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J. Yao et al. / European Journal of Medicinal Chemistry 50 (2012) 196e208
4H), 6.70 (d, 2H, J ¼ 8.44 Hz), 5.00 (m, 1H), 4.81 (m, 1H), 4.75 (m,
1H), 4.65 (m, 1H), 4.55 (m, 1H), 4.36 (m, 1H), 4.25 (m, 1H), 4.03 (t,
2H, J ¼ 6.45 Hz), 4.01 (m, 2H), 3.92 (m, 1H), 3.70 (m, 2H), 3.03 (m,
2H), 2.89 (m,1H), 2.60 (m, 3H), 2.30e2.40 (m, 9H), 2.21 (m,1H), 2.13
(m, 2H), 1.60e2.00 (m, 12H), 1.40e1.50 (m, 6H), 1.29 (d, 3H,
J ¼ 5.67 Hz), 0.97 (t, 3H, J ¼ 7.19 Hz). 13C NMR (CD3OD, 500 MHz):
174.79, 174.64, 173.88, 173.53, 172.08, 171.37, 170.36 (7 ꢂ C]O);
160.47, 156.80, 145.45, 141.96, 141.79, 139.19, 133.91, 132.82, 130.53,
129.87, 129.19, 128.90, 128.44, 128.02, 127.80, 126.97, 116.28, 116.00
(36 ꢂ AreC); 69.16, 68.71, 64.25, 61.01, 58.10, 54.46, 54.23, 52.31,
51.68, 51.59, 40.68, 38.43, 35.02, 33.62, 33.16, 32.77, 30.12, 29.39,
28.38, 26.97, 25.05, 23.50, 23.01, 21.29, 20.15, 14.34 (30 ꢂ Alkyl-C).
171.75, 170.10 (7 ꢂ C]O); 160.44, 156.72, 145.38, 141.87, 141.80,
139.24, 133.87, 133.16, 130.44, 129.88, 129.15, 128.89, 128.45, 128.37,
127.77, 126.95, 116.28, 116.01 (36 ꢂ AreC); 69.15, 63.99, 61.04,
58.04, 57.02, 53.87, 51.99, 51.86, 51.39, 40.86, 38.71, 33.76, 33.45,
33.01, 32.72, 32.30, 31.87, 29.38, 27.62, 27.29, 27.21, 26.70, 23.62,
23.49, 21.30, 20.25, 18.74, 14.35 (31 ꢂ Alkyl-C). MS (ESIþ) m/z:
1070.67 (M þ Hþ, 100%). Anal. calcd for C74H95N9O15S2: C, 62.85; H,
6.72; N, 8.92; Found: C, 63.02; H, 6.70; N, 8.90.
6.1.22. Cyclolipohexapeptide amine p-tosylate 28l
White solid (Yield 96.30%), Mp: 193e197 ꢀC. 1H NMR (CD3OD,
500 MHz)
d
: 7.96 (d, 2H, J ¼ 8.29 Hz), 7.78 (d, 2H, J ¼ 8.29 Hz), 7.70
MS (ESIþ) m/z: 1072.99 (M
þ
Hþ, 100%). Anal. calcd for
(m, 8H), 7.60 (d, 2H, J ¼ 8.62 Hz), 7.23 (d, 4H, J ¼ 7.96 Hz), 7.00 (m,
4H), 6.70 (d, 2H, J ¼ 8.44 Hz), 4.80 (m, 2H), 4.55 (m, 1H), 4.50 (m,
2H), 4.23 (m, 1H), 4.02 (t, 2H, J ¼ 6.44 Hz), 3.99 (m, 1H), 3.60e3.95
(m, 5H), 2.80e3.05 (m, 3H), 2.40e2.60 (m, 3H), 2.20e2.38 (m, 10H),
1.90e2.20 (m, 7H), 1.60e1.85 (m, 7H), 1.30e1.50 (m, 10H), 1.08 (d,
3H, J ¼ 6.78 Hz),1.00 (d, 3H, J ¼ 6.24 Hz), 0.92 (t, 3H, J ¼ 6.82 Hz). 13C
NMR(CD3OD, 500 MHz): 174.82, 174.75, 174.43, 173.40, 171.93,
171.78, 170.12 (7 ꢂ C]O); 160.48, 156.75, 145.37, 141.95, 141.80,
139.27, 133.92, 133.14, 130.44, 129.88, 129.14, 128.91, 128.45, 128.37,
127.80, 126.98, 116.29, 116.03 (36 ꢂ AreC); 69.19, 64.05, 61.05,
58.04, 57.03, 53.87, 51.99, 51.86, 51.39, 40.88, 38.71, 33.76, 33.45,
32.96, 32.72, 32.30, 31.87, 30.44, 30.18, 27.65, 27.31, 27.25, 27.14,
26.70, 23.64, 21.29, 20.27,18.75,14.37 (33 ꢂ Alkyl-C). MS (ESIþ) m/z:
1098.90 (M þ Hþ, 100%), 1121.02 (M þ Naþ, 75%). Anal. calcd for
C76H99N9O15S2: C, 63.29; H, 6.87; N, 8.74; Found: C, 63.48; H, 6.86;
N, 8.71.
C73H93N9O16S2: C, 61.91; H, 6.57; N, 8.90; Found: C, 62.10; H, 6.55;
N, 8.88.
6.1.19. Cyclolipohexapeptide amine p-tosylate 28i
White solid (Yield 93.72%), Mp: 220e222 ꢀC. 1H NMR (CD3OD,
500 MHz)
d
: 7.97 (d, 2H, J ¼ 8.42 Hz), 7.78 (d, 2H, J ¼ 8.42 Hz), 7.71
(m, 8H), 7.60 (d, 2H, J ¼ 8.76 Hz), 7.23 (d, 4H, J ¼ 7.91 Hz), 7.00 (m,
4H), 6.70 (d, 2H, J ¼ 8.48 Hz), 5.00 (m, 1H), 4.81 (m, 1H), 4.75 (m,
1H), 4.65 (m, 1H), 4.55 (m, 1H), 4.36 (m, 1H), 4.25 (m, 1H), 4.02 (t,
2H, J ¼ 6.49 Hz), 4.00 (m, 2H), 3.92 (m, 1H), 3.69 (m, 2H), 3.03 (m,
2H), 2.89 (m,1H), 2.60 (m, 3H), 2.30e2.40 (m, 9H), 2.21 (m,1H), 2.11
(m, 2H), 1.60e2.00 (m, 12H), 1.51 (m, 3H), 1.30e1.45 (m, 7H), 1.29 (d,
3H, J ¼ 6.13 Hz), 0.92 (t, 3H, J ¼ 6.96 Hz). 13C NMR(CD3OD,
500 MHz): 174.78, 174.65, 173.87, 173.53, 172.09, 171.38, 170.37
(7 ꢂ C]O); 160.48, 156.82, 145.47, 141.99, 141.78, 139.20, 133.93,
132.83, 130.52, 129.86, 129.18, 128.91, 128.44, 128.03, 127.81, 126.98,
116.29, 116.03 (36 ꢂ AreC); 69.20, 68.74, 64.26, 61.04, 58.11, 54.49,
54.22, 52.31, 51.70, 51.61, 40.70, 38.45, 35.07, 33.62, 33.16, 32.95,
32.78, 30.43, 30.17, 28.39, 27.13, 27.00, 25.05, 23.62, 23.03, 21.28,
20.15, 14.35 (32 ꢂ Alkyl-C). MS (ESIþ) m/z: 1100.94 (M þ Hþ, 80%),
1123.01 (M þ Naþ, 100%). Anal. calcd for C75H97N9O16S2: C, 62.37; H,
6.72; N, 8.73; Found: C, 62.56; H, 6.70; N, 8.70.
6.1.23. Cyclolipohexapeptide amine p-tosylate 29a
White solid (Yield 96.40%), Mp: 167e169 ꢀC. 1H NMR (CD3OD,
500 MHz)
d
: 8.35 (s, 1H), 7.84 (m, 3H), 7.71 (d, 4H, J ¼ 8.12 Hz), 7.22
(m, 6H), 7.00 (d, 2H, J ¼ 8.48 Hz), 6.69 (d, 2H, J ¼ 8.48 Hz), 4.95 (m,
1H), 4.75 (m, 1H), 4.66 (m, 1H), 4.54 (m, 1H), 4.33 (m, 1H), 4.25 (m,
1H), 4.11 (t, 2H, J ¼ 6.42 Hz), 4.05 (m, 2H), 3.90 (m, 1H), 3.85 (m, 1H),
3.63 (m, 2H), 3.05 (m, 2H), 2.90 (m, 1H), 2.47e2.70 (m, 3H),
2.25e2.40 (m, 10H), 2.21 (m, 1H), 1.65e2.10 (m, 14H), 1.50 (m, 2H),
1.42 (m, 2H), 1.33 (m, 4H), 1.28 (d, 3H, J ¼ 6.13 Hz), 0.92 (t, 3H,
J ¼ 6.96 Hz). 13C NMR(CD3OD, 500 MHz): 175.07, 174.74, 173.97,
173.72, 172.02, 171.08, 170.70 (7 ꢂ C]O); 160.23, 156.75, 143.50,
141.79, 138.07, 132.87, 131.55, 130.56, 129.87, 129.28, 128.92, 128.13,
126.95, 125.45, 120.99, 116.26, 107.56 (28 ꢂ AreC); 69.26, 68.77,
64.33, 60.86, 58.18, 54.36, 54.10, 52.40, 51.89, 51.25, 40.77, 38.68,
35.11, 33.67, 32.93, 32.84, 30.45, 30.40, 30.30, 30.15, 27.29, 27.22,
27.16, 24.51, 24.40, 23.62, 21.29, 20.24, 14.37 (31 ꢂ Alkyl-C). MS
(ESIþ) m/z: 984.75 (M þ Hþ, 70%), 1006.99 (M þ Naþ, 100%). Anal.
calcd for C66H89N9O16S2: C, 59.68; H, 6.71; N, 9.50; Found: C, 59.86;
H, 6.70; N, 9.48.
6.1.20. Cyclolipohexapeptide amine p-tosylate 28j
White solid (Yield 95.85%), Mp: 179e182 ꢀC. 1H NMR (CD3OD,
500 MHz)
d
: 7.95 (d, 2H, J ¼ 8.42 Hz), 7.77 (d, 2H, J ¼ 8.42 Hz), 7.69
(m, 8H), 7.59 (d, 2H, J ¼ 8.77 Hz), 7.23 (d, 4H, J ¼ 7.94 Hz), 7.00 (m,
4H), 6.70 (d, 2H, J ¼ 8.50 Hz), 4.80 (m, 2H), 4.55 (m, 1H), 4.50 (m,
2H), 4.23 (m, 1H), 4.03 (m, 1H), 3.96 (t, 2H, J ¼ 6.47 Hz), 3.60e3.95
(m, 5H), 2.80e3.05 (m, 3H), 2.40e2.60 (m, 3H), 2.20e2.38 (m, 10H),
1.90e2.20 (m, 7H), 1.60e1.85 (m, 7H), 1.43 (m, 2H), 1.06 (m, 6H),
1.00 (d, 3H, J ¼ 6.58 Hz). 13C NMR(CD3OD, 500 MHz): 174.80, 174.74,
174.39, 173.35, 171.90, 171.75, 170.10 (7 ꢂ C]O); 160.45, 156.72,
145.36, 141.87, 141.80, 139.19, 133.87, 133.16, 130.43, 129.88, 129.15,
128.89, 128.45, 128.37, 127.77, 126.96, 116.28, 116.01 (36 ꢂ AreC);
70.70, 63.99, 61.04, 58.04, 57.03, 53.87, 51.99, 51.86, 51.39, 40.86,
38.71, 33.76, 33.45, 33.01, 32.72, 32.30, 31.87, 27.62, 27.28, 27.21,
26.70, 23.67, 23.62, 21.30, 20.25, 18.74, 10.82 (29 ꢂ Alkyl-C). MS
(ESIþ) m/z: 1042.41 (M þ Hþ, 75%), 1064.47 (M þ Naþ, 100%). Anal.
calcd for C72H91N9O15S2: C, 62.38; H, 6.57; N, 9.10; Found: C, 62.56;
H, 6.55; N, 9.07.
6.1.24. Cyclolipohexapeptide amine p-tosylate 29b
White solid (Yield 93.00%), Mp: 162e165 ꢀC. 1H NMR (CD3OD,
500 MHz)
d: 8.35 (s, 1H), 7.84 (m, 3H), 7.71 (d, 4H, J ¼ 8.10 Hz), 7.22
(m, 6H), 7.00 (d, 2H, J ¼ 8.43 Hz), 6.69 (d, 2H, J ¼ 8.43 Hz), 4.95 (m,
1H), 4.78 (m, 1H), 4.66 (m, 1H), 4.56 (m, 1H), 4.33 (m, 1H), 4.25 (m,
1H), 4.11 (t, 2H, J ¼ 6.43 Hz), 4.05 (m, 2H), 3.90 (m, 1H), 3.85 (m, 1H),
3.63 (m, 2H), 3.05 (m, 2H), 2.93 (m, 1H), 2.47e2.70 (m, 3H),
2.25e2.40 (m, 10H), 2.21 (m, 1H), 1.65e2.10 (m, 14H), 1.50 (m, 2H),
1.30e1.45 (m, 8H), 1.28 (d, 3H, J ¼ 6.03 Hz), 0.91 (t, 3H, J ¼ 6.96 Hz).
13C NMR(CD3OD, 500 MHz): 175.07, 174.75, 173.97, 173.72, 172.03,
171.08, 170.70 (7 ꢂ C]O); 160.23, 156.76, 143.54, 141.75, 138.07,
132.87, 131.55, 130.56, 129.85, 129.28, 128.92, 128.13, 126.95, 125.45,
120.99, 116.26, 107.57 (28 ꢂ AreC); 69.26, 68.77, 64.33, 60.86, 58.17,
54.36, 54.10, 52.41, 51.89, 51.23, 40.80, 38.68, 35.09, 33.67, 32.94,
32.84, 30.44, 30.40, 30.34, 30.30, 27.29, 27.23, 24.54, 24.43, 23.66,
21.29, 20.23, 14.38 (32 ꢂ Alkyl-C). MS (ESIþ) m/z: 999.07 (M þ Hþ,
6.1.21. Cyclolipohexapeptide amine p-tosylate 28k
White solid (Yield 97.02%), Mp: 178e181 ꢀC. 1H NMR (CD3OD,
500 MHz)
d
: 7.95 (d, 2H, J ¼ 8.38 Hz), 7.77 (d, 2H, J ¼ 8.38 Hz), 7.69
(m, 8H), 7.59 (d, 2H, J ¼ 8.77 Hz), 7.23 (d, 4H, J ¼ 7.92 Hz), 6.99 (m,
4H), 6.70 (d, 2H, J ¼ 8.48 Hz), 4.80 (m, 2H), 4.55 (m, 1H), 4.50 (m,
2H), 4.23 (m, 1H), 4.03 (m, 1H), 3.98 (t, 2H, J ¼ 6.45 Hz), 3.60e3.95
(m, 5H), 2.80e3.05 (m, 3H), 2.40e2.60 (m, 3H), 2.20e2.38 (m, 10H),
1.90e2.20 (m, 7H),1.60e1.85 (m, 7H),1.35e1.50 (m, 6H),1.08 (d, 3H,
J ¼ 6.58 Hz), 1.00 (d, 3H, J ¼ 6.56 Hz), 0.96 (t, 3H, J ¼ 7.17 Hz). 13C
NMR(CD3OD, 500 MHz): 174.80, 174.74, 174.39, 173.35, 171.90,