Synthesis of Steroid-Biaryl Ether Hybrid Macrocycles
1151.5894. Anal. found: C, 62.5; H, 7.2; N, 7.8. Calcd.
NaO15
N
6
51.4, 45.1, 43.6, 43.7, 42.1, 37.6, 37.4, 37.2, 35.1, 32.8, 31.9, 30.3,
C, 62.0; H, 6.9; N, 8.0.
29.7, 28.4, 26.7, 22.5, 22.2, 21.9, 21.4, 19.3, 12.7; HRMS (ESI-
Macrocycle 7: mp (from MeOH) 289-292 °C; IR (KBr, cm-1
)
+
FT-ICR) m/z 1015.5033 [M + H] , calcd for C53
H
71
N
6
O
14
3
1
2
1
1
0
1
1
4
4
2
1
445, 3321, 3092, 3008, 2951, 2865, 1728, 1698, 1656, 1502, 1219,
1015.5023. Anal. found: C, 62.7; H, 6.95; N, 8.2. Calcd: C, 62.4;
H, 6.7; N, 8.3.
1
056; H NMR (CDCl ) δ ) 8.93 (m, 2H), 7.43 (m, 2H), 7.39 (d,
3
-
1
H), 7.23-7.21 (m, 10H), 6.89 (m, 2H), 6.83 (m, 2H), 4.50 (m,
H), 4.39 (m, 2H), 4.19-4.11 (m, 4H), 3.87 (m, 1H), 3.81 (m,
H), 3.68, 3.66 (s, 6H), 0.96 (s, 3H), 0.82 (d, 3H, J ) 5.9 Hz),
Macrocycle 16: mp (from CH
3
CN) 228-230 °C; IR (KBr, cm )
3288, 3076, 2928, 2872, 1697, 1649, 1610, 1500, 1216, 1179, 1079,
1
980, 912; H NMR (CDCl
3
) δ ) 9.61 (m, 1H), 9.18 (m, 1H), 7.53
.70 (s, 3H); 13C NMR (CDCl
(m, 2H), 7.19 (m, 2H), 6.90 (m, 2H), 6.79 (m, 2H), 4.84 (m, 2H),
4.74 (m, 2H), 4.37 (m, 1H), 4.17-3.92 (m, 4H), 3.80-3.77 (m,
2H), 1.34 (d, 6H, J ) 6.0 Hz), 1.26 (d, 6H, J ) 6.3 Hz), 1.06 (d,
3H, J ) 6.4 Hz), 0.90 (s, 3H), 0.86 (s, 3H), 0.80 (d, 3H, J ) 6.0
3
) δ ) 175.2, 175.0, 172.7, 171.8,
70.7, 169.0, 168.8, 153.5, 135.4, 133.4, 129.4, 128.8, 127.1, 121.4,
21.1, 120.0, 119.6, 119.5, 75.9, 68.6, 68.2, 53.2, 52.8, 52.6, 49.6,
9.3, 48.8, 46.6, 46.2, 46.1, 45.9, 45.5, 44.2, 44.0, 43.3, 43.1, 41.2,
1.0, 39.6, 39.3, 35.1, 34.3, 34.1, 33.4, 30.8, 32.7, 30.6, 29.9, 29.8,
Hz); 13C NMR (CDCl
) δ ) 172.4, 171.0, 169.6, 167.8, 164.0,
3
8.3, 26.0, 23.7, 21.7, 17.2, 13.1; HRMS (ESI-FT-ICR) m/z
163.2, 155.3, 134.3, 132.7, 121.4, 120.4, 119.7, 119.2, 109.3, 79.9,
71.7, 71.5, 66.8, 56.0, 51.6, 48.9, 47.9, 46.8, 45.3, 42.0, 36.3, 34.2,
+
133.5438 [M + Na] , calcd for C64
H78NaO13N
4
1133.5435. Anal.
found: C, 69.55; H, 7.3; N, 5.4. Calcd: C, 69.2; H, 7.1; N, 5.0.
33.9, 31.4, 30.7, 30.2, 28.7, 20.9, 17.6, 17.1, 13.2, 10.6; HRMS
-
1
+
Macrocycle 8: mp (from MeOH) 202-203 °C; IR (KBr, cm
521, 3334, 3009, 2939, 2871, 1728, 1666, 1641, 1506, 1168; H
)
(ESI-FT-ICR) m/z 959.5259 [M + Na] , calcd for C53
H
72NaO N
9 6
1
3
959.5253. Anal. found: C, 63.9; H, 8.1; N, 5.6. Calcd: C, 64.3;
H, 8.5; N, 5.8.
NMR (CDCl ) δ ) 9.15 (m, 1H), 8.72 (m, 1H), 7.49 (d, 2H, J )
3
8
6
4
.4 Hz), 7.41 (d, 2H, J ) 8.4 Hz), 7.34 (m, 2H), 6.88 (m, 4H),
3
Macrocycle 18: mp (from CH OH) 217-220 °C; IR (KBr,
cm- ) 3516, 3342, 3292, 2947, 2868, 1725, 1690, 1666, 1500, 980,
1
.71 (m, 2H), 4.54 (m, 1H), 4.47 (m, 2H), 4.21-4.18 (m, 2H),
.17-4.15 (m, 2H), 4.07 (m, 1H), 3.97 (m, 1H), 3.71 (s, 6H), 1.06
1
912; H NMR (CDCl
3
) δ ) 8.97 (m, 1H), 9.35 (m, 1H), 7.50 (m,
(
d, 3H, J ) 6.4 Hz), 0.89 (s, 3H), 0.67 (s, 3H); 13C NMR (CDCl
3
)
2H), 7.31 (m, 2H), 6.94 (m, 2H), 6.82 (m, 2H), 4.65 (m, 2H), 4.58
(m, 2H), 4.39 (m, 1H), 4.22-4.17 (m, 4H), 4.16-4.10 (m, 2H),
3.77 (s, 6H), 1.50 (d, 3H, J ) 7.1 Hz), 1.48 (d, 3H, J ) 6.8 Hz),
1.05 (d, 3H, J ) 6.3 Hz), 0.92 (s, 3H), 0.89 (s, 3H), 0.78 (d, 3H,
δ ) 175.2, 174.8, 173.1, 172.9, 168.6, 168.2, 153.5, 133.5, 139.2,
1
5
4
3
35.7, 117.0, 116.9, 121.5, 121.3, 119.2, 118.9, 77.2, 71.0, 68.4,
5.2, 53.8, 52.7, 52.5, 52.0, 52.3, 52.0, 49.3, 47.0, 46.6, 46.0, 46.4,
5.8, 41.8, 41.4, 41.2, 39.4, 35.4, 35.0, 34.8, 34.4, 34.1, 32.8, 31.4,
J ) 6.2 Hz); 13C NMR (CDCl
) δ ) 175.4, 174.9, 172.0, 171.2,
3
0.3, 29.2, 28.2, 26.5, 23.1, 19.6, 17.3, 12.7; HRMS (ESI-FT-
169.8, 168.3, 165.1, 164.7, 155.2, 155.0, 134.8, 132.3, 121.2, 120.8,
119.6, 119.4, 109.3, 80.2, 71.2, 70.7, 66.8, 61.8, 55.8, 44.7, 42.2,
41.5, 40.8, 39.5, 34.1, 31.7, 31.2, 30.1, 28.7, 26.8, 26.2, 22.2, 21.9,
+
ICR) m/z 1113.5279 [M + Na] , calcd for C58
H74NaO13N
8
1
113.5277. Anal. found: C, 64.0; H, 7.0; N, 10.7. Calcd: C, 63.8;
H, 6.8; N, 10.3.
Macrocycle 10: mp (from CH
21.1, 17.2, 16.6, 14.5, 13.9; HRMS (ESI-FT-ICR) m/z 1047.5059
-
1
+
[M + Na] , calcd for C55
H72NaO13
N
6
1047.5055. Anal. found: C,
3
CN) 266-268 °C; IR (KBr, cm )
3
1
8
494, 3274, 3205, 2975, 2948, 2869, 1741, 1698, 1677, 1641, 1500,
215, 1169; H NMR (CDCl
.8 Hz), 7.38 (d, 2H, J ) 8.4 Hz), 6.85 (d, 2H, J ) 9.2 Hz), 6.81
64.2; H, 7.3; N, 8.0. Calcd: C, 64.4; H, 7.1; N, 8.2.
Macrocycle 20: mp (from CH CN) 245-246 °C; IR (KBr, cm )
3434, 3056, 3019, 2937, 2871, 1728, 1666, 1604, 1213, 1172; H
NMR (CDCl
1
-1
3
) δ ) 8.90 (m, 2H), 7.42 (d, 2H, J )
3
1
(
2
0
d, 2H, J ) 8.8 Hz), 4.76-4.63 (m, 4H), 4.33 (m, 2H), 4.20 (m,
3
) δ ) 9.45 (m, 1H), 9.36 (m, 1H), 7.41 (m, 2H),
H), 3.94 (m, 2H), 3.90 (m, 1H), 3.67 (s, 3H), 1.28-1.19 (m, 12H),
7.36 (m, 2H), 7.23 (m, 10H), 6.98 (m, 2H), 6.84 (m, 2H), 4.57 (m,
2H), 4.42 (m, 4H), 4.37 (m, 2H), 4.33 (m, 2H), 3.92 (m, 1H), 3.79
13
.98 (d, 3H, J ) 6.4 Hz), 0.93 (s, 3H), 0.91 (s, 3H); C NMR
) δ ) 174.8, 171.0, 168.1, 167.8, 166.0, 163.0, 162.8, 155.0,
1
3
(CDCl
3
(m, 1H), 0.97 (s, 3H), 0.92 (d, 3H, J ) 6.2 Hz), 0.84 (s, 3H);
C
1
5
3
1
54.2, 133.6, 133.4, 121.2, 120.5, 119.6, 119.3, 72.6, 71.1, 67.8,
2.0, 51.5, 50.0, 49.5, 49.0, 48.7, 47.5, 45.8, 42.0, 39.1, 37.0, 35.6,
4.2, 33.8, 31.6, 30.5, 29.2, 27.4, 26.9, 23.4, 22.0, 20.9, 20.7, 20.6,
NMR (CDCl ) δ ) 174.7, 171.0, 169.1, 167.8, 161.9, 160.2, 155.0,
154.9, 137.1, 134.6, 134.0, 128.2, 127.8, 127.4, 120.5, 120.2, 119.7,
118.9, 71.1, 70.9, 70.2, 68.2, 47.5, 47.3, 45.6, 43.5, 42.8, 41.7, 36.6,
3
+
9.8, 12.3; HRMS (ESI-FT-ICR) m/z: 949.5041 [M + Na] ,
35.8, 35.2, 34.3, 33.9, 32.9, 31.8, 30.4, 28.4, 19.1, 16.1, 12.3; HRMS
+
calcd for C51
H70NaN
6
O
10 949.5045. Anal. found: C, 66.5; H, 7.6;
(ESI-FT-ICR) m/z 960.4882 [M + Na] , calcd for C56
H
67NaO N
8 5
N, 9.0. Calcd. C, 66.1; H, 7.6; N, 9.1.
Macrocycle 12: mp (from CH OH) 236-237 °C; IR (KBr,
cm ) 3434, 3327, 3054, 3025, 2978, 2939, 2870, 1738, 1619, 1648,
960.4887. Anal. found: C, 71.5; H, 7.0; N, 7.9. Calcd: C, 71.7;
H, 7.2; N, 7.4.
3
-1
Macrocycle 22: mp (from acetone) 214-216 °C; IR (KBr,
1
-1
1
2
2
2
1
502, 1206, 1170; H NMR (CDCl
3
) δ ) 8.95 (m, 2H), 7.44 (d,
cm ) 3434, 3273, 3006, 2972, 2954, 2869, 1735, 1701, 1695, 1649,
1
H, J ) 8.6 Hz), 7.40 (d, 2H, J ) 8.5 Hz), 7.27 (m, 10H), 6.88 (d,
H, J ) 8.8 Hz), 6.84 (d, 2H, J ) 8.8 Hz), 4.66 (m, 2H), 4.61 (m,
H), 4.38 (m, 4H), 4.31-4.26 (m, 4H), 3.66 (s, 3H), 3.55 (m, 1H),
.12 (s, 3H), 0.92 (d, 3H, J ) 6.6 Hz), 0.89 (s, 3H); 13C NMR
1499, 1212; H NMR (CDCl
3
) δ ) 9.40 (m, 1H), 9.25 (m, 1H),
7.43 (m, 2H), 7.34 (m, 2H), 6.92 (m, 2H), 6.80 (m, 2H), 4.74-
4.70 (m, 2H), 4.54 (m, 2H), 4.40 (m, 2H), 4.00 (m, 2H), 3.86 (m,
1H), 3.70 (m, 1H), 1.27-1.25 (m, 12H), 0.95 (s, 3H), 0.88 (s, 3H),
(CDCl
3
) δ ) 175.9, 171.4, 169.9, 168.4, 167.8, 162.9, 162.7, 155.1,
0.87 (d, 3H, J ) 7.0 Hz); 13C NMR (CDCl
) δ ) 175.8, 170.9,
3
1
1
3
1
54.5, 137.4, 133.8, 133.5, 128.4, 127.8, 127.1, 121.1, 120.8, 119.8,
19.7, 72.5, 71.8, 70.2, 52.5, 51.7, 48.9, 48.8, 45.1, 43.8, 43.7, 42.7,
7.6, 37.8, 35.8, 32.1, 31.9, 30.5, 29.8, 28.7, 26.4, 22.1, 21.7, 19.5,
168.5, 166.0, 160.0, 155.0, 154.9, 134.6, 134.0, 120.4, 120.3, 119.4,
118.9, 71.6, 71.5, 69.2, 50.2, 47.5, 47.3, 45.6, 43.5, 42.8, 41.7, 36.6,
34.3, 33.9, 32.9, 31.8, 30.4, 28.4, 22.0, 21.5, 21.3, 20.9, 20.2, 19.3,
16.8, 12.9; HRMS (ESI-FT-ICR) m/z 864.4855 [M + Na] , calcd
8 5
for C48H67NaO N 864.4881. Anal. found: C, 68.1; H, 8.0; N, 8.1.
+
+
2.7; HRMS (ESI-FT-ICR) m/z 1045.5055 [M + Na] , calcd for
C
59
H70NaN
6
O10 1045.5052. Anal. found: C, 69.4; H, 6.7; N, 8.5.
Calcd: C, 69.25; H, 6.9; N, 8.2.
Calcd: C, 68.5; H, 8.0; N, 8.3.
Macrocycle 14: mp (from CH
3
OH) 266-268 °C; IR (KBr,
Macrocycle 23: Mixture of regiomers; IR (KBr, cm-1) 3434,
-1
1
cm ) 3512, 3336, 3290, 2940, 2868, 1725, 1689, 1661, 1502, 1221;
2939, 2871, 1738, 1659,1644, 1639, 1172; H NMR (CDCl
3
) δ )
1
H NMR (CDCl
9.0 Hz), 7.40 (d, 2H, J ) 8.8 Hz), 6.88 (d, 2H, J ) 9.0 Hz),
.84 (d, 2H, J ) 8.6 Hz), 4.58 (m, 4H), 4.55 (m, 4H), 4.13-4.08
m, 2H), 4.28 (m, 2H), 4.24 (m, 2H), 4.13-4.08 (m, 2H), 3.98 (m,
H), 3.77 (s, 3H), 3.66 (s, 6H), 1.51 (m, 6H), 0.97 (d, 3H, J ) 6.7
) δ ) 176.2, 175.4,
74.8, 172.0, 171.6, 168.8, 167.9, 162.9, 161.8, 155.1, 154.6, 133.5,
33.0, 121.8, 121.4, 121.1, 120.7, 72.0, 71.6, 68.7, 53.5, 53.1, 52.7,
3
) δ ) 8.95 (m, 1H), 8.89 (m, 1H), 7.42 (d, 2H, J
9.74 (m, 1H), 9.61 (m, 1H), 9.25 (m, 2H), 7.70 (d, 1H, J ) 9.1
Hz), 7.46 (d, 1H, J ) 8.6 Hz), 7.39 (m, 2H, J ) 8.9 Hz), 6.95 (m,
1H, J ) 8.8 Hz), 6.86 (m, 1H, J ) 9.0 Hz), 6.80 (m, 2H, J ) 9.2
Hz), 4.73-4.70 (m, 4H), 4.18-3.98 (m, 8H), 3.84-3.82 (m, 2H),
)
6
(
1
3.57 (m, 1H), 1.28-1.25 (m, 24H), 1.02 (s, 6H), 0.97 (m, 6H),
13
13
Hz), 0.94 (s, 3H), 0.79 (s, 3H); C NMR (CDCl
1
1
3
0.78 (s, 6H); C NMR (CDCl
3
) δ ) 172.3, 171.9, 171.2, 169.8,
169.6, 169.4, 168.9, 165.2, 163.2, 155.8, 155.6, 155.3, 155.2, 134.5,
134.3, 134.2, 121.1, 120.7, 120.5, 120.4, 120.2, 119.8, 119.5, 72.6,
J. Org. Chem, Vol. 71, No. 20, 2006 7525