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L.-Q. Shen et al. / Steroids 77 (2012) 1398–1402
J = 7.8 Hz, 1H), 4.62 (broad s, 1H), 3.68 (s, 3H), 3.04 (dd, J = 13.8,
3.6 Hz, 1H), 2.64 (m, 1H), 2.58 (m, 1H), 2.48–2.43 (m, 2H), 2.17
(m, 1H), 2.14 (s, 3H), 2.03 (dt, J = 13.2, 2.4 Hz, 1H), 1.86–1.79 (m,
3H), 1.54 (dd, J = 13.2, 3.6 Hz, 1H),1.47–1.42 (m, 3H), 1.28–1.21
(m, 2H), 0.72 (s, 3H). 13C NMR (150 MHz, CDCl3): d = 174.9, 153.1,
138.7, 128.8, 127.7, 126.9, 113.0, 55.6, 55.2, 51.4, 45.03, 45.01,
40.4, 39.4, 29.3, 26.43, 26.40, 24.4, 23.9, 19.4, 14.3. HRMS: [M+]
calcd for C21H28O3: 328.2038; found: 328.2032.
H2O and 10 mL of brine, dried and concentrated in vacuo. The res-
idue was flash-chromatographed (5–10% ethyl acetate in petro-
leum ether) to give 11. Yield: 0.179 g (90%); yellow oil. 1H NMR
(600 MHz, CDCl3): d = 9.80 (s, 1H),6.92 (d, J = 7.8 Hz, 1H), 6.61 (d,
J = 7.8 Hz, 1H), 6.04 (m, 1H), 5.41 (dd, J = 17.4, 1.8 Hz, 1H), 5.25
(dd, J = 10.8, 1.8 Hz, 1H), 4.48 (d, J = 4.8 Hz, 2H), 3.10 (dd, J = 10.8,
3.0 Hz, 1H), 2.66–2.55 (m, 2H), 2.50 (t, J = 9.6, 1H), 2.37 (t, J = 9.6,
1H), 2.19–2.17 (m, 1H), 2.15 (s,1H),2.03 (dt, J = 10.8, 3.6 Hz, 1H),
1.84–1.68 (m, 4H), 1.48–1.35 (m, 3H), 1.29–1.23 (m, 4H), 0.80 (s,
3H). 13C NMR (150 MHz, CDCl3): d = 205.1, 156.3, 138.3, 133.9,
129.0, 128.9, 127.5, 116.7, 109.6, 68.9, 63.3, 55.7, 45.8, 45.3, 39.8,
39.4, 29.3, 26.5, 26.3, 24.7, 21.3, 19.3, 14.7. HRMS: [M + 1+] calcd
for C23H31O2: 339.2321; found: 339.2325.
2.2.7. Methyl 1-allyloxy-4-methyl-1,3,5(10)-estratriene-17b–
carboxylate (9)
To a stirred suspension of sodium hydride (0.177 g, 7.4 mmol of
a 60% dispersion in mineral oil) in DMF (25 mL) at 0 °C was added a
solution of 8 (0.605 g, 1.8 mmol) in DMF (10 mL), and the reaction
mixture was stirred at 10 °C for 3 h. The reaction solution was
again cooled to 0 °C, allyl bromide (0.500 g, 4.1 mmol) was added,
and the stirring was continued at room temperature for 12 h. The
mixture was then poured into ice water (200 mL), and the aqueous
layer was extracted with ethyl acetate (3 Â 100 mL). The organic
phase was washed, dried and concentrated in vacuo. The residue
was flash-chromatographed (5–10% ethyl acetate in petroleum
ether) to give 9. Yield: 0.625 g (92%). IR (KBr): 3080, 2925, 1726,
2.2.10. 1-Allyloxy-19-nor-4-methylpregna-1,3,5(10),20-tetraene(12)
To a stirred suspension of methyltriphenylphosponium bro-
mide (0.533 g, 1.5 mmol) in THF (10 mL) was added dropwise
n-BuLi (0.6 mL, 1.5 mmol) at À78 °C under argon. The reaction
mixture was warmed to 0 °C and stirred for 1 h. The reaction mix-
ture was again cooled to À78 °C, a solution of 11 (0.350 g,
1.1 mmol) in THF (8 mL) was added dropwise, and the stirring
was continued at 0 °C for 6 h. The reaction was quenched by of sat-
urated aqueous ammonium chloride at 0 °C, and the mixture was
diluted with ethyl acetate (50 mL). The phase were separated, the
aqueous layer was extracted with ethyl acetate (3 Â 20 mL). The
organic phase was washed, dried and concentrated in vacuo. The
residue was flash-chromatographed (5–10% ethyl acetate in petro-
leum ether) to give 12. Yield:0.289 g (83%). IR (KBr): 3082, 2950,
1581, 1516, 1467, 1449, 1437, 1215 cmÀ1 1H NMR (600 MHz,
.
CDCl3): d = 6.93 (d, J = 8.4 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 6.06
(m, 1H), 5.42 (dd, J = 17.4, 1.8 Hz, 1H), 5.26 (dd, J = 10.8, 1.8 Hz,
1H), 4.50 (m, 2H), 3.68 (s, 3H), 3.08 (dd, J = 13.8, 3.6 Hz, 1H),
2.67–2.57 (m, 2H), 2.5–2.54 (m, 2H), 2.20 (m, 1H), 2.16 (s, 3H),
2.02 (dt, J = 13.2, 3 Hz, 1H), 1.85–1.82 (m, 3H), 1.55 (dd, J = 13.2,
3.6 Hz, 1H), 1.50–1.39 (m, 3H), 1.26–1.17 (m, 2H), 0.73 (s, 3H).
13C NMR (150 MHz, CDCl3): d = 174.9, 156.4, 138.4, 133.9, 129.3,
128.9, 127.4, 116.7, 109.6, 68.9, 55.6, 55.3, 51.4, 45.3, 45.1, 40.5,
39.5, 29.4, 26.8, 26.3, 24.4, 23.9, 19.3, 14.3. HRMS: [M+] calcd for
1646, 1586, 1464,1260 cmÀ1 1H NMR (600 MHz, CDCl3): d = 6.91
.
(d, J = 7.8 Hz, 1H), 6.60 (d, J = 7.8 Hz, 1H), 6.03 (m, 1H), 5.80 (m,
1H), 5.39 (dd, J = 17.4, 1.8 Hz, 1H), 5.23 (dd, J = 10.8, 1.8 Hz, 1H),
5.0–4.97 (m, 2H), 4.47 (m, 2H), 3.02 (dd, J = 10.8, 3.0 Hz,
1H), 2.64–2.59 (m, 2H), 2.46 (t, J = 12, 1H), 2.16 (s,3H),2.03
(m, 1H), 1.84–1.79 (m, 2H), 1.77–1.69 (m, 1H), 1.60–1.58 (m,
1H), 1.46–1.18 (m, 7H), 0.66 (s, 3H). 13C NMR (150 MHz, CDCl3):
d = 156.4, 140.2, 138.6, 134.0, 129.6, 128.9, 127.3, 116.6, 114.6,
109.6, 68.9, 55.7, 55.0, 45.6, 44.7, 40.4, 38.5, 29.5, 27.5, 26.6,
26.4, 24.6, 19.4, 13.7. HRMS: [M+] calcd for C24H32O: 336.2453;
found: 336.2449.
C24H32O3: 368.2351; found: 368.2353.
2.2.8. 1-Allyloxy-4-methyl-17b-hydroxymethyl-1,3,5(10)-estratriene
(10)
To a stirred suspension of lithium aluminum hydride (0.077 g,
2.0 mmol) in THF(10 mL) was added dropwise a solution of 9
(0.500 g, 1.4 mmol) in THF (10 mL) at 0 °C under argon, and the
reaction mixture was stirred at room temperature for 24 h. The
reaction mixture was cooled 0 °C, and the reaction was carefully
quenched with water (0.5 mL), 15% aqueous potassium hydroxide
(0.5 mL), and water (1.5 mL). After being stirred for 45 min, the
mixture was diluted with ethyl acetate (50 mL), filtered, and con-
centrated in vacuo. The residue was flash-chromatographed (20–
40% ethyl acetate in petroleum ether) to give 10 as a white solid.
Yield: 0.397 g (86%); m.p. 110–111.5 °C. IR (KBr): 3389, 2935,
2.2.11. 19-nor-4-Methylpregna-1,3,5 (10), 20-tetraen-1-ol
(Krempenes B (1))
To a stirred solution of 12 (0.110 g, 0.3 mmol) in methanol
(10 mL) is added 5% Pd/C (0.52 g) and p-toluenesulfonic acid
(0.025 g, 0.1 mmol). The reaction mixture was refluxed for 72 h.
After removal of the catalyst by filtration, the filtration was con-
centrated in vacuo. The resulting residue was flash-chromato-
graphed (20% ethyl acetate in petroleum ether) to give 1 as a
white crystalline solid. Yield: 0.087 g (90%); m.p. 148.5–150 °C.
1649, 1584, 1474, 1257 cmÀ1 1H NMR (600 MHz, CDCl3): d = 6.93
.
(d, J = 7.8 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 6.06 (m, 1H), 5.42 (dd,
J = 17.4, 1.8 Hz, 1H), 5.25 (dd, J = 10.8, 1.8 Hz, 1H), 4.51 (m, 2H),
3.77 (m, 1H), 3.60 (m, 1H), 3.04 (dd, J = 13.2, 3.6 Hz, 1H), 2.68–
2.58 (m, 2H), 2.49 (t, J = 10.2, 1H), 2.17 (s, 3H), 1.91–1.90 (m,
2H), 1.85–1.73 (m, 3H), 1.49–1.43 (m, 4H), 1.33–1.20 (m, 3H),
0.72 (s, 3H). 13C (150 MHz, CDCl3): d = 156.3, 138.5, 133.9, 129.5,
128.8, 127.3, 116.6, 109.5, 68.9, 64.9, 55.3, 53.4, 45.5, 43.0, 40.0,
39.8, 29.4, 26.7, 26.3, 25.8, 24.4, 19.3, 13.3. HRMS: [M + 1+] calcd
for C23H33O2: 341.2480; found: 341.2476.
[a]
25 = + 82.9 (c = 0.7, CH3OH).
D
IR (KBr): 3493, 3072, 2923, 2856, 1635, 1590,1457, 1270, 1159,
1109 cmÀ1 1H NMR (600 MHz, CDCl3): d = 6.84 (d, J = 7.8 Hz, 1H),
.
6.47 (d, J = 7.8 Hz, 1H), 5.82 (ddd, J = 7.8, 11.4, 18 Hz, 1H), 5.01
(dd, J = 17.4, 1.8 Hz, 1H), 4.99 (dd, J = 10.8, 1.8 Hz, 1H), 4.56 (broad
s, 1H), 2.97 (dddd, J = 16.2, 4.2, 4.2, 3.6 Hz, 1H), 2.65 (ddd, J = 16.8,
16.2, 4.2, 1H),2.59 (ddd, J = 12, 12, 5.4 Hz, 1H), 2.43 (dd, J = 10.8,
10.2 Hz, 1H), 2.15 (s, 3H), 2.08 (ddd, J = 9, 9, 8.4 Hz, 1H), 1.84–
1.80 (m, 2H), 1.77–1.74 (m, 1H), 1.72 (ddd, J = 13.8, 3.6, 3.6 Hz
1H), 1.60–1.57 (m, 1H), 1.45(dddd, J = 12, 10.8, 10.2, 1.8 Hz, 1H),
1.35 (ddd, J = 12, 10.8, 6 Hz, 1H), 1.34–1.32 (m, 1H),1.28 (dd,
J = 12.0, 10.8, Hz, 1H), 1.21(dddd, J = 16.2, 4.2, 4.2, 3.6 Hz, 1H),
1.22–1.18 (m, 1H), 0.67 (s, 3H). 13C NMR(150 MHz, CDCl3):
d = 153.1, 140.1, 138.8, 128.8, 127.6, 127.2, 114.6, 113.0, 55.7,
55.0, 45.3, 44.6, 40.3, 38.5, 29.4, 27.5, 26.5, 26.2, 24.7, 19.4, 13.6.
HRMS: [M+] calcd for C21H28O: 296.2140; found: 296.2134.
2.2.9. 1-Allyloxy-4-methyl-17b-formyl-1,3,5(10)-estratriene (11)
To a stirred solution of 10 (0.200 g, 0.6 mmol) in dichlorometh-
ane (20 mL) was added Dess-Martin periodinane (0.750 g,
1.8 mmol) at room temperature. After 45 min, saturated aqueous
NaHCO3 (5 mL) and 10% Na2S2O3 (5 mL) were added to the reaction
mixture, and the aqueous layer was extracted with dichlorometh-
ane (3 Â 20 mL). The organic phase was washed with 10 mL of 1:1
10% Na2S2O3: saturated aqueous NaHCO3, followed by 10 mL of