L. G. Luyt et al. / Bioorg. Med. Chem. 11 (2003) 4977–4989
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was stirred for 30min. A portion of 3- tbutyldimethylsi-
lanyloxy-estrone (377 mg, 0.98 mmol) dissolved in 5 mL
THF was slowly added, and the reaction was main-
tained at ꢀ78 ꢁC for 8 h, and then warmed to room
temperature overnight. The reaction was quenched with
satd NH4Cl, the organics were extracted with CHCl3
(3ꢃ), the combined organics were washed with brine,
dried over Na2SO4, evaporated and dried under vacuum.
Purification was carried out by flash chromatography
(silica, gradient 10% ethyl acetate/90% hexanes to 20%
ethyl acetate/80% hexanes) yielding 329 mg (53%) of a
(CDCl3): d 0.83 (s, 3H), 1.19 (t, 3H, J=7.5 Hz), 1.20(t,
3H, J=7.5 Hz), 1.30–1.40 (4H), 1.65 (m, 1H), 1.72 (m,
1H), 1.85 (m, 1H), 1.90–1.97 (m, 2H), 2.12 (m, 1H), 2.22
(m, 2H), 2.32 (m, 1H), 2.64–2.78 (6H), 2.93/3.01 (AB,
2H, J=18.7 Hz), 6.45 (d, 1H, J=2.6 Hz), 6.52 (dd, 1H,
J=2.6, 8.4 Hz), 7.06 (d, 1H, J=8.4 Hz). 13C NMR
(CDCl3): d 13.41, 14.12, 23.72, 25.29, 25.36, 27.84,
28.67, 30.17, 30.77, 33.88, 39.83, 41.23, 44.88, 48.63,
50.16, 67.62, 80.65, 82.62, 87.61, 113.73, 116.04, 127.26,
132.73, 138.84, 155.87, 176.46. MS (EI): m/z 488 (M+,
1%), 487 (M-H, 1%), 470(M ꢀH2O, 4%); HRMS calcd
C27H35O4S2, 487.1977, found 487.1975.
1
clear, pale yellow oil. H NMR (CDCl3): d 0.19 (s, 6H),
0.85 (s, 3H), 0.98 (s, 9H), 1.23 (t, 6H, J=7.5 Hz), 1.31 (t,
3H, J=7.3 Hz), 1.32–1.50(4H), 1.63–2.01 (6H), 2.22–
2.33 (3H), 2.68 (m, 4H), 2.79 (m, 2H), 2.96 (d, 2H, J=3.0
Hz), 4.24 (q, 2H, J=7.1 Hz), 6.55 (d, 1H, J=2.6 Hz),
6.61 (dd, 1H, J=2.6, 8.4 Hz), 7.12 (d, 1H, J=8.6 Hz).
13C NMR (CDCl3): d ꢀ4.45, 12.65, 13.66, 13.69, 14.08,
18.11, 22.69, 24.20, 24.24, 25.66, 26.38, 27.26, 28.51,
29.60, 32.47, 38.88, 39.35, 43.41, 47.33, 49.00, 62.29,
17ꢀ-(60,60-Bis(ethanethio)-60-carboxy-hexyn-10-yl)-estra-
1,3,5(10)-triene-3,17ꢁ-diol (20b). A flask with attached
condenser was charged with 19b (210mg, 0.32 mmol),
12 mL MeOH, and 12 mL 3 M NaOH aqueous solu-
tion. The mixture was heated at reflux overnight, cooled
to room temperature, and the methanol was evaporated
in vacuo. The aqueous solution was made slightly acidic
with the addition of 3 M HCl. The organics were
extracted with CHCl3 (4ꢃ), the combined organics were
washed with brine, dried over Na2SO4, evaporated and
dried under vacuum. Purification was carried out by
flash chromatography (silica, gradient: 0–20% MeOH/
63.66, 79.95, 80.87, 87.06, 117.09, 119.88, 126.12,
+
133.17, 137.85, 153.24, 169.59 . MS (EI): m/z 630(M
,
73%); HRMS calcd C35H54O4SiS2, 630.3233, found,
630.3232.
17ꢀ-(60,60-Bis(ethanethio)-60-ethoxycarbonyl-hexyn-10-yl)-
3-tbutyldimethylsilanyloxy-estra-1,3,5(10)-triene-17ꢁ-ol
(19b). A flame-dried flask was charged with alkyne 16b
(290mg, 1.06 mmol) and 10mL THF, and then was
cooled to ꢀ78 ꢁC. A 1.1 mL portion of 1.0M n-butyl
lithium was slowly added via syringe and the reaction
was stirred for 30min. A portion of 3- tbutyldimethyl-
silanyloxy-estrone (333 mg, 0.87 mmol) dissolved in 5
mL THF was slowly added, and the reaction was
maintained at ꢀ78 ꢁC for 6 h, and then warmed to room
temperature overnight. Workup and purification were
carried out as described for 19a, yielding 264 mg (46%)
CHCl3) to give a clear, colorless oil (129 mg, 78%). H
1
NMR (CD3OD): d 0.84 (s, 3H), 1.14 (dt, 6H, J=2.8, 7.5
Hz), 1.36–1.41 (4H), 1.67–1.79 (5H), 1.85 (m, 1H), 1.95
(m, 2H), 2.06 (m, 2H), 2.17–2.26 (2H), 2.30 (t, 2H,
J=6.5), 2.34 (m, 1H), 2.59 (m, 4H), 2.75 (m, 2H), 6.46
(d, 1H, J=2.6), 6.53 (dd, 1H, J=2.6, 8.4), 7.07 (d, 1H,
J=8.4). 13C NMR (CD3OD): d 13.47, 13.93, 19.32,
23.73, 24.62, 24.70, 25.74, 27.75, 28.56, 30.78, 34.24,
37.17, 39.96, 41.14, 45.05, 48.43, 50.84, 67.97, 80.56,
85.73, 85.86, 113.68, 116.00, 127.31, 132.57, 138.82,
155.85, 175.55.
of a clear, colorless oil. H NMR (CDCl3): d 0.18 (s,
17ꢀ-(40,40-Bis(ethanethio)-40-carboxy-butyn-10-yl)-estra-
1,3,5(10)-triene-3,17ꢁ-diol rhenium(I) tricarbonyl (21a).
Compound 20a (27 mg, 0.054 mmol) was dissolved in 1
mL MeOH, 1 mL water, and 100 mL of satd NaHCO3.
The solution was heated to 70 ꢁC and 337 mL of a
0.178 M Re(CO)+3 aqueous solution was added. After
90min the solution was cooled and evaporated to dry-
ness under vacuum. The crude material was purified by
flash chromatography (silica, gradient: 0–20% MeOH/
CHCl3) to give 12 mg (29%) of 21a. 1H NMR
(CD3OD): d 0.88 (s, 3H), 1.12–1.49 (10H), 1.76–2.07
(6H), 2.16–2.38 (3H), 2.64–2.81 (8H), 6.48 (d, 1H,
J=2.4 Hz), 6.54 (dd, 1H, J=2.4, 8.1 Hz), 7.09 (d, 1H,
J=8.1 Hz). MS (FAB): m/z 759 (M[187Re]++H, 2.9%),
757 (M[185Re]++H, 2.2%), 741 (M[187Re]+ꢀOH,
2.7%), 739 (M[185Re]+ꢀOH, 1.7%). HRMS calcd
C30H35O7S2Re, 759.1460, found 759.1457.
1
6H), 0.87 (s, 3H), 0.97 (s, 9H), 1.20 (t, 6H, J=7.5 Hz),
1.29 (t, 3H, J=7.1 Hz), 1.32 to 1.51 (4H), 1.64–1.90
(7H), 2.01 (m, 1H), 2.08 (m, 2H), 2.20–2.36 (5H), 2.63
(m, 4H), 2.80(m, 2H), 4.22 (q, 2H, J=7.1 Hz), 6.55 (d,
1H, J=2.6 Hz), 6.61 (dd, 1H, J=2.6, 8.4 Hz), 7.12 (d,
1H, J=8.4 Hz). 13C NMR (CDCl3): d ꢀ4.46, 12.78,
13.49, 14.08, 14.09, 18.11, 18.63, 22.76, 23.63, 23.70,
24.49, 25.65, 26.33, 27.18, 29.62, 32.93, 35.54, 39.05,
39.33, 43.59, 47.14, 49.53, 62.08, 64.63, 80.00, 84.53,
85.33, 117.11, 119.88, 126.14, 133.01, 137.82, 153.22,
170.42 . MS (EI): m/z (M+, 1%); HRMS calcd
C37H58O4SiS2, 658.3546, found, 658.3548.
17ꢀ-(40,40-Bis(ethanethio)-40-carboxy-butyn-10-yl)-estra-
1,3.5(10)-triene-3, 17ꢁ-diol (20a). A flask with attached
condenser was charged with 19a (253 mg, 0.40 mmol),
12 mL MeOH, and 12 mL 3 M NaOH aqueous solu-
tion. The mixture was heated at reflux for 5 h, cooled to
room temperature, and made slightly acidic with the
addition of 1 M HCl. The organics were extracted with
CHCl3 (3ꢃ), the combined organics were washed with
brine, dried over Na2SO4, evaporated and dried under
vacuum. Purification was carried out by flash chroma-
tography (silica, gradient: 0–30% MeOH/CHCl3) to
give a clear, colorless oil (128 mg, 65%). 1H NMR
17ꢀ-(60,60-Bis(ethanethio)-60-carboxy-hexyn-10-yl)-estra-
1,3,5(10)-triene-3,17ꢁ-diol rhenium(I) tricarbonyl (21b).
Compound 20b (26 mg, 0.051 mmol) was dissolved in 2
mL methanol, 2 mL water, and 52 mL of 1 M NaOH.
The solution was heated to 70 ꢁC and 500 mL of a
0.122 M Re(CO)+3 aqueous solution was added. After
15 min the solution was cooled and evaporated to dry-
ness under vacuum. The crude material was purified by