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Y. Takeda et al. / Bioorg. Med. Chem. Lett. 13 (2003) 185–190
C, 64.40; H, 7.30; N, 3.00; Found: C, 64.40; H, 7.32; N, 2.86;
IR (KBr): 3430, 2969, 1716, 1602, 1492, 1452, 1367 cmꢁ1; [a]D24
ꢁ13.3ꢀ (c 0.2, CHCl3).
1592, 1490, 1452 cmꢁ1; [a]D25 ꢁ8.7ꢀ (c 0.48, CHCl3). 20b: mp:
160–165 ꢀC; H NMR (CDCl3) d: 1.30 (3H, s), 1.40–2.05 (5H,
1
m), 1.48 (3H, s), 1.51 (3H, s), 1.59 (3H, s), 1.61 (3H, s), 2.13–
2.22 (2H, m), 2.52 (3H, s), 2.53–2.70 (4H, m), 2.71 (1H, dd,
J=5.1, 13.2 Hz), 2.77 (1H, dd, J=3.9, 13.2 Hz), 2.93 (1H, d,
J=5.4 Hz), 3.73 (4H, t, J=4.4 Hz), 4.08 (1H, d, J=7.3 Hz),
4.20 (1H, d, J=8.3 Hz), 4.35 (1H, d, J=8.3 Hz), 4.93 (1H, s),
5.00 (1H, t, J=4.4 Hz), 5.12 (1H, d, J=7.3 Hz), 5.69 (1H, d,
J=9.5 Hz), 5.96 (1H, d, J=5.4 Hz), 5.98 (1H, br s), 6.21 (1H,
br t, J=8.8 Hz), 7.25–7.35 (1H, m), 7.42–7.55 (5H, m), 7.61
(1H, t, J=7.5 Hz), 7.72 (1H, dt, J=1.5, 7.5 Hz), 7.87 (2H, d,
J=7.8 Hz), 7.91 (1H, d, J=7.5 Hz), 8.15 (2H, d, J=7.5 Hz),
8.52 (1H, d, J=4.4 Hz); FAB-MS (m/z): 924 (M+H)+. Anal.
calcd for C51H61N3O13ꢂ 1.25H2O: C, 64.71; H, 6.76; N, 4.44;
Found: C, 64.71; H, 6.78; N, 4.37; IR (KBr): 3421, 2950, 1720,
1664, 1592, 1511, 1482, 1436 cmꢁ1; [a]D25 ꢁ10.4ꢀ (c 0.42,
CHCl3).
11. Spectral data of 15 are as follows: mp: 160–162 ꢀC; 1H
NMR (CDCl3) d: 1.27 (3H, s), 1.30–2.15 (6H, m), 1.43 (9H, s),
1.48 (3H, s), 1.60 (3H, s), 1.73 (3H, s), 2.27–2.38 (1H, m), 2.37
(3H, s), 2.55–2.68 (4H, m), 2.72 (1H, dd, J=5.1, 13.6 Hz), 2.79
(1H, dd, J=3.9, 13.6 Hz), 2.93 (1H, d, J=4.9 Hz), 3.74 (4H, t,
J=4.6 Hz), 4.12 (1H, d, J=7.1 Hz), 4.22 (1H, d, J=8.3 Hz),
4.33 (1H, d, J=8.3 Hz), 4.85 (1H, br s), 4.88–4.95 (2H, m),
5.14 (1H, t, J=4.4 Hz), 5.23 (1H, d, J=7.1 Hz), 5.35 (1H, br
d, J=9.4 Hz), 5.97 (1H, br d, J=9.4 Hz), 5.98 (1H, d, J=4.9
Hz), 6.09 (1H, br t, J=8.3 Hz), 7.23 (1H, dd, J=5.2, 7.1 Hz),
7.42 (1H, d, J=7.8 Hz), 7.47 (2H, t, J=7.8 Hz), 7.60 (1H, t,
J=7.8 Hz), 7.72 (1H, dt, J=1.5, 7.8 Hz), 8.12 (2H, d, J=7.8
Hz), 8.53 (1H, br d, J=5.2 Hz); FAB-MS (m/z): 906
(M+H)+. Anal. calcd for C48H63N3O14: C, 63.63; H, 7.01; N,
4.64; Found: C, 63.62; H, 7.03; N, 4.47; IR (KBr): 2950, 1722,
1689, 1592, 502, 1434, 1365 cmꢁ1; [a]D23 ꢁ5.6ꢀ (c 1.06, CHCl3).
12. Georg, G. I.; Harrima, G. C. B.; Hepperle, M.; Himes,
R. H. Bioorg. Med. Chem. Lett. 1994, 4, 1381.
15. A colorless, prismatic crystal of C52H79N3O18 having
approximate dimensions of 0.30ꢃ0.20ꢃ0.10 mm was grown
from MeOH–MeCN and mounted in a glass capillary. The
lattice parameters and intensities were measured on
a
13. Hart, D. J.; Kanai, K.; Thomas, D. G.; Yang, T.-K. J.
Org. Chem. 1983, 48, 289.
14. Spectral data of 20a and 20b are as follows; 20a: mp: 150–
RIGAKU AFC7R diffractometer with monochromated CuKa
radiation by using the o-2y scan technique. The compound
crystallized in orthorhombic space group P212121 with cell
152 ꢀC; H NMR (CDCl3) d: 1.29 (3H, s), 1.42 (9H, s), 1.48
dimensions a=17.1295 A, b=30.1980 A, c=10.3530 A,
1
˚
˚
˚
3
˚
(3H, s), 1.53 (3H, s), 1.56 (3H, s), 1.59 (3H, s), 1.60–1.80 (1H,
m), 1.83–2.50 (5H, m), 2.51 (3H, s), 2.50–2.84 (6H, m), 2.92
(1H, d, J=5.4 Hz), 3.74 (4H, t, J=4.4 Hz), 4.11 (1H, d, J=6.8
Hz), 4.20 (1H, d, J=8.3 Hz), 4.34 (1H, d, J=8.3 Hz), 4.93
(1H, s), 5.01 (1H, t, J=4.4 Hz), 5.16 (1H, d, J=6.8 Hz), 5.95
(1H, d, J=5.4 Hz), 6.04 (1H, d, J=10.2 Hz), 6.16 (1H, br t,
J=8.8 Hz), 7.20–7.35 (1H, m), 7.40–7.60 (3H, m), 7.60 (1H, t,
J=7.3 Hz), 7.72 (1H, t, J=7.4 Hz), 8.15 (2H, d, J=7.3 Hz),
8.49 (1H, d, J=4.4 Hz); FAB-MS (m/z): 920 (M+H)+. Anal.
calcd for C49H65N3O14ꢂ 1.25H2O: C, 62.44; H, 7.22; N, 4.46;
Found: C, 62.48; H, 7.19; N, 4.45; IR (KBr): 3440, 2973, 1716,
V=5335.4 A . The structure was solved by the direct method
with the program SIR92. After several cycles of refinement,
eight extra peaks of electron density are observed. They were
assigned as four MeOH molecules. For Z=4 and
F.W.=1034.21, the calculated density was 1.28 g/cm3. The
final R value was 0.061.
16. PC-6/VCR29-9: PC-6 cell line, which is resistant to Vin-
cristine1. PC-6/VP1-1: PC-6 cell line, which is resistant to VP-
16 (Etoposide1).
17. Poste, G.; Doll, J.; Hart, I. R.; Fidler, I. J. Cancer Res.
1980, 40, 1636.