356
steroids 7 2 ( 2 0 0 7 ) 351–359
gave product 15b (150 mg, 41%) as a solid: 1H NMR (CDCl3) ı
0.90 (s, 3H, C18–CH3), 2.87–2.89 (m, 2H, C6–CH2), 3.80 (s, 3H,
OCH3), 5.21 (d, J = 6 Hz, C17–H), 6.15 (m, 1H, C11–H), 6.62 (d, 1H,
J = 2.7 Hz, C4–H), 6.72 (dd, 1H, J = 8.7 Hz, 2.7 Hz, C2–H), 7.55 (d,
1H, J = 8.7 Hz, C1–H), 8.18–8.31 (m, 4H, Ar–H).
purified by chromatography (35% EtOAc in hexanes) and crys-
tallized from CH2Cl2/hexanes to give product 14a (70 mg, 61%)
25
as white crystals: mp 191–192 ◦C; lit [31] mp 186–191 ◦C; [␣]d
−138.4 (c = 0.31, dioxane), UV (EtOH) ꢀmax 265 nm (ε = 11,900);
IR (KBr, cm−1) 3421, 1630, 1614, 1578, 1287, 1246, 1055; 1H
NMR (CDCl3/acetone-d6) ı 0.81 (s, 3H, C18–CH3), 2.77–2.82 (m,
2H, C6–CH2), 3.35 (d, 1H, J = 5.1 Hz, C8–H), 3.80 (m, 1H, C17–H),
6.08 (d, 1H, J = 5.1 Hz, C11–H), 6.56 (d, 1H, J = 2.7 Hz, C4–H), 6.65
(dd, 1H, J = 8.7 Hz, 2.7 Hz, C2–H), 7.45 (d, J = 8.7 Hz, C1–H); 13C
NMR (CDCl3/acetone-d6) ı 155.28, 130.92, 134.67, 125.97, 124.55,
116.25, 114.44, 113.16, 80.82, 46.79, 40.87, 38.39, 38.30, 29.83,
28.29, 27.59, 23.20, 10.18; MS m/z: 270 (M+), 211, 181, 169, 157,
149, 129, 111, 97, 83.69.
2.1.21. (8˛,9ˇ,13˛,14ˇ,17ˇ)-3-Methoxyestra-1,3,5(10)-
trien-17-ol (16a)
Compound 15a (70 mg, 0.16 mmol) dissolved in THF (2 ml) was
stirred with 2.8% methanolic KOH (3 ml) at room temperature
for 2 h. Solvent removal and chromatography (15% EtOAc in
hexanes) gave product 16a (40 mg, 87%): 1H NMR (CDCl3) ı 0.70
(s, 3H, C18–CH3), 2.84–2.87 (m, 2H, C6–CH2), 3.78 (s, 3H, OCH3),
3.82 (m, 1H, C17–H), 6.64 (d, 1H, C4–H), 6.72 (dd, J = 8.7 Hz, 2.7 Hz,
C2–H), 7.23 (d, J = 8.7 Hz, C1–H); 13C NMR (CDCl3) ı 157.57, 138.17,
132.87, 126.45, 113.88, 111.53, 80.08, 55.16, 47.71, 45.51, 43.55,
39.03, 32.36, 31.41, 29.84, 27.99, 26.14, 24.18, 16.96.
2.1.18. (13˛,14ˇ,17˛)-Estra-1,3,5(10),8-tetraene-3,17-diol
(14b)
A solution of compound 13b (70 mg, 0.25 mmol) in anhy-
drous toluene (3 ml) under N2 was added to DIBALH (1.5 M
in toluene, 1.5 ml, 2.25 mmol). The reaction was refluxed
overnight, cooled to room temperature and ice was added.
The reaction mixture was then acidified with 2.5N HCl and
extracted with EtOAc. The combined extracts were washed
with brine and dried. Solvent removal gave a pale yellow oil
(80 mg), which was purified by chromatography (30% EtOAc
in hexanes) to give product 14b (40 mg, 60%) as an oil, which
later solidified to a red orange solid that could not be further
purified. Product 14b had: mp 86–96 ◦C; lit [31] mp 130–132 ◦C;
2.1.22. (8˛,13˛,14ˇ,17ˇ)-3-Methoxyestra-1,3,5(10),9(11)-
tetraen-17-ol (16b)
Compound 15b (150 mg, 0.35 mmol) dissolved in THF (4 ml)
was stirred with 3% methanolic KOH (6 ml) at room temper-
ature for 1 h. After acidification with 3N HCl, and solvent
removal, the residue was chromatographed (20% EtOAc in hex-
anes) to give product 16b (60 mg, 61%) as a solid: 1H NMR
(CDCl3) ı 0.71 (s, 3H, C18–CH3), 2.82–2.84 (m, 2H, C6–CH2), 3.78
(s, 3H, OCH3), 3.84–3.86 (d, 1H, J = 5.1 Hz, C17–H), 6.17 (t, 1H,
J = 2.7 Hz, C11–H), 6.60 (d, 1H, J = 2.4 Hz, C4–H), 6.71 (dd, 1H,
J = 8.7 Hz, 2.4 Hz, C2–H), 7.54 (d, 1H, J = 8.7 Hz, C1–H). 13C NMR
(CDCl3) ı 158.31, 137.55, 134.79, 127.66, 125.15, 117.90, 113.27,
112.63, 79.49, 55.13, 45.43, 43.89, 38.98, 33.08, 32.66, 30.09, 29.09,
24.92, 17.37.
25
[␣]d −99.5 (c = 0.37, CHCl3), UV (EtOH) ꢀmax 273 nm (ε = 16,200);
IR (KBr, cm−1) 3447, 1678, 1649, 1615, 1260, 1194, 1098; 1H NMR
(CDCl3) ı 1.00 (s, 3H, C18–CH3), 2.68 (t, J = 7.6 Hz, 2H, C6–CH2),
3.86 (t, J = 5.4 Hz, 1H, C17–H), 5.83 (s, OH), 6.61 (s, 1H, C4–H), 6.64
(dd, J = 2.7 Hz, 8.1 Hz, 1H, C2–H), 7.06 (d, J = 8.1 Hz, 1H, C1–H);
13C NMR (CDCl3) ı 153.87, 137.27, 134.28, 129.30, 123.82, 122.97,
114.52, 112.59, 80.86, 48.09, 43.56, 32.17, 29.63, 29.16, 28.72,
28.24, 22.24, 18.49; MS m/z 270 (M+), 237, 227, 211, 197, 181,
172, 157, 145, 137, 129, 111, 97, 81, 69.
2.1.23. (8˛,9ˇ,13˛,14ˇ,17ˇ)-Estra-1,3,5(10)-triene-3,17-
diol (17a)
A solution of compound 16a (40 mg, 0.14 mmol) in anhy-
drous toluene (3 ml) under N2 was added to DIBALH (1.5 M
in toluene, 1.5 ml, 2.25 mmol). The reaction was refluxed
overnight, cooled to room temperature and ice was added. The
reaction mixture was then acidified with 3N HCl and extracted
with EtOAc. The combined extracts were washed with brine
and dried. Solvent removal, chromatography (20% EtOAc in
hexanes) and recrystallization from acetone/hexanes gave
2.1.19. (8˛,9ˇ,13˛,14ˇ,17ˇ)-3-Methoxyestra-1,3,5(10)-
trien-17-ol p-nitrobenzoate (15a)
The mixture of compound 10 (80 mg, 0.28 mmol), p-
nitrobenzoic acid (0.12 g, 0.72 mmol), triphenylphosphine
(0.15 g, 0.57 mmol) and diethylazodicarboxylate (0.13 g,
0.75 mmol) in anhydrous toluene (2 ml) was heated at 80 ◦C
for 3.5 h. Solvent removal followed by chromatography (10%
EtOAc in hexanes) gave product 15a (70 mg, 58%) as a solid:
1H NMR (CDCl3) ı 0.79 (s, 3H, C18–CH3), 2.80 (m, 2H, C6–CH2),
3.69 (s, 3H, OCH3) 5.07 (d, 1H, J = 6 Hz, C17–H), 6.56 (d, 1H,
J = 2.4 Hz, C4–H), 6.62 (dd, J = 8.7 Hz, 2.7 Hz, C2–H), 7.11 (d, 1H,
J = 8.7 Hz, C1–H), 8.12–8.23 (m, 4H, Ar–H); 13C NMR (CDCl3) ı
164.34, 157.60, 150.55, 137.93, 136.25, 132.35, 130.68, 126.39,
123.59, 113.84, 111.54, 83.82, 55.09, 49.49, 45.39, 43.54, 38.96,
32.08, 30.09, 29.74, 27.94, 25.98, 24.29, 16.60.
product 17a (30 mg, 79%): mp 224–225 ◦C; [␣]d −54.9 (c = 0.40,
22
dioxane); IR (KBr, cm−1) 3421, 1611, 1587, 1252, 1234, 1035; 1H
NMR (CDCl3/acetone-d6) ı 0.70 (s, 3H, C18–CH3), 2.77–2.78 (m,
2H, C6–CH2), 3.75 (q, J = 6 Hz, 1H, C17–H), 6.54 (d, 1H, J = 2.4 Hz,
C4–H), 6.59 (dd, 1H, J = 8.4 Hz, 2.4 Hz, C2–H), 7.10 (d, 1H, J = 8.4 Hz,
C1–H); 13C NMR (CDCl3/acetone-d6) ı 154.02, 136.72, 130.50,
125.29, 114.18, 111.78, 78.14, 46.51, 44.39, 42.72, 38.30, 31.18,
30.53, 29.01, 27.12, 25.27, 23.08, 15.77. Anal. Calcd. for C18H24O2:
C, 79.37; H, 8.88. Found: C, 79.18; H, 8.62.
2.1.20. (8˛,13˛,14ˇ,17ˇ)-3-Methoxyestra-1,3,5(10),9(11)-
tetraen-17-ol p-nitrobenzoate (15b)
2.1.24. (8˛,13˛,14ˇ,17ˇ)-Estra-1,3,5(10),9(11)-tetraene-
3,17-diol (17b)
A mixture of compound 13a (0.24 g, 0.85 mmol), p-nitrobenzoic
acid (305 mg, 1.84 mmol), triphenylphosphine (0.49 g,
1.87 mmol) and diethylazodicarboxylate (0.45 g, 2.58 mmol)
in anhydrous toluene (7 ml) was heated at 80 ◦C for 6 h.
Solvent removal and chromatography (10% EtOAc in hexanes)
A solution of compound 16b (60 mg, 0.21 mmol) in anhy-
drous toluene (3 ml) under N2 was added to DIBALH (1.5 M
in toluene, 1.5 ml, 2.25 mmol). The reaction was refluxed
overnight, cooled to room temperature and ice was added.
The reaction mixture was then acidified with 3N HCl and