2314
C. Gauthier et al. / Bioorg. Med. Chem. Lett. 19 (2009) 2310–2314
H-29), 4.42 (1H, d, J = 7.6 Hz, H-1), 3.97 (1H, m, H-500), 3.96 (1H, dd, J = 3.3,
1.6 Hz, H-200), 3.90 (1H, dd, J = 9.4, 6.2 Hz, H-5000), 3.83 (1H, dd, J = 3.1, 1.8 Hz, H-
000), 3.80 (1H, m, H-60), 3.74 (1H, dd, J = 9.5, 3.3 Hz, H-300), 3.65 (1H, m, H-60),
(C-60), 57.8 (C-17), 57.6 (C-5), 52.2 (C-9), 50.6 (C-18), 48.6 (C-19), 43.7 (C-14),
42.1 (C-8), 40.5 (C-4), 40.5 (C-1), 39.8 (C-13), 38.4 (C-22), 38.2 (C-10), 35.8 (C-
7), 33.6 (C-16), 31.9 (C-21), 31.0 (C-15), 28.5 (C-23), 27.5 (C-2), 27.1 (C-12),
22.2 (C-11), 19.7 (C-30), 19.4 (C-6), 18.1 (C-600), 18.0 (C-6000), 17.1 (C-24), 17.0
(C-25), 16.8 (C-26), 15.3 (C-27); HR-ESI-MS m/z 933.5179 [M+Na]+ (calcd for
2
3.62 (1H, m, H-3000), 3.57 (1H, m, H-30), 3.53 (1H, m, H-40), 3.44 (1H, m, H-20),
3.40 (1H, m, H-4000), 3.38 (1H, m, H-400), 3.31 (1H, m, H-50), 3.14 (1H, dd, J = 11.6,
4.3 Hz, H-3), 2.41 (1H, td, J = 11, 5.9 Hz, H-19), 1.68 (3H, s, H-30), 1.26 (3H, d,
J = 6.2 Hz, H-6000), 1.20 (3H, d, J = 6.2 Hz, H-600), 1.06 (3H, s, H-26), 1.03 (3H, s, H-
23), 0.98 (3H, s, H-27), 0.87 (3H, s, H-25), 0.84 (3H, s, H-24), 0.82 (3H, s, H-28);
13C NMR (CD3OD, 100 MHz): d 152.0 (C-20), 110.2 (C-29), 105.5 (C-10), 103.1
(C-1000), 102.1 (C-100), 90.4 (C-3), 80.5 (C-40), 79.2 (C-20), 78.2 (C-30), 76.5 (C-50),
74.0 (C-400), 73.7 (C-4000), 72.5 (C-2000), 72.2 (C-3000), 72.1 (C-300), 72.1 (C-200), 70.8
(C-5000), 70.0 (C-500), 62.0 (C-60), 57.4 (C-5), 51.9 (C-9), 49.6 (C-18), 49.4 (C-19),
44.1 (C-17), 44.0 (C-14), 42.1 (C-8), 41.1 (C-22), 40.4 (C-4), 40.3 (C-1), 39.5 (C-
13), 38.1 (C-10), 36.7 (C-16), 35.6 (C-7), 30.9 (C-21), 28.6 (C-15), 28.4 (C-23),
27.4 (C-2), 26.5 (C-12), 22.1 (C-11), 19.6 (C-30), 19.3 (C-6), 18.4 (C-28), 18.0 (C-
600), 17.9 (C-6000), 17.0 (C-24), 16.9 (C-25), 16.6 (C-26), 15.0 (C-27); HR-ESI-MS
m/z 903.5432 [M+Na]+ (calcd for C48H80O14Na: 903.5440). Compound 7:
C48H78O16Na: 933.5182). Compound 9: ½a D25
ꢂ
ꢀ 24:0 (c 0.2, MeOH); 1H NMR
(CD3OD, 400 MHz): d 5.37 (1H, d, J = 1.4 Hz, H-100), 4.84 (1H, d, J = 1.5 Hz, H-
1
000), 4.43 (1H, d, J = 7.7 Hz, H-10), 3.97 (1H, m, H-500), 3.97 (1H, dd, J = 3.2,
1.9 Hz, H-200), 3.91 (1H, dd, J = 9.5, 6.2 Hz, H-5000), 3.84 (1H, dd, J = 3.1, 1.8 Hz, H-
000), 3.80 (1H, m, H-60), 3.79 (1H, m, H-28), 3.75 (1H, dd, J = 9.6, 3.4 Hz, H-3000),
2
3.66 (1H, dd, J = 11.8, 3.7 Hz, H-60), 3.62 (1H, dd, J = 9.4, 3.2 Hz, H-300), 3.57 (1H,
m, H-30), 3.55 (1H, s, H-19), 3.54 (1H, m, H-40), 3.47 (1H, m, H-28), 3.44 (1H, m,
H-20), 3.41 (1H, m, H-4000), 3.38 (1H, m, H-400), 3.31 (1H, m, H-50), 3.16 (1H, dd,
J = 11.7, 4.2 Hz, H-3), 1.27 (3H, d, J = 6.2 Hz, H-6000), 1.21 (3H, d, J = 6.2 Hz, H-600),
1.03 (3H, s, H-23), 1.02 (3H, s, H-26), 0.96 (3H, s, H-27), 0.92 (3H, s, H-29), 0.89
(3H, s, H-25), 0.84 (3H, s, H-24), 0.83 (3H, s, H-30); 13C NMR (CD3OD,
100 MHz): d 105.5 (C-10), 103.1 (C-1000), 102.0 (C-100), 90.4 (C-3), 89.6 (C-19),
80.4 (C-40), 79.2 (C-20), 78.2 (C-30), 76.5 (C-50), 74.0 (C-400), 73.7 (C-4000), 72.5 (C-
½
a 2D5
ꢂ
þ 61:4 (c 0.1, MeOH); 1H NMR (CD3OD, 400 MHz):
d 5.36 (1H, d,
J = 1.3 Hz, H-100), 4.84 (1H, d, J = 1.5 Hz, H-1000), 4.68 (1H, br s, H-29), 4.57
(1H, br s, H-29), 4.42 (1H, d, J = 7.8 Hz, H-10), 3.97 (1H, m, H-500), 3.96 (1H, dd,
J = 3.2, 1.6 Hz, H-200), 3.91 (1H, dd, J = 9.5, 6.3 Hz, H-5000), 3.83 (1H, dd, J = 3.2,
1.8 Hz, H-2000), 3.79 (1H, m, H-60), 3.74 (1H, m, H-300), 3.73 (1H, m, H-28), 3.65
(1H, m, H-60), 3.62 (1H, m, H-3000), 3.58 (1H, m, H-30), 3.53 (1H, m, H-40), 3.44
(1H, m, H-20), 3.40 (1H, m, H-4000), 3.38 (1H, m, H-400), 3.30 (1H, m, H-50), 3.27
(1H, m, H-28), 3.13 (1H, dd, J = 11.4, 4.1 Hz, H-3), 2.41 (1H, td, J = 10.9, 5.9 Hz,
H-19), 1.68 (3H, s, H-30), 1.26 (3H, d, J = 6.2 Hz, H-6000), 1.20 (3H, d, J = 6.2 Hz,
H-600), 1.06 (3H, s, H-26), 1.03 (3H, s, H-23), 1.00 (3H, s, H-27), 0.86 (3H, s, H-
25), 0.84 (3H, s, H-24), 0.73 (1H, d, J = 9.2 Hz, H-5); 13C NMR (CD3OD,
100 MHz): d 151.9 (C-20), 110.3 (C-29), 105.5 (C-10), 103.1 (C-1000), 102.1 (C-
100), 90.4 (C-3), 80.4 (C-40), 79.2 (C-20), 78.2 (C-30), 76.5 (C-50), 74.0 (C-400), 73.7
(C-4000), 72.5 (C-2000), 72.2 (C-3000), 72.1 (C-300), 72.1 (C-200), 70.8 (C-5000), 70.0 (C-
500), 62.0 (C-60), 60.4 (C-28), 57.4 (C-5), 51.9 (C-9), 50.1 (C-18), 49.4 (C-19), 49.0
(C-17), 43.8 (C-14), 42.2 (C-8), 40.4 (C-4), 40.3 (C-1), 38.7 (C-13), 38.0 (C-10),
35.5 (C-22), 35.1 (C-7), 30.9 (C-21), 30.4 (C-16), 28.4 (C-23), 28.2 (C-15), 27.4
(C-2), 26.7 (C-12), 22.0 (C-11), 19.4 (C-30), 19.3 (C-6), 18.0 (C-600), 17.9 (C-6000),
17.0 (C-24), 16.9 (C-25), 16.6 (C-26), 15.2 (C-27); HR-ESI-MS m/z 919.5394
2
000), 72.2 (C-28), 72.2 (C-3000), 72.1 (C-300), 72.0 (C-200), 70.8 (C-5000), 70.0 (C-500),
62.0 (C-60), 57.6 (C-5), 52.5 (C-9), 48.1 (C-18), 42.7 (C-17), 41.9 (C-14), 41.9 (C-
8), 40.5 (C-1), 40.4 (C-4), 38.2 (C-10), 37.6 (C-16), 37.2 (C-20), 35.7 (C-13), 35.1
(C-7), 33.8 (C-21), 29.3 (C-29), 28.4 (C-23), 27.6 (C-15), 27.6 (C-22), 27.4 (C-2),
27.2 (C-12), 24.9 (C-30), 22.3 (C-11), 19.3 (C-6), 18.0 (C-600), 17.9 (C-6000), 17.3
(C-25), 17.0 (C-24), 16.3 (C-26), 14.0 (C-27); HR-ESI-MS m/z 919.5380 [M+Na]+
(calcd for C48H80O15Na: 919.5389). Compound 10: ½a D25
ꢀ 21:5 (c 0.2, MeOH);
ꢂ
1H NMR (CD3OD, 400 MHz): d 5.36 (1H, d, J = 1.2 Hz, H-100), 4.84 (1H, d,
J = 1.2 Hz, H-1000), 4.42 (1H, d, J = 7.7 Hz, H-10), 4.02 (1H, s, H-19), 3.97 (1H, dd,
J = 9.5, 6.2 Hz, H-500), 3.96 (1H, dd, J = 3.7, 1.5 Hz, H-200), 3.91 (1H, dd, J = 9.5,
6.3 Hz, H-5000), 3.83 (1H, dd, J = 3.7, 1.5 Hz, H-2000), 3.80 (1H, dd, J = 12.1, 1.6 Hz,
H-60), 3.74 (1H, dd, J = 9.5, 3.4 Hz, H-3000), 3.66 (1H, dd, J = 12.1, 4.1 Hz, H-60),
3.62 (1H, dd, J = 9.5, 3.4 Hz, H-300), 3.57 (1H, m, H-30), 3.53 (1H, m, H-40), 3.44
(1H, t, J = 8.1 Hz, H-20), 3.41 (1H, t, J = 9.6 Hz, H-4000), 3.38 (1H, t, J = 9.6 Hz, H-
400), 3.31 (1H, m, H-50), 3.15 (1H, dd, J = 11.4, 4.1 Hz, H-3), 2.19 (1H, t, J = 7.4 Hz,
H-13), 1.26 (3H, d, J = 6.2 Hz, H-6000), 1.20 (3H, d, J = 6.2 Hz, H-600), 1.03 (3H, s,
H-23), 1.00 (3H, s, H-30), 0.98 (3H, s, H-29), 0.93 (3H, s, H-26), 0.92 (3H, s, H-
27), 0.88 (3H, s, H-25), 0.84 (3H, s, H-24); 13C NMR (CD3OD, 100 MHz): d 182.3
(C-28), 105.5 (C-10), 103.1 (C-1000), 102.0 (C-100), 90.3 (C-3), 87.9 (C-19), 80.5 (C-
40), 79.3 (C-20), 78.2 (C-30), 76.5 (C-50), 74.0 (C-400), 73.7 (C-4000), 72.5 (C-2000),
72.2 (C-3000), 72.2 (C-300), 72.1 (C-200), 70.8 (C-5000), 70.1 (C-500), 62.0 (C-60), 57.6
(C-5), 52.7 (C-9), 47.9 (C-18), 47.6 (C-17), 41.8 (C-14), 41.1 (C-8), 40.5 (C-1),
40.4 (C-4), 38.2 (C-10), 37.7 (C-13), 35.0 (C-7), 34.6 (C-20), 33.6 (C-21), 32.8 (C-
16), 29.2 (C-30), 29.1 (C-15), 28.4 (C-23), 27.5 (C-22), 27.4 (C-2), 27.3 (C-12),
24.1 (C-29), 22.2 (C-11), 19.2 (C-6), 18.0 (C-600), 17.9 (C-6000), 17.3 (C-25), 17.0
(C-24), 16.0 (C-26), 14.1 (C-27); HR-ESI-MS m/z 933.5177 [M+Na]+ (calcd for
C48H78O16Na: 933.5182).
[M+Na]+ (calcd for C48H80O15Na: 919.5389). Compound 8: ½a D25
ꢀ 53:8 (c 0.1,
ꢂ
MeOH); 1H NMR (CD3OD, 400 MHz): d 5.36 (1H, d, J = 1.1 Hz, H-100), 4.84 (1H, d,
J = 1.2 Hz, H-1000), 4.70 (1H, m, H-29), 4.59 (1H, m, H-29), 4.42 (1H, d, J = 7.7 Hz,
H-10), 3.97 (1H, m, H-500), 3.96 (1H, dd, J = 3.2, 1.4 Hz, H-200), 3.90 (1H, dd,
J = 9.5, 6.2 Hz, H-5000), 3.83 (1H, dd, J = 3.0, 1.8 Hz, H-2000), 3.79 (1H, dd, J = 12.0,
1.4 Hz, H-60), 3.74 (1H, dd, J = 9.5, 3.4 Hz, H-300), 3.66 (1H, m, H-60), 3.62 (1H, m,
H-3000), 3.58 (1H, m, H-30), 3.53 (1H, m, H-40), 3.44 (1H, m, H-20), 3.41 (1H, m, H-
4
000), 3.38 (1H, m, H-400), 3.30 (1H, m, H-50), 3.13 (1H, dd, J = 11.6, 4.0 Hz, H-3),
3.03 (1H, td, J = 10.3, 4.1 Hz, H-19), 2.32 (1H, td, J = 12.6, 3.1 Hz, H-13), 1.69
(3H, s, H-30), 1.26 (3H, d, J = 6.2 Hz, H-6000), 1.20 (3H, d, J = 6.2 Hz, H-600), 1.02
(3H, s, H-23), 0.99 (3H, s, H-27), 0.96 (3H, s, H-26), 0.86 (3H, s, H-25), 0.83 (3H,
s, H-24), 0.73 (1H, d, J = 9.6 Hz, H-5); 13C NMR (CD3OD, 100 MHz): d 180.6 (C-
28), 152.3 (C-20), 110.3 (C-29), 105.6 (C-10), 103.2 (C-1000), 102.1 (C-100), 90.6
(C-3), 80.6 (C-40), 79.3 (C-20), 78.3 (C-30), 76.6 (C-50), 74.1 (C-400), 73.8 (C-4000),
72.6 (C-2000), 72.3 (C-300), 72.3 (C-3000), 72.2 (C-200), 70.9 (C-5000), 70.1 (C-500), 62.1
34. O’Brien, J.; Wilson, I.; Orton, T.; Pognan, F. Eur. J. Biochem. 2000, 267, 5421.
35. Kessler, J. H.; Mullauer, F. B.; de Roo, G. M.; Medema, J. P. Cancer Lett. 2007, 25,
132.
36. Wang, Y.; Zhang, Y.; Zhu, Z.; Zhu, S.; Li, Y.; Li, M.; Yu, B. Bioorg. Med. Chem. 2007,
15, 2528.