916
steroids 7 1 ( 2 0 0 6 ) 911–921
2.8 Hz, 2× 2-CH), 6.72 (2H, s, 2× 4-CH), 5.03 (4H, s, 2× CH2Ph),
3.80–3.50 (16H, s and #m, 8× CH2O), 2.84 (4H, m, 2× 6-CH2),
2.66 (2H, sl, 2× OH), 2.40–1.20 (34H, #m, 14× CH2, 6× CH), 0.92
(6H, s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm): 156.7 (C-3), 138.0
(CCH2O), 137.3 (C-5), 133.0 (C-10), 128.5 (C-b), 127.8 (C-c), 127.4
(C-a), 126.3 (C-1), 114.8 (C-4), 112.2 (C-2), 83.0 (C-17), 72.0, 70.6,
70.5, 70.0, 69.9 (CH2Ph), 49.5, 46.8, 43.8, 39.6, 34.3, 33.4, 31.7,
29.8, 27.5, 26.3, 24.0, 23.4, 14.4 (C-18). MS (m/e): 937 (M+–H2O),
919 (M+–2 H2O), 828 (M+–H2O,–C7H7). Exact mass: calculated
tion of protected dimer 6 (a–e) (R = Bn) (0.07 mmol) dissolved
in dry THF (2.5 mL). Then, hydrogen was bubbled into the
reaction mixture for 3 min and the hydrogenolysis was per-
formed under 1 atmosphere of hydrogen for 24 h at 22 ◦C.
Afterwards, the catalyst was filtered off and the filtrate evap-
orated to give the pure 17-estradiol dimers 6 (a–e) (R = H)
quantitatively.
2.1.2.11. Spectral data for dimer 6a (R = H). IR (NaCl, ꢀmax
,
for C62
H
80O7 (M–H2O) = 936.5904; found = 936.5887.
cm−1): 3372 (O–H), 1609 (C C), 1240 and 1093 (C–O). 1H NMR
(CDCl3, CD3OD, ı ppm): 7.06 (2H, d, J = 8.4 Hz, 2× 1-CH), 6.58
(2H, dd, J = 8.6 Hz and J = 1.6 Hz, 2× 2-CH), 6.52 (2H, s, 2× 4-CH),
3.65–3.40 (12H, #m, 6× CH2O), 3.03 (4H, sl, 3-OH and 17-OH),
2.76 (4H, m, 2× 6-CH2), 2.30–1.15 (34H, #m, 14× CH2, 6× CH),
0.85 (6H, s, 2× 18-CH3). 13C NMR (CDCl3, CD3OD, ı ppm): 154.1
(C-3), 137.9 (C-5), 131.8 (C-10), 126.1 (C-1), 115.1 (C-4), 112.6
(C-2), 82.9 (C-17), 72.0, 70.3, 69.9, 49.5, 46.7, 43.7, 39.6, 33.8,
33.2, 31.5, 29.6, 27.4, 26.3, 23.8, 23.3, 14.4 (C-18). MS (m/e): 712
(M+–H2O), 694 (M+–2 H2O). Exact mass: calculated for C46H64O6
(M+–H2O) = 712.4703; found = 712.4710.
2.1.2.7. Spectral data for dimer 6c (R = Bn). Forty-three percent
yield. IR (NaCl, ꢀmax, cm−1): 3426 (O–H), 1607 (C C), 1234 and
1025 (C–O). 1H NMR (C0DCl3, ı ppm): 7.42 (4H, d, J = 7.2 Hz, 2×
a-CH), 7.38 (4H, t, J = 7.6 Hz, 2× b-CH), 7.32 (2H, t, J = 7.2 Hz, 2×
c-CH), 7.20 (2H, d, J = 8.6 Hz, 2× 1-CH), 6.77 (2H, dd, J = 8.6 Hz
and 2.5 Hz, 2× 2-CH), 6.72 (2H, s, 2× 4-CH), 5.03 (4H, s, 2×
CH2Ph), 3.75–3.40 (20H, s, #m, 10× CH2O), 2,84 (4H, m, 2×
6-CH2), 2.48 (2H, sl, 2× OH), 2.35–1.20 (34H, #m, 14× CH2,
6× CH), 0.91 (6H, s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm):
156.7 (C-3), 138.0 (CCH2O), 137.3 (C-5), 133.0 (C-10), 128.5 (C-
b), 127.8 (C-c), 127.4 (C-a), 126.2 (C-1), 114.8 (C-4), 112.2 (C-2),
83.0 (C-17), 72.0, 70.6, 70.5, 70.0, 69.9 (CH2Ph), 49.5, 46.7, 43.8,
39.6, 34.4, 33.5, 31.6, 29.8, 27.5, 26.3, 24.0, 23.4, 14.4 (C-18).
MS (m/e): 980 (M+–H2O), 962 (M+–2 H2O), 889 (M+–H2O,–C7H7).
2.1.2.12. Spectral data for dimer 6b (R = H). IR (NaCl, ꢀmax
,
cm−1): 3346 (O–H), 1608 (C C), 1240 and 1092 (C–O). 1H NMR
(acetone-d6, CD3OD, ı ppm): 7.07 (2H, d, J = 8.4 Hz, 2× 1-CH),
6.56 (2H, dd, J = 8.6 Hz and J = 2.5 Hz, 2× 2-CH), 6.50 (2H, d,
J = 1.5 Hz, 2× 4-CH), 3.65–3.40 (16H, s and #m, 8× CH2O), 3.28
(4H, sl, 3-OH and 17-OH), 2.78 (4H, m, 2× 6-CH2), 2.35–1.20
(34H, #m, 14× CH2, 6× CH), 0.91 (6H, s, 2× 18-CH3). 13C NMR
(acetone-d6, CD3OD, ı ppm): 155.9 (C-3), 138.5 (C-5), 132.1 (C-
10), 127.0 (C-1), 115.9 (C-4), 113.5 (C-2), 83.1 (C-17), 72.7, 71.4,
71.3, 70.9, 50.5, 47.7, 44.8, 40.9, 34.7, 34.2, 32.6, 29.6 (hidden
by acetone), 28.5, 27.4, 25.1, 24.2, 15.1 (C-18). MS (m/e): 756
(M+–H2O), 738 (M+–2 H2O). Exact mass: calculated for C48H68O7
(M+–H2O) = 756.4965; found = 756.4976.
Exact mass: calculated for
found = 980.6187.
C64H84O8 (M–H2O) = 980.6166;
2.1.2.8. Spectral data for dimer 6d (R = Bn). Forty percent yield.
IR (NaCl, ꢀmax, cm−1): 3448 (O–H), 1608 (C C), 1235 and 1104
(C–O). 1H NMR (CDCl3, ı ppm): 7.42 (4H, d, J = 7.5 Hz, 2× a-
CH), 7.37 (4H, t, J = 7.4 Hz, 2× b-CH), 7.31 (2H, t, J = 7.2 Hz, 2×
c-CH), 7.20 (2H, d, J = 8.6 Hz, 2× 1-CH), 6.77 (2H, dd, J = 8.7 Hz
and J = 2.4 Hz, 2× 2-CH), 6.71 (2H, d, J = 2.3 Hz, 2× 4-CH), 5.03
(4H, s, 2× CH2Ph), 3.70–3.45 (24H, 2s and #m, 12× CH2O), 2.83
(4H, m, 2× 6-CH2), 2.42 (2H, sl, 2× OH), 2.35–1.20 (34H, #m, 14×
CH2, 6× CH), 0.91 (6H, s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm):
156.7 (C-3), 138.0 (CCH2O), 137.3 (C-5), 133.0 (C-10), 128.5 (C-b),
127.8 (C-c), 127.4 (C-a), 126.2 (C-1), 114.8 (C-4), 112.2 (C-2), 82.9
(C-17), 72.0, 70.5, 70.0, 69.9 (CH2Ph), 49.5, 46.7, 43.8, 39.6, 34.4,
33.5, 31.6, 29.8, 27.5, 26.3, 24.0, 23.4, 14.4 (C-18). MS: above the
detection limit of the mass spectrometer used.
2.1.2.13. Spectral data for dimer 6c (R = H). IR (NaCl, ꢀmax
,
cm−1): 3385 (O–H), 1610 (C C), 1287 and 1036 (C–O). 1H NMR
(CDCl3, ı ppm): 7.05 (2H, d, J = 8.5 Hz, 2× 1-CH), 6.59 (2H, d,
J = 8.2 Hz, 2× 2-CH), 6,51 (2H, d, J = 1,4 Hz, 2× 4-CH), 3.65–3.42
(20H, s and #m, 10× CH2O), 3.06 (4H, br s, 3-OH and 17-OH), 2.76
(4H, m, 2× 6-CH2), 2.30–1.15 (34H, #m, 14× CH2, 6× CH), 0.84
(6H, s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm): 155.1 (C-3), 138.9 (C-
5), 132.7 (C-10), 127.1 (C-1), 116.2 (C-4), 113.6 (C-2), 84.0 (C-17),
73.0, 71.3, 70.8, 50.4, 47.7, 44.6, 40.6, 34.8, 34.2, 32.5, 30.6, 28.4,
27.2, 24.8, 24.3, 15.4 (C-18). MS (m/e): 800 (M+–H2O), 782 (M+–2
2.1.2.9. Spectral data for dimer 6e (R = Bn). Forty percent yield.
IR (NaCl, ꢀmax, cm−1): 3458 (O–H), 1603 (C C), 1252 and 1025
(C–O). 1H NMR-(CDCl3, ı ppm): 7.42 (4H, d, J = 7.3 Hz, 2× a-
CH), 7.38 (4H, t, J = 7.4 Hz, 2× b-CH), 7.31 (2H, t, J = 7.3 Hz, 2×
c-CH), 7.20 (2H, d, J = 8.7 Hz, 2× 1-CH), 6.77 (2H, dd, J = 8.7 Hz and
J = 2.4 Hz, 2× 2-CH), 6.72 (2H, d, J = 2.3 Hz, 2× 4-CH), 5.03 (4H, s,
2× CH2Ph), 3.70–3.45 (28H, 2s, m and t, 14× CH2O), 2.84 (4H, m,
2× 6-CH2), 2.40–1.20 (36H, #m, 14× CH2, 6× CH, 2× OH), 0.91
(6H, s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm): 157.7 (C-3), 139.0
(CCH2O), 138.3 (C-5), 134.0 (C-10), 129.5 (C-b), 128.7 (C-c), 128.4
(C-a), 127.2 (C-1), 115.7 (C-4), 113.2 (C-2), 83.9 (C-17), 73.0, 71.5,
71.0, 70.9 (CH2Ph), 50.5, 47.7, 44.8, 40.6, 35.4, 34.5, 32.6, 30.8,
28.5, 27.3, 25.0, 24.4, 14.4 (C-18). MS: above the detection limit
of the mass spectrometer used.
H2O). Exact mass: calculated for C50
found = 800.5231.
H
72O8 (M+–H2O) = 800.5227;
2.1.2.14. Spectral data for dimer 6d (R = H). IR (NaCl, ꢀmax
,
cm−1): 3383 (O–H), 1611 (C C), 1248 and 1100 (C–O). 1H NMR
(CDCl3, ı ppm): 7.08 (2H, d, J = 8.6 Hz, 2× 1-CH), 6.61 (2H, dd,
J = 8.6 Hz and J = 2.5 Hz, 2× 2-CH), 6.54 (2H, d, J = 1.4 Hz, 2× 4-
CH), 3.68–3.48 (24H, 2m, 12× CH2O), 2.76 (4H, m, 2× 6-CH2),
2.37–1.10 (38H, #m, 14× CH2, 6× CH, 3-OH, 17-OH), 0.87 (6H,
s, 2× 18-CH3). 13C NMR (CDCl3, ı ppm): 154.0 (C-3), 137.9 (C-
5), 132.0 (C-10), 126.2 (C-1), 115.3 (C-4), 112.8 (C-2), 83.2 (C-17),
72.1, 70,5, 70.0, 49.4, 46.7, 43.6, 39.6, 34.2, 33.5, 31.5, 29.7, 27.4,
26.3, 23.9, 23.3, 14,4 (C-18). MS (m/e): 844 (M+–H2O), 826 (M+–2
H2O). Exact mass: calculated for C52H76O9 (M+–H2O) = 844.5489;
found = 844.5515.
2.1.2.10. General procedure for the synthesis of dimers 6 (a–e)
(R = H). Palladium on carbon (10%, 10 mg) was added to a solu-