M. Teranishi et al. / Steroids 66 (2001) 615–621
617
7␣-H), 2.37 (3H, s, 4-OCOCH3), 2.69 (1H, dd, J ϭ 17.1, 3.5
2.7. 3-Benzyloxy-4-methoxy-1,3,5(10)-estratrien-17-one
(8)
Hz, 7-H), 3.86–3.98 (4H, m, -OCH2CH2O-), 5.10 (2H, s,
3-OCH2C6H5), 7.13 (1H, d, J ϭ 8.8 Hz, 2-H), 7.21 (1H, d,
J ϭ 8.8Hz, 1-H), 7.28–7.38 (5H, m, 3-OCH2C6H5). MS
m/z: 476 (Mϩ), 434 ([M-AcϩH]ϩ), 343 ([M-AcϩH-
C6H5CH2]ϩ), 91 (C6H5CH2ϩ). Analysis calculated for
C29H32O6: C, 73.09; H, 6.77. Found: C, 72.93; H, 6.69.
30% KOH solution (0.5 ml) was added slowly to a stirred
solution of 7 (78.7 mg) in MeOH (10 ml) containing di-
methyl sulfate (0.4 ml) at 0°C, and the mixture was heated
at 40°C for 10 h. After most of the MeOH was evaporated
under reduced pressure, the reaction mixture was extracted
with CHCl3, washed with water, and dried over anhydrous
Na2SO4. After evaporation of the solvent, the crude product
obtained was recrystallized from MeOH to give 8 (77.5 mg,
95%) as colorless needles. mp 116.5–117.0°C. (Reported
mp 117–118°C [9]). 1H-NMR ␦: 0.90 (3H, s, 18-CH3), 2.73
(1H, m, 6-H), 3.05 (1H, dd, J ϭ 17.8, 5.3 Hz, 6␣-H), 3.86
(3H, s, 4-OCH3), 5.10 (2H, s, 3-OCH2C6H5), 6.80 (1H, d,
J ϭ 8.6 Hz, 2-H), 6.96 (1H, d, J ϭ 8.6 Hz, 1-H), 7.28–7.47
(5H, m, 3-OCH2C6H5). MS m/z: 390 (Mϩ), 299 ([M-
C6H5CH2]ϩ), 91 (C6H5CH2ϩ).
2.5. 3-Benzyloxy-17,17-ethylenedioxy-1,3,5 (10)-
estratrien-4-ol (6)
Sodium borohydride (175 mg) was added to a solution of
5 (108 mg) in MeOH (50 ml), and the mixture was stirred
at room temperature for 30 min. Excess reagent was de-
stroyed by addition of a few drops of AcOH, and MeOH
was removed under reduced pressure. The reaction mixture
was extracted with CHCl3, washed with water, and dried
over anhydrous Na2SO4. After evaporation of the solvent,
the crude product obtained was recrystallized from MeOH
to give 6 (79.3 mg, 83%) as colorless rods. mp 137.4–
138.5°C. [␣]2D7 ϩ17.7° (c ϭ 0.44). UV max (EtOH) nm (⑀):
2.8. 3-Hydroxy-4-methoxy-1,3,5(10)-estratrien-17-one (9)
279 (2350). IR
(KBr) cmϪ1: 3458 (OH), 1493 (aro-
max
A solution of 8 (52.0 mg) in EtOH (50 ml) was shaken
with 5% palladium-on-carbon (20 mg) under a stream of
hydrogen at room temperature for 7 h. The reaction mixture
was filtered, and the filtrate was concentrated to an oily
residue, which was purified by chromatography on silica gel
using hexane/AcOEt (4:1). The eluate was recrystallized
from MeOH to give 9 (35.8 mg, 90%) as colorless needles.
mp 195.2–206.5°C. 1H-NMR ␦: 0.92 (3H, s, 18-CH3), 2.76
(1H, m, 6-H), 3.02 (1H, dd, J ϭ 17.6, 5.4 Hz, 6␣-H), 3.79
(3H, s, 4-OCH3), 5.52 (1H, s, 3-OH), 6.80 (1H, d, J ϭ 8.6
Hz, 2-H), 6.98 (1H, d, J ϭ 8.6 Hz, 1-H). MS m/z: 300 (Mϩ),
269 ([M-OCH3]ϩ).
1
matic). H-NMR ␦: 0.88 (3H, s, 18-CH3), 2.63 (1H, m,
6-H), 2.93 (1H, dd, J ϭ 17.6, 5.3 Hz, 6␣-H), 3.86–3.98
(4H, m, -OCH2CH2O-), 5.08 (2H, s, 3-OCH2C6H5), 5.71
(1H, s, 4-OH), 6.76 (1H, d, J ϭ 8.6 Hz, 2-H), 6.79 (1H, d,
J ϭ 8.8 Hz, 1-H), 7.32–7.43 (5H, m, 3-OCH2C6H5). 13C-
NMR ␦: 143.2 (s, C-4), 143.1 (s, C-3), 136.8 (s, C1 of Ph),
134.6 (s, C-10), 128.7 (d, C3 and C5 of Ph), 128.2 (d, C4 of
Ph), 127.7 (d, C2 and C6 of Ph), 123.6 (s, C-5), 119.5 (s,
C-17), 116.0 (d, C-1), 109.3 (d, C-2), 71.2 (t, 3-OCH2Ph),
65.2 and 64.6 (t, -OCH2CH2O-), 49.4 (d, C-14), 46.1 (s,
C-13), 43.8 (d, C-9), 38.5 (d, C-8), 34.2 (t, C-16), 30.8 (t,
C-12), 26.5 (t, C-7), 26.2 (t, C-11), 23.3 (t, C-6), 22.4 (t,
C-15), 14.3 (q, C-18). MS m/z: 420 (Mϩ), 329 ([M-
C6H5CH2]ϩ), 91 (C6H5CH2ϩ). Analysis calculated for
C27H32O4: C, 77.11; H, 7.67. Found: C, 77.15; H, 7.65.
2.9. 3,4-Dihydroxy-1,3,5(10)-estratriene-6,17-dione (10)
Solid NaHCO3 (48 mg) and water (3 ml) were added to
a solution of 1 (136 mg) in MeOH (100 ml), and the mixture
was stirred at room temperature for 8 h. The reaction mix-
ture was acidified by adding a few drops of AcOH (0.1 ml),
and most of the MeOH was removed under reduced pres-
sure. The mixture was extracted with CHCl3, washed with
water, and dried over anhydrous Na2SO4. After evaporation
of the solvent, the crude product obtained was recrystallized
from MeOH to give 10 (104 mg, 98%) as colorless needles.
2.6. 3-Benzyloxy-4-hydroxy-1,3,5(10)-estratrien-17-one (7)
5% HCl (3 ml) was added to a solution of 6 (95.2 mg) in
MeOH (20 ml), and the mixture was stirred at room tem-
perature for 1 h. Saturated aqueous NaHCO3 was added to
neutralize the HCl, and most of the MeOH was removed
under reduced pressure. The mixture was extracted with
CHCl3, and the extract was washed with water and dried
over anhydrous Na2SO4. After evaporation of the solvent,
the crude product obtained was recrystallized from MeOH
to give 7 (78.7 mg, 92%) as colorless needles. mp 152.2–
mp 193.4–194.5°C. [␣]2D4 ϩ70.0° (c ϭ 0.53). UV
max
(EtOH) nm (⑀): 272 (9300), 361 (3120). IR
(KBr)
max
cmϪ1: 3435 (OH), 1728, 1631 (C ϭ O), 1439 (aromatic).
1H-NMR ␦: 0.92 (3H, s, 18-CH3), 2.39 (1H, dd, J ϭ 17.2,
12.8 Hz, 7␣-H), 2.85 (1H, dd, J ϭ 17.2, 3.7 Hz, 7-H), 5.74
(1H, s, 3-OH), 6.77 (1H, dd, J ϭ 8.4, 1.3 Hz, 1-H), 7.10
(1H, d, J ϭ 8.4 Hz, 2-H), 12.75 (1H, s, 4-OH). MS m/z: 300
(Mϩ). HRMS Calculated for C18H20O4: 300.1362. Found:
300.1362. Analysis calculated for C18H20O4⅐1/5H2O: C,
71.13; H, 6.77. Found: C, 71.23; H, 6.86.
1
153.0°C. H-NMR ␦: 0.90 (3H, s, 18-CH3), 2.67 (1H, m,
6-H), 2.99 (1H, dd, J ϭ 17.4, 5.3 Hz, 6␣-H), 5.09 (2H, s,
3-OCH2C6H5), 5.76 (1H, s, 4-OH), 6.78 (2H, s, 1-H and
2-H), 7.32–7.43 (5H, m, 3-OCH2C6H5). MS m/z: 376 (Mϩ),
285 ([M-C6H5CH2]ϩ), 91 (C6H5CH2ϩ). The product was
identical in all respects to that (mp 150.5–152.5°C) prepared
by Shimada et al. [14].