146
steroids 7 1 ( 2 0 0 6 ) 141–153
celite. After evaporation of the filtrate, the crude product was
purified by column chromatography with ethyl acetate/CHCl3
10:90).
(s, 2H, benzyl-H2), 6.71 (d, 1H, J = 2.3 Hz, 4-H), 6.77 (dd, 1H,
J = 8.6 Hz, J = 2.3 Hz, 2-H), 7.18 (d, 1H, J = 8.6 Hz, 1-H), 7.30 (t,
1H, J = 7.3 Hz, 4ꢀ-H), 7.36 (t, 2H, J = 7.3 Hz, 3ꢀ,5ꢀ-H), 7.41 (d, 2H,
J = 7.3 Hz, 2ꢀ,6ꢀ-H). 13C NMR (CDCl3) ı, ppm: 12.3 (C-18), 26.2,
27.4, 29.7, 32.6, 36.4, 37.6, 38.1, 43.3, 43.9, 44.5 (C-13), 48.2, 70.0
(benzyl-CH2), 81.9 (C-17), 112.4 (C-2), 114.9 (C-4), 126.2 (C-1);
127.4 (2C, C-2ꢀ,6ꢀ), 127.8 (C-4ꢀ), 128.5 (2C, C-3ꢀ,5ꢀ), 132.8 (C-10),
137.4 (C-1ꢀ), 137.9 (C-5), 156.8 (C-3); EI-MS (70 eV) m/z (%): 456
(42) [M+ + 2], 454 (41) [M+], 91 (100).
5e (542 mg, 96%). Mp 168–169 ◦C; Rf = 0.40 (ss B); [˛]D20 + 114
(c 1.00 in ethyl acetate). (Found: C, 62.55; H, 7.02. C19H25O2Br
requires: C 62.47; H 6.90%). 1H NMR (DMSO-d6) ␦, ppm: 0.68
(s, 3H, 18-H3), 2.70 (m, 2H, 6-H2), 3.28 (t, 1H, J = 10.9 Hz, 17-H),
3.63 (m, 1H) and 3.76 (dd, 1H, J = 9.6 Hz, J = 4.2 Hz): 16a-H2, 4.84
(d, 1H, J = 5.5 Hz, 17-OH), 6.43 (s, 1H, 4-H), 6.50 (d, 1H, J = 7.9 Hz,
2-H), 7.02 (d, 1H, J = 8.5 Hz, 1-H), 8.96 (s, 1H, 3-OH). 13C NMR
(DMSO-d6) ␦, ppm: 12.4 (C-18), 25.9, 27.0, 29.1, 32.4, 37.1, 37.9,
39.3, 43.1, 43.4, 43.8, 47.4, 80.6 (C-17), 112.7 (C-2), 114.9 (C-4),
125.9 (C-1); 130.3 (C-10), 137.0 (C-5), 154.8 (C-3); EI-MS (70 eV)
m/z (%): 366 (34) [M+ + 2], 364 (36) [M+], 267 (23), 213 (12), 185 (9),
159 (17), 145 (10), 133 (24), 83 (11), 43 (100).
6a (1.16 g, 85%). Mp 119–120 ◦C; Rf = 0.80 (ss A); [˛]D20 + 89 (c
1.00 in CHCl3). (Found: C, 68.67; H, 6.79. C26H31O2Br requires:
C, 68.57; H, 6.86%). 1H NMR (CDCl3) ı, ppm: 0.78 (s, 3H, 18-H3),
2.83 (m, 2H, 6-H2), 3.48 (dd, 1H, J = 9.4 Hz, J = 6.5 Hz) and 3.61 (t,
1H, J = 9.4 Hz): 16a-H2, 3.85 (t, 1H, J = 4.4 Hz, 17-H), 5.02 (s, 2H,
benzyl-H2), 6.70 (d, 1H, J = 2.5 Hz, 4-H), 6.77 (dd, 1H, J = 8.5 Hz,
J = 2.5 Hz, 2-H), 7.19 (d, 1H, J = 8.5 Hz, 1-H), 7.30 (t, 1H, J = 7.3 Hz,
4ꢀ-H), 7.36 (t, 2H, J = 7.3 Hz, 3ꢀ,5ꢀ-H), 7.41 (d, 2H, J = 7.3 Hz, 2ꢀ,6ꢀ-
H). 13C NMR (CDCl3) ı, ppm: 17.2 (C-18), 26.0, 27.9, 29.8, 31.1,
31.2, 34.9 (C-16a), 39.0, 43.5, 44.0, 46.3 (C-13), 47.3, 70.0 (benzyl-
CH2), 79.9 (C-17), 112.3 (C-2), 114.9 (C-4), 126.3 (C-1); 127.4 (2C,
C-2ꢀ,6ꢀ), 127.8 (C-4ꢀ), 128.5 (2C, C-3ꢀ,5ꢀ), 132.9 (C-10), 137.4 (C-1ꢀ),
137.9 (C-5), 156.8 (C-3); EI-MS (70 eV) m/z (%): 456 (23) [M+ + 2],
454 (23) [M+], 91 (100).
6e (550 mg, 98%). Mp 181–183 ◦C; Rf = 0.50 (ss B); [˛]D20 + 70
(c 1.00 in ethyl acetate). (Found: C, 62.55; H, 7.02. C19H25O2Br
requires: C 62.47; H 6.90%). 1H NMR (DMSO-d6) ı, ppm: 0.68 (s,
3H, 18-H3), 2.70 (m, 2H, 6-H2), 3.41 (t, 1H, J = 8.6 Hz) and 3.63
(t, 1H, J = 8.6 Hz): 16a-H2, 3.60 (d, 1H, J = 5.0 Hz, 17-H), 6.43 (d,
1H, J = 2.0 Hz, 4-H), 6.50 (dd, 1H, J = 8.4 Hz, J = 2.0 Hz, 2-H), 7.04
(d, 1H, J = 8.4 Hz, 1-H), 8.96 (s, 1H, 3-OH). 13C NMR (DMSO-d6)
ı, ppm: 17.0 (C-18), 25.8, 27.6, 29.2, 30.6, 31.2, 36.7, 38.8, 43.2,
43.6, 46.1, 46.3, 78.5 (C-17), 112.7 (C-2), 114.8 (C-4), 125.9 (C-1);
130.4 (C-10), 137.1 (C-5), 154.8 (C-3); EI-MS (70 eV) m/z (%): 366
(99) [M+ + 2], 364 (100) [M+], 267 (15), 213 (21), 198 (15), 185 (11),
172 (22), 159 (35), 146 (20), 133 (37), 107 (13).
7e (547 mg, 97%). Mp 188–189 ◦C; Rf = 0.30 (ss B); [˛]D20 + 37
(c 1.00 in ethyl acetate). (Found: C, 62.36; H, 6.84. C19H25O2Br
requires: C 62.47; H 6.90%). 1H NMR (DMSO-d6) ı, ppm: 0.71 (s,
3H, 18-H3), 2.70 (m, 2H, 6-H2), 3.24 (m, 1H, 17-H), 3.55 (t, 1H,
J = 9.6 Hz) and 3.73 (dd, 1H, J = 9.6 Hz, J = 3.4 Hz): 16a-H2, 4.87 (d,
1H, J = 4.8 Hz, 17-OH), 6.43 (s, 1H, 4-H), 6.50 (d, 1H, J = 8.4 Hz,
2-H), 7.01 (d, 1H, J = 8.4 Hz, 1-H), 9.00 (s, 1H, 3-OH). 13C NMR
(DMSO-d6) ı, ppm: 12.0 (C-18), 25.9, 26.8, 28.9, 29.1, 36.5, 38.3,
40.6, 43.4, 44.0, 45.6, 47.7, 83.4 (C-17), 112.7 (C-2), 114.9 (C-4),
125.9 (C-1); 130.3 (C-10), 137.1 (C-5), 154.8 (C-3); EI-MS (70 eV)
m/z (%): 366 (87) [M+ + 2], 364 (89) [M+], 267 (31), 213 (34), 198
(43), 185 (32), 172 (72), 159 (89), 145 (44), 133 (100), 107 (27), 43
(19).
8e (540 mg, 96%). Mp 186–188 ◦C; Rf 0.30 (ss B); [˛]D20 + 61
(c 1.00 in ethyl acetate). (Found: C, 62.55; H, 7.08. C19H25O2Br
requires: C 62.47, H 6.90%). 1H NMR (DMSO-d6) ı, ppm: 0.67 (s,
3H, 18-H3), 2.69 (m, 2H, 6-H2), 3.38 (d, 1H, J = 4.2 Hz, 17-H), 3.50
(t, 1H, J = 9.2 Hz) and 3.66 (t, 1H, J = 9.2 Hz): 16a-H2, 4.67 (d, 1H,
J = 4.6 Hz, 17-OH), 6.43 (s, 1H, 4-H), 6.50 (d, 1H, J = 8.4 Hz, 2-H),
7.03 (d, 1H, J = 8.4 Hz, 1-H), 8.95 (s, 1H, 3-OH). 13C NMR (DMSO-
d6) ı, ppm: 17.8 (C-18), 25.8, 27.7, 29.2, 31.6, 32.0, 38.4, 38.9, 43.0,
44.6, 48.7, 51.7, 82.6 (C-17), 112.7 (C-2), 114.9 (C-4), 125.9 (C-1);
130.4 (C-10), 137.0 (C-5), 154.8 (C-3); EI-MS (70 eV) m/z (%): 366
(100) [M+ + 2], 364 (98) [M+], 267 (23), 213 (17), 198 (11), 172 (18),
159 (21), 146 (12), 133 (23).
7a (1.08 g, 79%). Mp 90–91 ◦C; Rf = 0.30 (ss A); [˛]2D0 + 50 (c 1.00
in CHCl3). (Found: C, 68.63; H, 6.95. C26H31O2Br requires: C,
68.57; H, 6.86%). 1H NMR (CDCl3) ı, ppm: 0.83 (s, 3H, 18-H3), 2.84
(m, 2H, 6-H2), 3.47 (d, 1H, J = 7.6 Hz, 17-H), 3.54–3.61 (overlap-
ping multiplets, 2H, 16a-H2, 5.02 (s, 2H, benzyl-H2), 6.71 (d, 1H,
J = 2.3 Hz, 4-H), 6.77 (dd, 1H, J = 8.6 Hz, J = 2.3 Hz, 2-H), 7.18 (d, 1H,
J = 8.6 Hz, 1-H), 7.30 (t, 1H, J = 7.3 Hz, 4ꢀ-H), 7.36 (t, 2H, J = 7.3 Hz,
3ꢀ,5ꢀ-H), 7.41 (d, 2H, J = 7.3 Hz, 2ꢀ,6ꢀ-H). 13C NMR (CDCl3) ı, ppm:
12.0 (C-18), 26.1, 27.2, 29.7, 29.8, 36.6, 38.3, 38.9 (C-16a), 43.9,
44.6 (C-13), 45.8, 48.3, 69.9 (benzyl-CH2), 85.8 (C-17), 112.3 (C-
2), 114.8 (C-4), 126.2 (C-1); 127.4 (2C, C-2ꢀ,6ꢀ), 127.8 (C-4ꢀ), 128.5
(2C, C-3ꢀ,5ꢀ), 132.7 (C-10), 137.3 (C-1ꢀ), 137.9 (C-5), 156.7 (C-3);
EI-MS (70 eV) m/z (%): 456 (24) [M+ + 2], 454 (25) [M+], 91 (100).
8a (1.09 g, 80%). Mp 51–53 ◦C; Rf = 0.35 (ss A); [˛]2D0 + 35 (c 1.00
in CHCl3). (Found: C, 68.62; H, 6.94. C26H31O2Br requires: C,
68.57; H, 6.86%. 1H NMR (CDCl3) ı, ppm: 0.76 (s, 3H, 18-H3),
2.84 (m, 2H, 6-H2), 3.51 (m, 2H, 16a-H2),), 3.64 (s, 1H, 17-H),
5.02 (s, 2H, benzyl-H2), 6.71 (d, 1H, J = 2.4 Hz, 4-H), 6.77 (dd,
1H, J = 8.6 Hz, J = 2.4 Hz, 2-H), 7.19 (d, 1H, J = 8.6 Hz, 1-H), 7.30
(t, 1H, J = 7.3 Hz, 4ꢀ-H), 7.36 (t, 2H, J = 7.3 Hz, 3ꢀ,5ꢀ-H), 7.41 (d, 2H,
J = 7.3 Hz, 2ꢀ,6ꢀ-H). 13C NMR (CDCl3) ı, ppm: 17.9 (C-18), 25.9,
27.9, 29.7, 31.9, 32.1, 37.3 (C-16a), 38.6, 43.3, 45.1 (C-13), 49.3,
52.2, 70.0 (benzyl-CH2), 84.1 (C-17), 112.3 (C-2), 114.9 (C-4), 126.2
(C-1); 127.4 (2C, C-2ꢀ,6ꢀ), 127.8 (C-4ꢀ), 128.5 (2C, C-3ꢀ,5ꢀ), 132.8 (C-
10), 137.3 (C-1ꢀ), 137.9 (C-5), 156.8 (C-3); EI-MS (70 eV) m/z (%):
456 (6) [M+ + 2], 454 (6) [M+], 91 (100).
2.4.
Debenzylation of 3-benzyloxy-16-
bromomethylestra-1,3,5(10)-trien-17-ol isomers (5a–8a)
with Pd/C to 16-bromomethylestra-1,3,5(10)-
triene-3,17-diols (5e–8e)
2.5.
Reaction of 3-benzyloxy-16˛-
bromomethylestra-1,3,5(10)-trien-17ˇ-ol (7a)
2.4.1. General procedure
with HBr in acetic acid
Compounds 5a–7a or 8a (700 mg, 1.54 mmol) was dissolved
in 50 ml of ethyl acetate and 250 mg of Pd/C was added to
the solution, which was stirred at room temperature for 6 h
at 30 bar H2 pressure. The reaction mixture was filtered over
2.5.1. Method B
2.5.1.1. 16˛-Bromomethyl-3-hydroxyestra-1,3,5(10)-trien-17ˇ-
yl acetate (7c). Compound 7c (950 mg, 78%). Mp 181–182 ◦C,