GModel
SBMB-3949; No. of Pages13
ARTICLE IN PRESS
S. Parihar et al. / Journal of Steroid Biochemistry & Molecular Biology xxx (2013) xxx–xxx
3
5H, Ar H); 13C NMR (CDCl ): ı 12.30, 21.02, 21.30, 23.61, 26.22,
2.2.4. Z-2-[2-(3,4-Dimethoxyphenyl)vinyl)-estra
3
1
,3,5(10)-trien-3,17-diacetate (16)
27.35, 27.98, 29.52, 37.32, 38.72, 43.28, 44.24, 50.40, 83.01, 101.16,
108.39, 109.37, 122.45, 123.38, 124.10, 127.61, 127.75, 131.32,
131.68, 137.73, 138.12, 146.83, 147.15, 147.77, 169.47, 171.21; ESI
1
H NMR (CDCl ): ı 0.74 (s, 3H, 18-CH ), 0.87–1.95 (m, 13H, rest
3
3
of the 5xCH2 and 3xCH of steroidal ring), 2.09 (s, 3H, 17-OCOCH ),
3
+
+
+
2
3
1
6
2
4
1
1
.28 (s, 3H, 3-OCOCH ), 2.82 (bs, 2H, 6-CH ), 3.58 (s, 3H, OCH ),
mass (MeOH): 503 [M+H] , 525 [M+Na] , 541 [M+K] , Negative
3
2
3
−
−1
.89 (s, 3H, OCH ), 4.60–4.66 (t, 1H, 17-CH, J = 8.3 Hz), 6.32–6.36 (d,
mode: 501 [M−H] ; IR (KBr, cm ): 2925, 1753, 1723, 1508, 1490,
3
H, CH-vinylic, J = 12 Hz), 6.51–6.55 (d, 1H, CH-vinylic, J = 12 Hz),
.69–7.15 (m, 5H, 1-CH, 4-CH & Ar H); C NMR (CDCl ): ı 12.28,
0.97, 21.25, 23.60, 26.24, 27.40, 27.96, 29.49, 37.22, 38.83, 43.24,
4.24, 50.37, 55.93, 56.34, 82.96, 111.79, 112.97, 122.43, 123.99,
27.88, 128.28, 130.47, 131.66, 137.50, 138.16, 146.98, 149.07,
1243.
13
3
2.2.9. E-2-[2-(3,4-Methylenedioxyphenyl)vinyl)-estra
1,3,5(10)-trien-3,17-diacetate (25)
1
H NMR (CDCl ): ı 0.84 (s, 3H, 18-CH ), 1.23–2.29 (m, 13H, rest
3
3
+
+
69.47, 171.15; ESI mass (MeOH): 541 [M+Na] , 557 [M+K] , Neg-
of the 5xCH2 and 3xCH of steroidal ring), 2.05 (s, 3H, 17-OAc), 2.37
−
−1
ative mode: 517 [M−H] ; IR (KBr, cm ): 2929, 1752, 1736, 1655,
(s, 3H, 3-OAc), 2.85 (t, 2H, 6-CH , J = 3.6 Hz), 4.67–4.73 (t, 1H, 17-
2
1
510, 1246.
CH, J = 8.4 Hz), 5.97 (s, 2H,
J = Hz), 6.60 (d, 1H, CH, vinylic, J = Hz), 6.80–7.53 (m, 5H, Ar H);
O CH2 O ), 6.3 (d, 1H, CH, vinylic,
13
C
2.2.5. Z-2-[2-(3,5-Dimethoxyphenyl)vinyl)-estra
NMR (CDCl ):ı 12.37, 21.14, 21.28, 23.64, 26.54, 27.43, 28.01, 29.58,
3
1
,3,5(10)-trien-3,17-diacetate (18)
37.39, 38.76, 43.33, 44.45, 50.51, 83.02, 101.42, 106.08, 108.73,
121.57, 121.76, 122.82, 123.84, 127.55, 130.06, 132.64, 137.79,
138.61, 146.57, 147.82, 148.60, 169.54, 171.20; ESI mass (MeOH):
525 [M+Na] , 541 [M+K] ; IR (KBr, cm ): 2928, 1735, 1720, 1507,
1498, 1249.
1
H NMR (CDCl ): ı 0.78 (s, 3H, 18-CH ), 0.84–1.91 (m, 13H, rest
3
3
of the 5xCH2 and 3xCH of steroidal ring), 2.05 (s, 3H, 17-OCOCH ),
2
4
3
+
+
−1
.19 (s, 3H, 3-OCOCH ), 2.83 (bs, 2H, 6-CH ), 3.63 (s, 6H, 2xOCH ),
3
2
3
.61–4.67 (t, 1H, 17-CH, J = 8.4 Hz), 6.41–6.45 (d, 1H, CH-vinylic,
J = 12 Hz), 6.53–6.57 (d, 1H, CH-vinylic, J = 12 Hz), 6.28–7.17 (m, 5H,
1
3
1
2
5
1
1
-CH, 4-CH & Ar H); C NMR (CDCl ): ı 12.25, 21.02, 21.30, 23.61,
2.2.10. E-2-[2-(4-Fluorophenyl)vinyl)-estra
3
6.15, 27.38, 27.97, 29.47, 37.23, 38.80, 43.24, 44.19, 50.34, 55.49,
5.49, 82.99, 100.48, 107.40, 107.40, 122.37, 125.64, 127.65, 127.93,
31.87, 137.71, 138.03, 139.30, 146.89, 161.01, 161.01, 169.47,
1,3,5(10)-trien-3-hydroxy,17-acetate (28)
1
H NMR (CDCl ): ı 0.85 (s, 3H, 18-CH ), 1.24–2.39 (m, 13H, rest
3
3
of the 5xCH2 and 3xCH of steroidal ring), 2.07 (s, 3H, 17-OAc), 2.82
+
+
+
71.20; ESI mass (MeOH): 519 [M+H] , 541 [M+Na] , 557 [M+K] ,
(bs, 2H, 6-CH ), 4.68–4.73 (t, 1H, 17-CH, J = 8.4 Hz), 6.53 (s, 1H, 1-
2
−
−1
Negative mode: 517 [M−H] ; IR (KBr, cm ): 2931, 1761, 1737,
CH), 7.02–7.07 (d, 1H, CH, vinylic, J = 16.2 Hz), 7.04 (s, 1H, 4-CH),
7.21–7.19 (d, 1H, CH, vinylic, J = 15.9 Hz), 7.44–7.51 (m, 4H, Ar H);
1
591, 1510, 1246, 1207, 1157.
+
ESI mass (MeOH): 459 [M+Na] .
2.2.6. E-2-[2-(3,5-Dimethoxyphenyl)vinyl)-estra
1
,3,5(10)-trien-3,17-diacetate (19)
2.2.11. Z-2-[2-(4-Methylphenyl)vinyl)-estra
1
H NMR (CDCl ): ı 0.77 (s, 3H, 18-CH ), 1.21–2.34 (m, 13H, rest
1,3,5(10)-trien-3,17-diol (29)
3
3
1
of the 5xCH2 and 3xCH of steroidal ring), 2.12 (s, 3H, 17-OCOCH ),
2
H NMR (CDCl ): ı 0.78 (s, 3H, 18-CH ), 1.08–2.21 (m, 13H,
3
3
3
ꢀ
.34 (s, 3H, 3-OCOCH ), 2.81 (bs, 2H, 6-CH ), 3.82 (s, 6H, 2xOCH ),
rest of the 5xCH2 and 3xCH of steroidal ring), 2.26 (s, 3H, 4 -CH ),
3
2
3
3
4
.60–4.66 (t, 1H, 17-CH, J = 8.4 Hz), 6.86–6.91 (d, 1H, CH-vinylic,
2.70 (bs, 2H, 6-CH ), 3.64–3.69 (t, 1H, 17-CH, J = 8.3 Hz), 6.93–7.31
2
13
J = 16.2 Hz), 6.95–7.00 (d, 1H, CH-vinylic, J = 16.5 Hz), 6.32–7.5 (m,
(m, 8H, Ar H, 2xCH vinylic); C NMR (CDCl ):ı 11.45, 21.49,
3
13
5
2
5
1
1
H, 1-CH, 4-CH & Ar H); C NMR (CDCl ): ı 12.41, 21.20, 21.37,
23.55, 26.83, 27.62, 29.73, 30.03, 31.01, 37.19, 39.36, 43.70, 44.38,
56.64, 82.37, 116.36, 122.79, 123.21, 124.41, 126.73, 126.73, 129.47,
129.67, 129.67, 133.35, 135.65, 137.49, 137.91, 151.54; ESI mass
3
3.66, 26.54, 27.41, 28.06, 29.63, 37.35, 38.70, 43.31, 44.41, 50.44,
5.72, 55.72, 83.03, 100.47, 105.32, 105.32, 122.91, 123.70, 124.12,
27.28, 130.40, 138.21, 138.66, 140.02, 146.68, 161.51, 161.51,
+
−1
(MeOH): 427 [M+K] ; IR (KBr, cm ): 3398, 2926, 1510, 1422, 1281,
1051.
+
+
69.64, 171.28; ESI mass (MeOH): 519 [M+H] , 541 [M+Na] , 557
+
−
−1
[
1
M+K] , Negative mode: 517 [M−H] ; IR (KBr, cm ): 2937, 1762,
722, 1593, 1459, 1250, 1205, 1156.
2.2.12. E-2-[2-(4-Methylphenyl)vinyl)-estra
1
,3,5(10)-trien-3-hydroxy,17-acetate (30)
1
2.2.7. Z-2-[2-(3,4,5-Trimethoxyphenyl)vinyl)-estra
H NMR (CDCl ): ı 0.84 (s, 3H, 18-CH ), 1.25–2.35 (m, 13H,
3
3
1
,3,5(10)-trien-3,17-diacetate (22)
rest of the 5xCH2 and 3xCH of steroidal ring), 2.07 (s, 3H, 17-
1
ꢀ
H NMR (CDCl ): ı 0.77 (s, 3H, 18-CH ), 1.17–2.23 (m, 13H,
OAc), 2.35 (s, 3H, 4 -CH ), 2.81 (bs, 2H, 6-CH ), 4.67–4.72 (t,
3
3
3
2
rest of the 5xCH2 and 3xCH of steroidal ring), 2.82 (bs, 2H, 6-
CH ), 3.64 (s, 6H, 2xOCH ), 3.82 (s, 3H, OCH ), 4.60–4.65 (t, 1H,
1H, 17-CH, J = 8.4 Hz), 6.54 (s, 1H, 1-CH), 7.01–7.06 (d, 1H, CH,
ꢀ
ꢀ
2
3
3
vinylic, J = 16.2 Hz), 7.14–7.17 (d, 2H, 3 & 5 -CH of aromatic ring,
J = 8.1 Hz), 7.24–7.29 (d, 1H, CH, vinylic, J = 16.2 Hz), 7.40 (s, 1H, 4-
1
2
7-CH, J = 8.3 Hz), 6.39–6.43 (d, 1H, CH-vinylic, J = 13 Hz), 6.44 (s,
H, Ar H), 6.51–6.55(d, 1H, CH-vinylic, J = 12 Hz), 6.78 (s, 1H, 1-
ꢀ
ꢀ
13
CH), 7.40–7.43 (d, 2H, 2 & 6 -CH of aromatic ring); C NMR (CDCl ):
3
13
CH), 7.14 (s, 1H, 4-CH); C NMR (CDCl ): ı 12.25, 20.96, 21.23,
ı 12.43, 21.40, 21.48, 23.66, 26.72, 27.60, 28.01, 29.69, 30.02, 37.38,
39.10, 43.37, 44.23, 50.39, 83.22, 116.37, 122.82, 123.21, 124.49,
126.73, 126.73, 129.67, 129.67, 133.27, 135.64, 137.50, 137.83,
3
2
6
1
3.59, 26.23, 27.39, 27.95, 29.47, 37.18, 38.88, 43.21, 44.26, 50.35,
1.07, 82.91, 107.37, 107.37, 122.44, 125.05, 127.92, 128.07, 131.86,
32.64, 137.60, 137.60, 138.09, 147.02, 153.28, 169.41, 171.09; EI
+
−1
151.55, 171.59; ESI mass (MeOH): 431 [M+H] ; IR (KBr, cm ):
3448, 2930, 1702, 1510, 1422, 1276, 1249.
+
+
−1
mass (MeOH): 548 [M ], 549 [M+1] ; IR (KBr, cm ): 3449, 2851,
2
370, 1736, 1720, 1597, 1509, 1244, 1127.
2.2.13. Z-2-[2-(2-Methoxyphenyl)vinyl)-estra
2
.2.8. Z-2-[2-(3,4-Methylenedioxyphenyl)vinyl)-estra
1,3,5(10)-trien-3,17-diacetate (31)
1
1,3,5(10)-trien-3,17-diacetate (24)
H NMR (CDCl ): ı 0.75 (s, 3H, 18-CH ), 0.84–2.25 (m, 13H, rest
3
3
1
H NMR (CDCl ): ı 0.79 (s, 3H, 18-CH ), 1.21–1.88 (m, 13H, rest
of the 5xCH2 and 3xCH of steroidal ring), 2.04 (s, 3H, 17-OAc), 2.21
(s, 3H, 3-OAc), 2.79 (bs, 2H, 6-CH ), 3.83 (s, 3H, OCH ), 4.60–4.66
(t, 1H, 17-CH, J = 8.4 Hz), 6.44–6.48 (d, 1H, CH, vinylic), 6.71 (s, 1H,
3
3
of the 5xCH2 and 3xCH of steroidal ring), 2.05 (s, 3H, 17-OAc), 2.19
s, 3H, 3-OAc), 2.84 (bs, 2H, 6-CH ), 4.61–4.67 (t, 1H, 17-CH), 5.87 &
2
3
(
2
5
.91 (two distinct singlets, 2H, 6-CH ), 6.29–6.32 (d, 1H, CH, vinylic,
2
13
J = 12 Hz), 6.48–6.52 (d, 1H, CH, vinylic, J = 12.3 Hz), 6.66–7.17 (m,
C NMR (CDCl ): ı 11.67, 20.52, 20.89, 22.92, 25.28, 26.65, 27.20,
3
Please cite this article in press as: S. Parihar, et al., Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer