W.-M. Wu et al. / Bioorg. Med. Chem. Lett. 13 (2003) 1645–1647
1647
postulated primary and secondary carbon radicals were
confirmed not only by ESR spectra,4,5 but also by the
identification of both free radical adducts. On the other
side, with these standard samples in our hand we have
detected the products after incubation of artemether
with or without S. japonicium in different media. It was
found that RPMI 1640 contained a number of amino
acids including cysteine, therefore, artemether already
converted to its free radical reaction products and
cysteine adducts before it reached to the gut of parasite.
The observation and deduction of biological respect
were reported in detail elsewhere.3
F.; Mareda, J.; Millasson-Schmidt, P.; Brunner, G.; Burger,
U. Helv. Chim. Acta 1996, 79, 1475.
8. Wu, Y.; Yue, Z.-Y.; Wu, Y.-L. Angew. Chem., Int. Ed.
1999, 38, 2580.
9. Wang, D.-Y.; Wu, Y.-L. Chem. Commun. 2000, 2193.
10. Wang, D.-Y.; Wu, Y.-L.; Wu, Y.-K.; Liang, J.; Li, Y. J.
Chem. Soc., Perkin Trans. 1 2001, 605.
11. Robert, A.; Dechy-Cabaret, O.; Cazelles, J.; Meunier, B.
Acc. Chem. Res. 2002, 35, 167.
12. Compound 5: Mp: 66–68 ꢁC. ½aD20=+86 (c 0.59, CHCl3),
IR (KBr) n: 3552, 2989, 1758, 1466, 1240, 1094 cmꢀ1 1H
.
NMR (300 MHz, CDCl3) d: 0.89 (3H, d, J=7.3Hz), 0.94 (3H,
d, J=6.5 Hz), 0.97 (3H, t, J=5.9 Hz), 2.12 (3H, s), 2.48 (1H,
m), 3.43 (3H, s), 4.59 (1H, d, J=4.0 Hz), 6.29 (1H, s). EI–MS
(m/z): 281, 267, 209, 163. Anal. calcd for C16H28O5: C, 63.97;
H, 9.40. Found: C, 63.94; H, 9.42.
Acknowledgements
13. Compound 6: Syrup, ½a2D5=ꢀ24.2 (c 0.5, CH3CN/
H2O=1:1). IR (KBr) n: 3420, 2930, 1634, 1386. 1H NMR
(400 MHz, D2O) d: 0.96 (3H, d, J=6.2 Hz, 13-H3), 1.00 (3H, d,
J=7.2 Hz, 14-H3), 1.77 (3H, s, 15-H3), 1.95 (2H, m), 2.20 (1H,
m), 2.35 (1H, m), 2.97 (1H, dd, J=5.6 Hz, 11.3 Hz, 3-H), 3.19
(1H, dd, J=7.0 Hz, 14.5 Hz, 30-H), 3.25 (1H, dd, J=4.6 Hz,
14.6 Hz, 30-H), 3.99 (1H, dd, J=4.4 Hz, 7.0 Hz, 20-H), 4.93(1H,
d, J=8.6 Hz, 12-H), 5.59 (1H, s, 5-H). 13C NMR (75 MHz,
This work was supported by the National Natural
Science Foundation of China, the Chinese Academy of
Sciences, and the State Ministry of Science and
Technology.
D2O–CD3COCD3) d: 13.73 (CH3), 18.72 (CH3), 22.83(CH ),
3
References and Notes
22.90 (CH2), 30.93 (CH2), 32.68 (CH2), 33.35 (CH), 34.22
(CH2), 35.12 (CH), 41.89 (CH), 47.72 (CH), 49.68 (CH), 54.86
CH), 83.93 (C), 95.92 (CH), 97.19 (CH), 111.18 (C), 172.81
(CO). ESI-MS (m/z): 388 (M+1), 775 (2M+1). ESI-HRMS
calcd for C18H30NO6S: 388.1788. Found: 388.1771.
1. Li, Y.; Yu, P.-L.; Chen, Y.-X.; Li, L.-Q.; Gai, Y.-Z.; Wang,
D.-S.; Zheng, Y.-P. Kexue Tongbao 1979, 24, 667. Li, Y.; Yu,
P.-L.; Chen, Y.-X.; Li, L.-Q.; Gai, Y.-Z.; Wang, D.-S.; Zheng,
Y.-P. Yaoxue Xuebao 1981, 16, 429.
2. Xiao, S.-H.; Booth, M.; Tanner, M. Parasit. Today 2000,
16, 122.
3. Xiao, S.-H.; Wu, Y.-L.; Tanner, M.; Wu, W.-M.; Utzinger,
J.; Mei, J.-Y.; Scorneaux, B.; Chollet, J.; Zhai, Z., Parasit.
Res. 2003, 89, 459.
4. Wu, W.-M.; Wu, Y.-K.; Wu, Y.-L.; Yao, Z.-J.; Zhou, C.-
M.; Li, Y.; Shan, F. J. Am. Chem. Soc. 1998, 120, 3316, and
cited references therein.
5. Butler, A. R.; Girbert, B. C.; Hulme, P.; Irvine, L. R. Free
Rad. Res. 1998, 28, 471.
6. Cumming, J. N.; Ploypradith, P.; Posner, G. H. In
Advances in Pharmacology; Academic: 1997; Vol. 37, p 253.
7. Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger,
14. Compound 7: Syrup, ½a2D5=+27.6 (c 1.0, CH3CN/
H2O=1:1), ½ꢀ25=+33.9 (c 0.8, H2O). IR (KBr) n: 3408, 2878,
D
1762, 1633, 1224 cmꢀ1. 1H NMR (400 MHz, D2O) d: 0.96 (3H,
d, J=7.3Hz, 14-H 3), 0.99 (3H, d, J=6.4 Hz, 13-H3), 2.26 (3H,
s, CH3CO), 2.38 (1H, m), 2.59 (2H, m), 2.84 (1H, m), 3.13
(1H, dd, J=7.1 Hz, 14.8 Hz, 30-H), 3.20 (1H, dd, J=4.4 Hz,
14.8 Hz, 30-H), 3.46 (3H, s, OCH3), 3.96 (1H, dd, J=4.4 Hz,
7.2 Hz, 20-H), 4.78 (1H, d, J=4.0 Hz, 12-H), 6.33 (1H, s, 5-H).
13C NMR (100 MHz, D2O–CD3COCD3) d: 11.96 (CH3), 20.28
(CH3), 20.77 (CH3), 24.34 (CH2), 27.92 (CH2), 31.28, 32.01
(CH2), 33.24 (CH2), 35.14 (CH2), 35.14, 47.57, 53.51, 53.62,
55.46, 73.20 (C), 87.02, 103.76, 171.77 (CO), 172.35 (CO). ESI-
MS (m/z): 420 (M+1), 839 (2M+1). ESI-HRMS calcd for
C19H34NO7S: 420.2050. Found: 420.2039.