Stereoselective preparation of 10α- and 10β-aryl derivatives of dihydroartemisinin

European Journal of Organic Chemistry

Volumn , Issue 11, 2003, Pages 2098-2114

  Haynes, Richard K ^a   Chan, Ho Wai ^a   Cheung, Man Ki ^a   Chung, Shuk Ting ^a   Lam, Wai Lun ^a   Tsang, Hing Wo ^a   Voerste, Arnd ^a,b   Williams, Ian D ^a  

^a HONG KONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Hong Kong)

^b BAYER AG   (Germany)

Author keywords

C Arylation; Diastereoselectivity; Dihydroartemisinin; Glycosylation; Grignard reaction

Indexed keywords

ARTEMISININ; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE;

ANTIMALARIAL ACTIVITY; ARTICLE; CATALYSIS; DERIVATIZATION; DRUG HALF LIFE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

EID: 0037596753     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200300064     Document Type: Article

References (134)

1. [19]). Artemether 3 (axial methoxyl) is sometimes referred to as β-artemether, to distinguish this compound from the "α"-epimer with an equatorial methoxyl group, in the malaria literature. This "convention," however, which has grown from the "normal" manner of representing structures of artemisinin and its derivatives in the voluminous literature of artemisinin derivatives (see refs. [2-7]), is the reverse of that normally used for designating the stereochemistry of sugars and their glycosides, in which, for example, α-D-glucopyranose possesses an axial hydroxy group. This inconsistency is unfortunate, but for convenience, here we continue to use the artemisinin stereochemical "convention."
2. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
3. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
4. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
5. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
6. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
7. For information on aspects of discovery and developmental work in China, see: X. Lusha, China Reconstructs. 1979, 48-49, and the various papers published by the Qinghaosu Research Groups on Qinghaosu, including, inter alia, Kexue Tongbao 1977, 22, 142; Chin. Med. Journal 1979, 92, 811-816; Scientia Sinica 1980, 23, 380-396; J. Tradit. Chin. Med. 1982, 2, 25-30; J. Tradit. Chin. Med. 1982, 2, 45-50.
8. China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials, J. Tradit. Chin. Med. 1982, 2, 9-16.
9. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
10. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
11. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
12. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
13. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
14. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
15. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
16. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
17. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
18. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
19. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
20. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
21. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
22. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
23. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
24. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
25. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
26. For reviews on clinical use, chemistry, pharmacology, and mode of action, see: L. J. Bruce-Chwatt, Brit. Med. J. 1982, 284, 767-768; D. L. Klayman, A. J. Lin, C.-C. Shen, L.-G. Zhuang, Med. Res. Rev. 1984, 4, 47-86; D. L. Klayman, Science 1985, 228, 1049-1055; X.-D. Luo, C.-C. Shen, Med. Res. Rev. 1987, 7, 29-52; P. I. Trigg, Economic and Medicinal Plant Research 1989, 3, 20-55; S. S. Zaman, R. P. Sharma, Heterocycles 1991, 32, 1593-1638; A. R. Butler, Y.-L. Wu Chem. Soc., Rev. 1992, 85-90; K. Arnold, Journal of the Hong Kong Medical Association 1993, 45, 189-196; T. T. Hien, N. J. White, Lancet 1993, 341, 603-608; Y.-L. Wu, Y. Li, Med. Chem. Res. 1995, 5, 569-586; S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery, W. Peters, Parasitology Today 1996, 12, 79-82; H. Ziffer, R. J. Highet, D. L. Klayman, Progress in the Chemistry of Organic Natural Products 1997, 72, 121-214; "The Use of Artemisinin and Its Derivatives as Anti-Malarial Drugs," Report of a Joint CTD/DMP/TDR Informal Consultation, Geneva 10-12 June 1998; Malaria Unit, Division of Control of Tropical Diseases, World Health Organization, Geneva; Y. Li, Y.-L. Wu, Médecine Tropicale 1998, 58, Supplement 3, 9-12; F. Nosten, T. T. Hien, N. J. White, Med Trop (Mars) 1998, 58, 45-49; G. H. Posner, Exp. Opin. Ther. Patents 1998, 8, 1487-1493; J. A. Vroman, M. Alvim-Gaston, M. A. Avery, Current Pharmaceutical Design 1999, 5, 101-138; M. A. van Agtmael, T. A. Eggelte, C. J. van Boxtel, Trends in Pharmacological Sciences 1999, 20, 199-205; N. J. White Philos. Trans. R. Soc., London, Ser. B 1999, 354, 739-749; World Health Organization (2000); Severe Falciparum Malaria, Trans. Roy. Soc., Trop. Med. Hygiene 2000, 94, Supplement 1, 36-37; P. Olliaro, R. K. Haynes, B. Meunier, Y. Yuthavong, Trends in Parasitology 2001, 17, 122-126.
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51. M. Merali, S. R. Meshnick, Antimicrob Agents Chemotherapy 1991, 35, 1225; K. Ou-Yang, E. C. Krug, J. J. Marr, R. L. Berens, Antimicrob Agents Chemotherapy 1990, 34, 1961; H. R. Chang, C. W. Jefford, J. C. Pechere, Antimicrob Agents Chemotherapy 1990, 34, 1961; D. M. Yang, F. Y. Liew, Parasitology 1993, 106, 7; X. Shuhua, B. Catto, Antimicrob Agents Chemotherapy 1989, 33, 1557, and references therein; S. Xiao, Z. Shi, S. Zhuo, C. Wang, Z. Zhang, B. Chu, J. Zhen, M. Chen, Chin. Med. J. 1996, 109, 272; M. E. Sarciron, C. Saccharin, A. F. Petavy, F. Peyron, Am. J. Trop. Med. Hyg. 2000, 62, 73-76; J. Utzinger, E. K. N'Goran, A. N'Dri, C. Lengeler, X. Shuhua, M. Tanner, Lancet 2000, 355, 1320-1325; X. Shuhua, Y. Jiqing, M. Jinying, G. Huifang, J. Peiying, M. Tanner, Parasitol. Int. 2000, 49, 25-30; S. H. Xiao, M. Booth, M. Tanner, Parasitol. Today 2000, 16, 122-126.
52. M. Merali, S. R. Meshnick, Antimicrob Agents Chemotherapy 1991, 35, 1225; K. Ou-Yang, E. C. Krug, J. J. Marr, R. L. Berens, Antimicrob Agents Chemotherapy 1990, 34, 1961; H. R. Chang, C. W. Jefford, J. C. Pechere, Antimicrob Agents Chemotherapy 1990, 34, 1961; D. M. Yang, F. Y. Liew, Parasitology 1993, 106, 7; X. Shuhua, B. Catto, Antimicrob Agents Chemotherapy 1989, 33, 1557, and references therein; S. Xiao, Z. Shi, S. Zhuo, C. Wang, Z. Zhang, B. Chu, J. Zhen, M. Chen, Chin. Med. J. 1996, 109, 272; M. E. Sarciron, C. Saccharin, A. F. Petavy, F. Peyron, Am. J. Trop. Med. Hyg. 2000, 62, 73-76; J. Utzinger, E. K. N'Goran, A. N'Dri, C. Lengeler, X. Shuhua, M. Tanner, Lancet 2000, 355, 1320-1325; X. Shuhua, Y. Jiqing, M. Jinying, G. Huifang, J. Peiying, M. Tanner, Parasitol. Int. 2000, 49, 25-30; S. H. Xiao, M. Booth, M. Tanner, Parasitol. Today 2000, 16, 122-126.
53. M. Merali, S. R. Meshnick, Antimicrob Agents Chemotherapy 1991, 35, 1225; K. Ou-Yang, E. C. Krug, J. J. Marr, R. L. Berens, Antimicrob Agents Chemotherapy 1990, 34, 1961; H. R. Chang, C. W. Jefford, J. C. Pechere, Antimicrob Agents Chemotherapy 1990, 34, 1961; D. M. Yang, F. Y. Liew, Parasitology 1993, 106, 7; X. Shuhua, B. Catto, Antimicrob Agents Chemotherapy 1989, 33, 1557, and references therein; S. Xiao, Z. Shi, S. Zhuo, C. Wang, Z. Zhang, B. Chu, J. Zhen, M. Chen, Chin. Med. J. 1996, 109, 272; M. E. Sarciron, C. Saccharin, A. F. Petavy, F. Peyron, Am. J. Trop. Med. Hyg. 2000, 62, 73-76; J. Utzinger, E. K. N'Goran, A. N'Dri, C. Lengeler, X. Shuhua, M. Tanner, Lancet 2000, 355, 1320-1325; X. Shuhua, Y. Jiqing, M. Jinying, G. Huifang, J. Peiying, M. Tanner, Parasitol. Int. 2000, 49, 25-30; S. H. Xiao, M. Booth, M. Tanner, Parasitol. Today 2000, 16, 122-126.
54. M. Merali, S. R. Meshnick, Antimicrob Agents Chemotherapy 1991, 35, 1225; K. Ou-Yang, E. C. Krug, J. J. Marr, R. L. Berens, Antimicrob Agents Chemotherapy 1990, 34, 1961; H. R. Chang, C. W. Jefford, J. C. Pechere, Antimicrob Agents Chemotherapy 1990, 34, 1961; D. M. Yang, F. Y. Liew, Parasitology 1993, 106, 7; X. Shuhua, B. Catto, Antimicrob Agents Chemotherapy 1989, 33, 1557, and references therein; S. Xiao, Z. Shi, S. Zhuo, C. Wang, Z. Zhang, B. Chu, J. Zhen, M. Chen, Chin. Med. J. 1996, 109, 272; M. E. Sarciron, C. Saccharin, A. F. Petavy, F. Peyron, Am. J. Trop. Med. Hyg. 2000, 62, 73-76; J. Utzinger, E. K. N'Goran, A. N'Dri, C. Lengeler, X. Shuhua, M. Tanner, Lancet 2000, 355, 1320-1325; X. Shuhua, Y. Jiqing, M. Jinying, G. Huifang, J. Peiying, M. Tanner, Parasitol. Int. 2000, 49, 25-30; S. H. Xiao, M. Booth, M. Tanner, Parasitol. Today 2000, 16, 122-126.
55. M. Merali, S. R. Meshnick, Antimicrob Agents Chemotherapy 1991, 35, 1225; K. Ou-Yang, E. C. Krug, J. J. Marr, R. L. Berens, Antimicrob Agents Chemotherapy 1990, 34, 1961; H. R. Chang, C. W. Jefford, J. C. Pechere, Antimicrob Agents Chemotherapy 1990, 34, 1961; D. M. Yang, F. Y. Liew, Parasitology 1993, 106, 7; X. Shuhua, B. Catto, Antimicrob Agents Chemotherapy 1989, 33, 1557, and references therein; S. Xiao, Z. Shi, S. Zhuo, C. Wang, Z. Zhang, B. Chu, J. Zhen, M. Chen, Chin. Med. J. 1996, 109, 272; M. E. Sarciron, C. Saccharin, A. F. Petavy, F. Peyron, Am. J. Trop. Med. Hyg. 2000, 62, 73-76; J. Utzinger, E. K. N'Goran, A. N'Dri, C. Lengeler, X. Shuhua, M. Tanner, Lancet 2000, 355, 1320-1325; X. Shuhua, Y. Jiqing, M. Jinying, G. Huifang, J. Peiying, M. Tanner, Parasitol. Int. 2000, 49, 25-30; S. H. Xiao, M. Booth, M. Tanner, Parasitol. Today 2000, 16, 122-126.
56. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
57. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
58. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
59. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
60. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
61. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment qf Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
62. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
63. R. K. Haynes, W. L. Lam, A. Voerste, G. Schmuck, G. Greif, "C-11 Aza derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305592.2; Europe, July 14, 1998; Europe, July 14, 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ester Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305595.5; July 14, 1998; Europe, July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-9 Sulfur-, Nitrogen-, and Carbon-Linked Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305628.4; July 14, 1998; Europe, International (PCT) PCT/GB99/02272; July 1999; R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, "C-10 Ether Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305594.8; July 14, 1998; Europe, July 1999.
64. R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, G. Schmuck, "C-10 Halogen-, Amino- and Carbon-Substituted Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305596.3; July 14, 1998; Europe; International (PCT) PCT/GB99/02267; July 1999.
65. R. K. Haynes, W. L. Lam, H. W. Chan, M. K. Cheung, H. W. Tsang, G. Greif, G. Schmuck, "C-10 Halogen-, Amino- and Carbon-Substituted Derivatives of Artemisinin for Treatment of Malaria, Coccidiosis, and Neosporosis", 98305596.3; July 14, 1998; Europe; International (PCT) PCT/GB99/02267; July 1999.
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131. [49]. Data for β-DHA in Table 4 is taken from our own determination conducted by Prof. Kinga Suwinska at the Polish Academy of Science, Warsaw, Poland.
132. [49]. Data for β-DHA in Table 4 is taken from our own determination conducted by Prof. Kinga Suwinska at the Polish Academy of Science, Warsaw, Poland.
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