0 Hz, 2H), 6.11 (d, J = 2.0 Hz, 1H), 5.95 (t, J = 2.0 Hz,
1H), 4.67–4.63 (m, 1H), 4.58–4.55 (m, 1H), 4.44 (dd, J = 11.3,
4.3 Hz, 1H), 3.50 (dd, J = 13.7, 6.6 Hz, 1H), 2.62–2.51 (m, 1H),
2.51–2.42 (m, 1H), 2.39–2.13 (m, 7H), 2.13–1.93 (m, 3H), 1.66 (s,
3H), 1.64–1.52 (m, 2H), 1.51–1.34 (m, 4H), 1.31 (s, 3H), 1.09 (s,
3H), 1.03 (d, J = 6.6 Hz, 3H), 0.88 (m, 1H). 13C NMR (100 MHz,
CDCl3): 210.9 (AC3@OA), 209.5 (AC22@OA), 165.5 (AC@O, Bz),
156.0 (AC14A), 154.6 (AC17A), 144.6 (AC25A), 133.2 (ACHA,
Bz), 130.3 (ACHA, Bz), 129.4 (AC15HA), 128.6 (ACHA, Bz), 127.6
(AC16HA), 121.5 (ACHA, Bz), 110.0 (AC26HA), 78.8 (AC12HA),
56.9 (AC20HA), 52.5 (AC13A), 46.0 (AC10A), 44.4 (AC4H2A),
38.5 (AC5HA), 38.4 (AC13HA), 37.8 (AC9HA), 35.9 (AC2H2A),
34.7 (AC1H2A), 31.8 (AC23H2A), 28.8 (AC8HA), 28.4 (C24H2A),
27.5 (AC7H2A), 22.6 (AC6H2A), 18.0 (AC11H2A), 14.4 (AC18H3A,
AC27H3A), 11.5 (AC19H3A, AC18H3A); MS (ESI): m/z = 537 [M
+Na]+. HRMS: calcd. for C34H42NaO4 [M+Na]+: 537.2981: found:
537.2978.
AC18H3A); MS (ESI): m/z = 571 [M+Na]+. HRMS: calcd. for C34H44
-
NaO6 [M+Na]+: 571.3036: found: 571.3024.
12b (b isomer): Rf = 0.3 (petroleum ether–EtOAc, 7:3). 1H NMR
(400 MHz, CDCl3): 8.01, 7.99 (Abq, J = 1.6 Hz, 2H), 7.59 (tt, J = 7.4,
1.6 Hz, 1H), 7.46 (tt, J = 7.4, 1.6 Hz, 2H), 6.44 (d, J = 6.3 Hz, 1H),
6.12 (d, J = 6.3 Hz, 1H), 5.74 (s, 1H), 4.88 (dd, J = 11.3, 4.7 Hz, 1H),
4.39–4.35 (m, 1H), 4.02–3.98 (m, 1H), 3.68 (s, 1H), 2.75 (q,