H. Zhu et al. / Bioorg. Med. Chem. Lett. 15 (2005) 4936–4943
4943
20. (a) Wang, L. H.; Gou, S. H.; Chen, Y. J.; Liu, Y. Bioorg.
Med. Chem. Lett. 2005, 15, 3417; (b) Kaplan, M. A.;
Granatek, A. P. Eur. Pat. 41,644 A2, 1981.
21. Haines, A. H.; Morley, C.; Murrer, B. A. J. Med. Chem.
1989, 32, 742.
22. Kim, D. K.; Kim, G.; Gam, J.; Cho, Y. B.; Kim, H. T.;
Tai, J. H.; Kim, K. H.; Hong, W. S.; Park, J. G. J. Med.
Chem. 1994, 37, 1471.
23. Odham, G.; Pettersson, B.; Stenhagen, E. Acta Chem.
Scand. B 1974, 28, 36.
3 with concentrated HCl aqueous solution which is
25
cooled to get white crystal. Data for VIIa. ½aꢂD ¼ þ11:37
(c = 1.0, H2O); IR (KBr) 3030 (NH3+), 2023, 1599, 1487
(NH3+), 1126, 1100, 1063 (C-O) cmꢀ1 1H NMR
.
(500 MHz, D2O): d 3.69 (m, 1H, 1H of CH3OCH),
3.35 (s, 3H, 3H of CH3OCH), 3.22–3.18 (m, 1H, 1H of
CH2NH3Cl), 3.08–3.05 (m, 2H, 2H of CH2NH3Cl), 2.99-
2.97 (m, 1H, 1H of CH2NH3Cl), 1.92–1.88 (m, 2H,
2H of CH2CH2NH3Cl). ESI-MS m/z [Mꢀ2Clꢀ-
H+]+ = 119(100%). Anal. Calcd for C5H16N2OCl2: C,
31.43; H, 8.44; N, 14.66. Found: C, 31.60; H, 8.34; N,
14.37. (R)-2-Methoxy-1,4-aminobutane was obtained in a
24. Carmack, M.; Kelley, C. J. J. Org. Chem. 1968, 33, 2171.
25. Rubin, L. J.; Lardy, H. A.; Fisher, H. O. L. J. Am. Chem.
Soc. 1952, 74, 425.
25
similar manner. ½aꢂD ¼ ꢀ11:32 (c = 1.0, H2O). The syn-
25
26. Synthesis of (S)-2-methoxy-1,4-ditosylbutane (IVa). To
6.52 g of IIIa in 80 ml of dry pyridine, and cooled to 0 °C,
20.2 g of finely powered p-toluenesulfonyl chloride was
added in one portion. The mixture was stirred at 0 °C for
1.5 h and then placed in refrigerator overnight. Two
hundred milliliters of water was added to the mixture in
ice-water bath and the reaction mixture was stirred for
another 0.5 h. After cooling in refrigerator for 3 days, the
white crystal was obtained from the mixture. After
filtration, the resulted white crystal was dried in vacuum.
Data for IVa. IR (KBr) 3065, 1596, 1494 (phenyl), 1459,
1360 (S@O), 1312, 1174 (S@O), 1136, 1095, 1076, 1038,
938, 852, 812, 754, 670 cmꢀ1. 1H NMR (500 MHz, CDCl3):
d 7.78–7.76 (m, 4H, 4H of ArH), 7.36–7.34 (m, 4H, 4H of
ArH), 4.14–4.11 (m, 1H, 1H of CH3C6H4SO3CH2), 4.07–
4.02 (m, 2H, 2H of 2CH3C6H4SO3CH2), 3.94–3.91 (m, 1H,
1H of CH3C6H4SO3CH2), 3.47–3.45 (m, 1H, 1H of
CH3OCH), 3.21 (s, 3H, 3H of CH3OCH), 2.45 (s,
6H, 6H of 2ArCH3), 1.81–1.78 (m, 1H, 1H of
CH3C6H4SO3 CH2CH2), 1.75–1.62 (m, 1H, 1H of
CH3C6H4SO3CH2CH2). Anal. Calcd for C19H24O7S2: C,
53.25; H, 5.64. Found: C, 53.15; H, 5.61.(R)-2-Methoxy-
1,4-ditosylbutane was prepared in a similar manner and
spectral data were identical with that of (S)-2-methoxy-1,4-
ditosylbutane. (S)-2-Ethoxy-1,4-ditosylbutane (IVb) was
synthesized in a similar procedure to that for IVa. Data for
IVb. IR (KBr) 3032, 1597, 1495 (phenyl), 1459, 1354
(S@O), 1308, 1176 (S@O), 1126, 1101, 1079, 1037, 936, 858,
820, 768, 672 cmꢀ1. 1H NMR (500 MHz, CDCl3): d 7.80–
7.78 (m, 4H, 4H of ArH), 7.38–7.36 (m, 4H, 4H of ArH),
4.16–4.15 (m, 1 H, 1 H of CH3C6H4SO3CH2), 4.09–4.07
(m, 1 H, 1 H of CH3C6H4SO3CH2), 4.02–3.99 (m, 1 H, 1 H
of CH3C6H4SO3CH2), 3.96–3.93 (m, 1 H, 1 H of
CH3C6H4SO3CH2), 3.52–3.49 (m, 2H, 2H of
CH3CH2OCH), 3.27–3.25 (m, 1H, 1H of CH3CH2OCH),
2.48 (s, 6H, 6H of 2ArCH3), 1.82–1.80 (m, 1H, 1H of
CH3C6H4SO3CH2CH2), 1.74–1.72 (m, 1H, 1H of
CH3C6H4SO3CH2CH2), 1.04–1.01 (m, 3H, 3H of
CH3CH2OCH). Anal. Calcd for C20H26O7S2: C, 54.28;
H, 5.92. Found: C, 54.30; H, 6.04. (R)-2-Ethoxy-1,4-
ditosylbutane was prepared in a similar manner and
spectral data were identical with that of (S)-2-ethoxy-1,4-
ditosylbutane.
thesis of (S)-2-ethoxy-1,4-aminobutane (VIIb) was anal-
ogous to that for VIIa. Data for VIIb. ½aꢂD ¼ þ10:88
(c = 1.0, H2O); IR (KBr) 3032 (NH3+), 2010, 1608, 1497
;
(NH3+), 1163, 1076, 1032 (C–O) cmꢀ1 1H NMR
(500 MHz, D2O): d = 3.74 (m, 1H, 1H of CH3CH2OCH),
3.55–3.52 (m, 2H, 2H of CH3CH2OCH), 3.15–3.13 (m,
1H, 1H of CH2NH3Cl), 3.04–3.00 (m, 2H, 2H of
CH2NH3Cl), 2.94–2.92 (m, 1H, 1H of CH2NH3Cl),
1.87–1.86 (m, 2H, 2H of CH2CH2NH3Cl), 1.11–1.07
(m, 3H, 3H of CH3CH2OCH). ESI-MS m/z [Mꢀ2Clꢀ-
H+]+ = 133 (100%). Anal. Calcd for C6H18N2OCl2: C,
35.13; H, 8.84; N, 13.66. Found: C, 35.40; H, 8.63; N,
13.70. (R)-2-Ethoxy-1,4-aminobutane was also synthe-
25
sized in a similar manner. ½aꢂD ¼ ꢀ10:82(c = 1.0, H2O)..
29. Dhara, S. C. Indian J. Chem. 1970, 8, 193.
30. Reedijk, J.; Fichtinger-Schepman, A. M. J.; Van Ooster-
on, A. T.; Van de Putte, P. Struct. Bonding 1987, 67, 53.
31. Lippard, S. J. Pure Appl. Chem. 1987, 59, 731.
32. General procedure (method 2) for the synthesis of
complexes 1a–d, 10a–d, 2a–b, 20a–b, 3c, and 30c. A
suspension of diiodoplatinum (II) complex (2.0 mmol)
and silver carboxylate (4.0 mmol) or disilver carboxylate
(2.0 mmol) in H2O (100 ml) was stirred at 60 °C in the
dark overnight. The resulting silver iodide was filtered
through a pad of Celite. The filtrate was concentrated
under a reduced pressure and white precipitate was
collected and dried in vacuum.
33. General procedure (method 1) for the synthesis of
complexes 3a–b, 30a–b, 4a–b, 40a–b, 5a–b, and 50a–b.
To a stirred suspension of diiodoplatinum (II) complex
(2.0 mmol) in H2O (30 ml) was added a solution of
AgNO3 (4.0 mmol) in H2O (20 ml). Under the nitrogen
atmosphere the mixture was heated at 40 °C for 24 h in
the dark and filtered though a pad of Celite. Then
disodium glycolate (2.0 mmol), sodium chloride
(4.0 mmol) or sodium glycolate (4.0 mmol) aqueous
solution was added to the above filtration. The resultant
solution was then mixed with the above filtration and
stirred at 40 °C for 24 h. The reaction mixture was
concentrated and ethanol was added before filtration.
The filtrate was concentrated to afford yellow syrup,
which gave a precipitate after addition of ether. The
resulting precipitate was then filtered quickly to give a
very hygroscopic solid.
27. Scheurer, A.; Mosset, P.; Saalfrank, R. W. Tetrahedron:
Asymmetry 1997, 8, 1243.
34. Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.;
Paull, K.; Vistica, D. J. Natl. Cancer Inst. 1991, 83, 757.
35. Mellish, K. J.; Kelland, L. R.; Harrap, K. R. Br. J. Cancer
1993, 68, 240.
36. Skehan, P.; Stroreng, R.; Scudiero, D.; Monks, A.;
McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.;
Kenney, S.; Boyd, M. R. J. Natl. Cancer Inst. 1990, 82,
1107.
28. Synthesis
of
(S)-2-Methoxy-1,4-aminobutane(VIIa).
Ditosylate IVa (7.49 g) and sodium azide (2.5 g) in
DMF (150 ml) were stirred at 100 °C for 8 h, cooled to
room temperature, and the mixture was poured into
200 ml water and extracted with ether. The organic phase
was dried over anhydrous sodium sulfate. After concen-
trated under reduced pressure, the afforded yellow syrup
was dissolved in ethanol and then directly hydrogenated
using Pd/C as catalyst under 72 atm of H2 pressure. The
reaction mixture was concentrated and adjusted to pH 2–
37. Yang, M.; Hu, Q. Y.; Zhang, L. R.; Zhu, S. M.; Zou,
J.; Li, R. C.; Wang, K. S. Afr. J. Chem. 1997, 50,
227.