+
6
5.4, 60.2, 52.2, 52.1, 40.9, 38.6; HRMS-ESI (m/z) [M+H]
4.1.2.11 (2S,2'S)-N,N'-((2S,2'S,3R,3'R)-Piperazine-1,4-diylbis(3-
hydroxy-1-phenylbutane-4,2-diyl))bis(4-methyl-2-(5-methyl-1,3-
+
calculated for C44
H
47
N
6
O
8
: 786.3450; found: 787.3453.
dioxoisoindolin-2-yl)pentanamide) (10f): White solid; yield:
4
1
.1.2.7 N,N'-((2S,2'S,3R,3'R)-piperazine-1,4-diylbis(3-hydroxy-
o
5
5%. Mp: 103 - 105 C. IR (KBr), νmax (cm-1): 3368, 2957, 1773,
-phenylbutane-4,2-diyl))bis(2-(5-methyl-1,3-dioxoisoindolin-2-
1
o
3
1713, 1522, 1377, 1158, 1101; H NMR (400 MHz, CDCl ): δ
yl)acetamide) (10b): White solid; yield: 75%. Mp: 213 - 215 C.
-1
7.73 - 7.71 (m, 2H), 7.65 (s, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.21 -
7.13 (m, 10H), 6.45 (dd, J = 9.8, 9.6 Hz, 1H), 4.83 - 4.78 (m,
IR (KBr), νmax (cm ): 3307, 2814, 1778, 1717, 1663, 1542, 1112;
1
3
H NMR (400 MHz, CDCl ): δ 7.74 (d, J = 8.0 Hz, 2H), 7.67 (s,
2
2
1
1
H), 4.06 - 4.02 (m, 2H), 3.65 (t, J = 9.3 Hz, 2H), 2.97 - 2.87 (m,
H), 2.56 - 2.52 (m, 10H), 2.40 - 2.16 (m, 12H), 1.88 - 1.83 (m,
H), 1.74 - 1.67 m, 1H), 1.44 - 1.39 (m, 2H), 0.90 (t, J = 5.9 Hz,
2
9
3
7
3
1
1
H), 7.53 (d, J = 4.0 Hz, 2H), 7.26 - 7.17 (m, 10H), 6.22 (d, J =
.3 Hz, 2H), 4.32 - 4.22 (m, 4H), 4.03 (dd, J = 16.4, 8.2 Hz, 2H),
.64 (dd, J = 10.8, 2.9 Hz, 2H), 2.96 - 2.86 (m, 4H), 2.57 (d, J =
.9 Hz, 4H), 2.51 (s, 6H), 2.40 - 2.34 (m, 6H), 2.17 (dd, J = 12.5,
1
3
3
2H); C NMR (100 MHz, CDCl ): δ 169.2, 168.3, 145.7, 137.9,
13
134.9, 132.1, 129.4, 129.2, 128.5, 126.5, 124.2, 123.6, 65.3, 60.1,
2.9, 52.0, 51.7, 38.8, 37.3, 25.3, 23.2, 22.1, 21.4; HRMS-ESI
3
.2 Hz, 2H); C NMR (100 MHz, CDCl ): δ 168.0, 167.9, 167.8,
5
66.2, 145.7, 137.8, 134.9, 132.4, 129.4, 128.6, 126.6, 124.2,
23.6, 65.2, 60.2, 51.9, 41.0, 38.9, 22.1; HRMS-ESI (m/z)
+
+
(m/z) [M+H] calculated for C54
67 6 8
H N O : 927.5015; found:
+
+
8
927.5014.
[M+H] calculated for C46
51
H N
6
O
: 815.3763; found: 815.3763.
4
.1.2.12
hydroxy-3-((2S,3R)-3-methyl-2-(5-methyl-1,3-dioxoisoindolin-
-yl)pentanamido)-4-phenylbutyl)piperazin-1-yl)-1-phenylbutan-
2-yl)-3-methyl-2-(5-methyl-1,3-dioxoisoindolin-2-
yl)pentanamide (10g): White solid; yield: 62%. Mp: 96 - 98 C.
(2S,3S)-N-((2S,3R)-3-Hydroxy-4-(4-((2R,3S)-2-
4
.1.2.8 (2S,2'S)-N,N'-((2S,2'S,3R,3'R)-Piperazine-1,4-diylbis(3-
hydroxy-1-phenylbutane-4,2-diyl))bis(2-(1,3-dioxoisoindolin-2-
2
yl)propanamide) (10c): White solid; yield: 56%. Mp: 148 - 150
o
-1
C. IR (KBr), νmax (cm ): 3289, 2922, 1778, 1774, 1709, 1668,
o
1
1
7
4
9
=
534, 1019; H NMR (400 MHz, CDCl
3
): δ 7.84 - 7.83 (m, 4H),
-1
IR (KBr), νmax (cm ): 3365, 2929, 2363, 1772, 1709, 1524, 1377,
.75 - 7.73 (m, 4H), 7.23 - 7.19 (m, 12H), 6.53 - 6.41 (m, 2H),
.84 (d, J = 6.9 Hz, 2H), 4.12 - 4.09 (m, 2H), 3.75 (dd, J = 17.6,
.3 Hz, 2H), 2.94 - 2.88 (m, 4H), 2.77 - 2.36(m, 12H), 1.61 (d, J
1
1
7
072; H NMR (400 MHz, CDCl
.63 (s, 2H), 7.53 (d, J = 7.4 Hz, 2H), 7.21 - 6.96 (m, 12H), 4.38
3
): δ 7.70 (d, J = 7.5 Hz, 2H),
13
- 4.33 (m, 2H), 4.03 (dd, J = 15.9, 7.9 Hz, 2H), 3.65 (dd, J = 9.2,
3
6.4 Hz, 6H); C NMR (100 MHz, CDCl ): δ 169.0, 167.8,
4
6
.3 Hz, 2H), 2.93 (t, J = 7.9 Hz, 4H), 2.59 (s, br, 3H), 2.52 (s,
H), 2.42 (s, br, 3H), 2.20 - 2.02 (m, 10H), 1.30 - 1.25 (m, 4H),
1
6
62.7, 137.8, 134.5, 134.3, 131.9, 129.4, 128.6, 126.6, 123.6,
5.6, 65.5, 60.3, 52.3, 49.3, 49.0, 38.6, 36.6, 31.5, 27.1, 15.3;
13
+
+
1.0 – 0.92 (m, 2H), 0.83 - 0.75 (m, 12H); C NMR (100 MHz,
CDCl ): δ 168.8, 168.4, 145.9, 138.0, 135.0, 131.8, 129.3, 128.4,
26.4, 124.2, 123.6, 65.9, 61.5, 60.4, 52.1, 38.5, 32.6, 25.4, 22.2,
HRMS-ESI (m/z) [M+H] calculated for C46
found: 815.3768.
51 6 8
H N O : 815.3763;
3
1
+
4.1.2.9 (2S,2'S)-N,N'-((2S,2'S,3R,3'R)-Piperazine-1,4-diylbis(3-
15.8, 10.2; HRMS-ESI (m/z) [M+H]
C H N O : 927.5015; found: 927.5062.
calculated for
+
8
hydroxy-1-phenylbutane-4,2-diyl))bis(2-(5-methyl-1,3-
54
67
6
dioxoisoindolin-2-yl)propanamide) (10d): White solid; yield:
o
-1
4.1.2.13 Di-tert-butyl ((((2S,2'S,3R,3'R)-piperazine-1,4-diylbis(3-
hydroxy-1-phenylbutane-4,2-diyl))bis(azanediyl))bis(2-
5
1
2
7%. Mp: 169 - 171 C. IR (KBr), νmax (cm ): 3377, 2926, 1710,
1
526, 1101; H NMR (400 MHz, CDCl
3
): δ 7.67 (s, 2H), 7.59 (s,
oxoethane-2,1-diyl))dicarbamate (11a): White solid; yield: 60%.
H), 7.48 (s, 2H), 7.17 (s, 10H), 6.45 (s, 2H), 4.79 (s, 2H), 4.45
o
-1
Mp: 116 - 118 C. IR (KBr), νmax (cm ): 3407, 2926, 1685, 1546,
(
–
s, 2H), 4.05 (s, 2H), 3.65 (s, 2H), 2.86 (s, 4H), 2.60 (s, 6H), 2.47
1
13
1165, 1030; H NMR (400 MHz, CDCl
3
): δ 7.28 - 7.19 (m, 12H),
2.21 (m, 12H), 1.59 (d, J = 6.0 Hz, 6H); C NMR (100 MHz,
): δ 169.1, 167.9, 145.6, 137.9, 134.8, 132.3, 129.4, 128.5,
26.5, 124.1, 123.5, 65.4, 60.2, 52.6, 52.1, 49.1, 38.7, 29.7, 22.1,
6.51 (d, J = 9.3 Hz, 2H), 5.13 (s, br, 2H), 4.05 (dd, J = 16.8, 8.1
CDCl
3
Hz, 2H), 3.72 - 3.62 (m, 6H), 2.90 (d, J = 7.7 Hz, 4H), 2.58 (s, br,
4H), 2.42 - 2.36 (m, 2H), 2.20 (d, J = 12.2 Hz, 1H), 1.43 (s,
1
1
8
+
+
5.2; HRMS-ESI (m/z) [M+H] calculated for C48
43.4076; found: 843.4078.
55 6 8
H N O :
1
3
1
1
8H); C NMR (100 MHz, CDCl
3
): δ 169.6, 156.1, 137.8, 129.4,
28.6, 126.6, 80.2, 65.5, 60.0, 51.7, 44.4, 38.7, 28.4, 22.5;
HRMS-ESI (m/z) [M+H] calculated for C H N O : 727.4389;
38 59 6 8
+
+
4.1.2.10 (2S,2'S)-N,N'-((2S,2'S,3R,3'R)-Piperazine-1,4-diylbis(3-
hydroxy-1-phenylbutane-4,2-diyl))bis(3-methyl-2-(5-methyl-1,3-
found: 727.4377.
dioxoisoindolin-2-yl)butanamide) (10e): White solid; yield: 48%.
o
-1
4.1.2.14 Di-tert-butyl((2S,2'S)-(((2S,2'S,3R,3'R)-piperazine-1,4-
diylbis(3-hydroxy-1-phenylbutane-4,2-diyl))bis(azanediyl))bis(1-
oxopropane-2,1-diyl))dicarbamate (11b): White solid; yield:
Mp: 239 - 241 C. IR (KBr), νmax (cm ): 3281, 2953, 1721, 1635,
1
1
7
4
3
536, 1007; H NMR (400 MHz, CDCl ): δ 7.73 – 7.70 (m, 2H),
.64 – 7.63 (m, 2H), 7.54 – 7.53 (m, 2H), 7.22 - 6.96 (m, 12H),
.29 – 4.25 (m, 2H), 4.07 – 4.01 (m, 2H), 3.66 (dd, J = 13.9, 7.7
o
-1
5
1
7
9%. Mp: 112 - 114 C. IR (KBr), νmax (cm ): 3319, 2979, 1714,
1
656, 1521, 1167, 1021; H NMR (400 MHz, CDCl
3
): δ 7.28 -
Hz, 2H), 2.96 - 2.85 (m, 4H), 2.79 - 2.71(m, 2H), 2.52 (s, 6H),
.16 (m, 10H), 6.57 (d, J = 9.1 Hz, 2H), 4.77 (s, br, 2H), 4.02
2
6
1
1
3
.43 - 2.06 (m, 12H), 1.03 (d, J = 6.6 Hz, 2H), 0.89 – 0.86 (m,
H), 0.80 – 0.78 (m, 6H); C NMR (100 MHz, CDCl ): δ 168.7,
3
1
3
(dd, J = 14.3, 7.3 Hz, 2H), 3.66 (d, J = 10.7 Hz, 2H), 2.95 - 2.88
m, 4H), 2.54 (s, br, 4H), 2.41 - 2.36 (m, 4H), 2.15 (d, J = 12.1
(
68.4, 168.3, 145.9, 138.0, 135.0, 131.8, 129.3, 129.2, 128.8,
28.4, 128.2, 126.4, 124.2, 123.6, 66.0, 62.8, 60.4, 52.1, 51.4,
8.8, 38.5, 27.5, 27.2, 22.2, 20.1, 19.9, 19.6, 19.5; HRMS-ESI
13
Hz, 2H), 1.43 (s, 18H), 1.20 (d, J = 7.1 Hz, 6H); C NMR (100
MHz, CDCl ): δ 172.4, 155.3, 138.1, 129.4, 128.4, 126.5, 80.3,
65.5, 59.9, 51.0, 39.1, 28.3, 18.3; HRMS-ESI (m/z) [M+H]
3
+
+
+
(m/z) [M+H] calculated for C52
63 6 8
H N O : 899.4702; found:
+
63 6 8
calculated for C40H N O : 755.4702; found: 755.4701.
899.4677.