J. Yao et al. / Tetrahedron 68 (2012) 3074e3085
3083
cyclic lipopeptide 29A1 (340 mg, yield 73.5%, six steps) as white
solid. MS (ESIþ) m/z: 1254.95 (MþNaþ, 100%). Anal. calcd for
C67H81N11O12: C, 65.31; H, 6.58; N, 12.51; found: C, 65.47; H, 6.57; N,
61.07, 58.05, 56.98, 53.92, 52.48, 52.36, 51.23, 40.09, 38.60, 34.20,
33.00, 32.74, 31.91, 31.52, 30.39,30.05, 29.37, 26.83, 26.75, 26.47, 25.94,
25.02, 23.66, 21.30, 20.15, 18.78, 14.34 (31ꢂ Alkyl-C). MS (ESIþ) m/z:
1070.81 (MþHþ, 100%). Anal. calcd for C74H95N9O15S2: C, 62.85; H,
6.72; N, 8.92; found: C, 63.02; H, 6.70; N, 8.89.
12.46. The synthetic procedure for cyclic lipopeptides 29A2e8
,
29B1e4, 29C1e4, and 29D1e4 was similar to the preparation of 29A1.39
4.1.12. Macrocyclic lipopeptide amine p-tosylate (30a). A solution of
cyclic lipopeptide 29A1 (160 mg, 0.13 mmol) in EtOH (25 mL) was
added PTSA,H2O (60 mg, 0.32 mmol) and 10% PdeC (90 mg). The
reaction mixture was stirred at room temperature under H2 for
24 h. After filtration, the solvent was removed under reduced
pressure. The residue was purified by Sephadex column chroma-
tography (MeOH) to afford the target compound 30a (176 mg, yield
95.7%) as white solid. Mp: 228e231 ꢀC. 1H NMR (CD3OD, 500 MHz)
4.1.15. Macrocyclic lipopeptide amine p-tosylate (30d). White solid
(Yield 99.2%), Mp: 230e233 ꢀC. 1H NMR (CD3OD, 500 MHz)
d: 7.96 (d,
2H, J¼8.38 Hz), 7.77 (d, 2H, J¼8.38 Hz), 7.71 (m, 8H), 7.60 (d, 2H,
J¼8.69 Hz), 7.23 (d, 4H, J¼7.94 Hz), 7.00 (m, 4H), 6.70 (d, 2H,
J¼8.47 Hz), 4.81 (m, 2H), 4.55 (m,1H), 4.49 (m, 2H), 4.22 (m,1H), 4.03
(m, 1H), 4.01 (t, 2H, J¼6.45 Hz), 3.95e3.60 (m, 5H), 3.03 (m, 1H), 2.91
(m, 2H), 2.58 (m, 2H), 2.49 (m,1H), 2.36e2.25 (m,10H), 2.25e1.90 (m,
7H),1.87e1.70 (m, 7H), 1.50e1.25 (m, 8H),1.08 (d, 3H, J¼6.81 Hz),1.00
(d, 3H, J¼6.62 Hz), 0.91 (t, 3H, J¼6.89Hz).13C NMR(CD3OD, 500 MHz):
174.78,174.42,173.40,171.93,171.46,170.11 (7ꢂ C]O); 160.46,156.74,
145.38, 141.92, 141.84, 139.23, 133.92, 133.12, 130.44, 129.89, 129.14,
128.91,128.45,128.37,127.78,126.97,116.27,116.00 (36ꢂ AreC); 69.16,
63.98, 61.07, 58.05, 56.97, 53.92, 52.48, 52.36, 51.29, 40.09, 38.60,
33.45, 33.01, 31.91, 31.52, 30.47, 30.42, 30.37, 27.30, 27.24, 27.17, 26.11,
25.65, 25.01, 23.68, 21.29, 20.15, 18.80, 14.39 (33ꢂ Alkyl-C). MS (ESIþ)
m/z: 1098.98 (MþHþ, 100%). Anal. calcd for C76H99N9O15S2: C, 63.29;
H, 6.87; N, 8.74; found: C, 63.47; H, 6.85; N, 8.71.
d: 7.96 (d, 2H, J¼8.41 Hz), 7.78 (d, 2H, J¼8.41 Hz), 7.72 (m, 8H), 7.61
(d, 2H, J¼8.76 Hz), 7.23 (d, 4H, J¼7.93 Hz), 7.01 (m, 4H), 6.70 (d, 2H,
J¼8.46 Hz), 4.96 (m, 1H), 4.75 (m, 1H), 4.66 (m, 1H), 4.55 (m, 1H),
4.27 (m, 2H), 4.02 (t, 2H, J¼6.39 Hz), 4.01 (m, 2H), 3.95 (m, 1H), 3.82
(m, 1H), 3.66 (m, 2H), 3.03 (m, 2H), 2.91 (m, 1H), 2.60 (m, 3H),
2.20e2.12 (m, 10H), 2.11e1.90 (m, 7H), 1.90e1.70 (m, 7H), 1.35e1.48
(m, 6H), 1.29 (d, 3H, J¼6.06 Hz), 0.94 (t, 3H, J¼7.19 Hz). 13C NMR
(CD3OD, 500 MHz): 174.97, 174.74, 174.01, 173.73, 172.02, 171.06,
170.35 (7ꢂ C]O); 160.49, 156.80, 145.43, 141.96, 141.72, 139.22,
133.90, 132.87, 130.55, 129.83, 129.19, 128.91, 128.45, 128.03, 127.79,
126.97, 116.28, 116.03 (36ꢂ AreC); 69.20, 68.83, 64.35, 60.94, 58.17,
54.90, 54.21, 52.32, 51.90, 51.37, 40.77, 38.47, 34.75, 33.59, 32.75,
30.40, 30.30, 27.31, 27.24, 26.84, 25.11, 24.45, 24.41, 23.64, 21.28,
20.20, 14.32 (30ꢂ Alkyl-C). MS (ESIþ) m/z: 1072.84 (MþHþ, 100%).
Anal. calcd for C73H93N9O16S2: C, 61.91; H, 6.57; N, 8.90; found: C,
62.08; H, 6.55; N, 8.87.The synthetic procedure for p-tosylate cyclic
lipopeptide amines 30beh, 31aed, 32aed, and 33aed was similar
4.1.16. Macrocyclic lipopeptide amine p-tosylate (30e). White solid
(Yield 91.7%), Mp: 221e223 ꢀC. 1H NMR (CD3OD, 500 MHz)
d: 7.97 (d,
2H, J¼8.37 Hz), 7.78 (d, 2H, J¼8.37 Hz), 7.71 (m, 8H), 7.60 (d, 2H,
J¼8.74 Hz), 7.22 (d, 4H, J¼7.96 Hz), 7.00 (m, 4H), 6.70 (d, 2H,
J¼8.45 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, J¼6.40 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), 2.40e2.30(m, 9H), 2.21 (m,1H), 2.11 (m, 2H), 2.00e1.60 (m,12H),
1.51 (m, 3H), 1.380 (m, 5H), 1.29 (d, 3H, J¼6.14 Hz), 0.94 (t, 3H,
J¼7.08 Hz).13C NMR (CD3OD, 500 MHz): 174.78,174.65,173.87,173.52,
172.08,171.39,170.35 (7ꢂ C]O); 160.48,156.81,145.45,141.97,141.78,
139.20, 133.92, 132.83, 130.53, 129.87, 129.18, 128.91, 128.44, 128.03,
127.81, 126.97, 116.29, 116.03 (36ꢂ AreC); 69.19, 68.72, 64.26, 61.03,
58.11, 54.56, 54.22, 52.34, 51.71, 51.60, 40.70, 38.45, 35.07, 33.65, 33.16,
32.75, 30.48, 30.39, 28.38, 26.97, 26.84, 25.08, 23.64, 23.02, 21.29,
20.15, 14.32 (31ꢂ Alkyl-C). MS (ESIþ) m/z: 1086.87 (MþHþ, 50%),
1108.95 (MþNaþ, 100%). Anal. calcd for C74H95N9O16S2: C, 62.14; H,
6.65; N,8.82; found: C, 62.31; H, 6.63; N, 8.79.
to the preparation of the compound 30a except using 29A2e8
29B1e4, 29C1e4, and 27D1e4 instead of 29A1, respectively.
,
4.1.13. Macrocyclic lipopeptide amine p-tosylate (30b). White solid
(Yield 93.4%), Mp: 205e208 ꢀC. 1H NMR (CD3OD, 500 MHz)
: 7.96
d
(d, 2H, J¼8.48 Hz), 7.77 (d, 2H, J¼8.48 Hz), 7.71 (m, 8H), 7.60 (d, 2H,
J¼8.80 Hz), 7.23 (d, 4H, J¼7.95 Hz), 7.00 (m, 4H), 6.70 (d, 2H,
J¼8.49 Hz), 4.95 (m, 1H), 4.75 (m, 1H), 4.66 (m, 1H), 4.55 (m, 1H),
4.27 (m, 2H), 4.02 (t, 2H, J¼6.47 Hz), 4.01 (m, 1H), 3.98 (m, 1H), 3.96
(m, 1H), 3.82 (m, 1H), 3.66 (m, 2H), 3.02 (m, 2H), 2.91 (m, 1H), 2.60
(m, 3H), 2.20e2.12 (m, 10H), 2.11e1.90 (m, 7H), 1.90e1.70 (m, 7H),
1.48e1.35 (m, 10H), 1.27 (d, 3H, J¼6.10 Hz), 0.92 (t, 3H, J¼7.14 Hz).
13C NMR (CD3OD, 500 MHz): 174.97, 174.74, 174.01, 173.73, 172.06,
171.08, 170.34 (7ꢂ C]O); 160.48, 156.80, 145.38, 141.96, 141.78,
139.21, 133.88, 132.87, 130.56, 129.86, 129.19, 128.91, 128.45, 128.03,
127.79, 126.97, 116.28, 116.04 (36ꢂ AreC); 69.20, 68.82, 64.36,
60.93, 58.18, 54.92, 54.16, 52.33, 51.88, 51.37, 40.77, 38.44, 40.74,
38.45, 34.75, 34.44, 32.95, 30.46, 30.42, 30.35, 27.31, 27.24, 27.17,
26.60, 25.99, 24.51, 24.38, 23.67, 21.29, 20.24, 14.34 (32ꢂ Alkyl-C).
MS (ESIþ) m/z: 1072.84 (MþHþ, 100%). MS (ESIþ) m/z: 1100.85
(MþHþ, 100%). Anal. calcd for C75H97N9O16S2: C,62.37; H, 6.72; N,
8.73; found: C, 62.52; H, 6.70; N, 8.70.
4.1.17. Macrocyclic lipopeptide amine p-tosylate (30f). White solid
(Yield 96.5%), Mp: 206e210 ꢀC. 1H NMR (CD3OD, 500 MHz)
d: 7.97
(d, 2H, J¼8.27 Hz), 7.79 (d, 2H, J¼8.27 Hz), 7.71 (m, 8H), 7.61 (d, 2H,
J¼8.60 Hz), 7.23 (d, 4H, J¼7.77 Hz), 7.01 (m, 4H), 6.70 (d, 2H,
J¼8.40 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), 4.01 (t, 2H, J¼6.45 Hz), 3.99
(m, 2H), 3.92 (m, 1H), 3.69 (m, 2H), 3.03 (m, 2H), 2.89 (m, 1H), 2.60
(m, 3H), 2.40e2.30 (m, 9H), 2.21 (m, 1H), 2.11 (m, 2H), 2.00e1.60
(m, 12H), 1.51 (m, 3H), 1.45e1.30 (m, 9H), 1.28 (d, 3H, J¼6.12 Hz),
0.92 (t, 3H, J¼6.95 Hz). 13C NMR(CD3OD, 500 MHz): 174.79, 174.65,
173.89, 173.54, 172.12, 171.37, 171.25 (7ꢂ C]O); 160.49, 156.84,
145.46, 141.99, 141.80, 139.20, 133.92, 132.82, 130.54, 129.88, 129.21,
128.92, 128.46, 128.05, 127.82, 126.98, 116.29, 116.02 (36ꢂ AreC);
69.17, 68.65, 64.26, 62.88, 58.11, 54.50, 54.23, 52.34, 51.72, 51.60,
40.70, 38.45, 35.05, 33.64, 33.16, 32.98, 32.85, 32.78, 30.44, 30.38,
28.41, 27.18, 27.01, 25.10, 23.69, 23.03, 21.30, 20.15, 14.37 (33ꢂ Al-
kyl-C). MS (ESIþ) m/z: 1114.89 (MþHþ, 80%), 1137.08 (MþNaþ,
100%). Anal. calcd for C76H99N9O16S2: C, 62.59; H, 6.79; N, 8.65;
found: C, 62.76; H, 6.77; N, 8.62.
4.1.14. Macrocyclic lipopeptide amine p-tosylate (30c). White solid
(Yield 95.5%), Mp: 193e196 ꢀC. 1H NMR (CD3OD, 500 MHz)
d: 7.95 (d,
2H, J¼8.42 Hz), 7.76 (d, 2H, J¼8.42 Hz), 7.69 (m, 8H), 7.59 (d, 2H,
J¼8.73 Hz), 7.23 (d, 4H, J¼7.93 Hz), 6.99 (m, 4H), 6.70 (d, 2H,
J¼8.46 Hz), 4.82(m, 2H), 4.65e4.40(m, 3H), 4.22(m,1H), 4.03(m,1H),
4.00 (t, 2H, J¼6.49 Hz), 3.95e3.55 (m, 5H), 3.03 (m, 1H), 2.91 (m, 2H),
2.58 (m, 2H), 2.49 (m, 1H), 2.36e2.25 (m, 10H), 2.25e1.90 (m, 7H),
1.87e1.70 (m, 7H), 1.50e1.30 (m, 6H), 1.08 (d, 3H, J¼6.80 Hz), 1.00 (d,
3H, J¼6.59 Hz), 0.93 (t, 3H, J¼6.97 Hz). 13C NMR (CD3OD, 500 MHz):
174.76, 174.39, 173.38, 171.91, 171.45, 170.12 (7ꢂ C]O); 160.44,156.72,
145.38, 141.86, 139.21, 133.89, 133.15, 130.43, 129.91, 129.14, 128.90,
128.44, 128.37, 127.77, 126.96, 116.27, 116.00 (36ꢂAreC); 69.17, 63.96,
4.1.18. Macrocyclic lipopeptide amine p-tosylate (30g). White solid
(Yield 92.9%), Mp: 188e190 ꢀC. 1H NMR (CD3OD, 500 MHz)
d
: 7.96
(d, 2H, J¼8.35 Hz), 7.78 (d, 2H, J¼8.35 Hz), 7.70 (m, 8H), 7.60 (d, 2H,