From Qinghao, Marvelous Herb of Antiquity, to the Antimalarial Trioxane Qinghaosu - And Some Remarkable New Chemistry

Accounts of Chemical Research

Volumn 30, Issue 2, 1997, Pages 73-79

  Haynes, Richard K ^a,c,d,e   Vonwiller, Simone C ^b,f  

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

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF KARLSRUHE   (Germany)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

^e MONASH UNIVERSITY   (Australia)

^f LEIBNIZ UNIVERSITY HANNOVER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001815264     PISSN: 00014842     EISSN: None     Source Type: Journal    
DOI: 10.1021/ar950058w     Document Type: Article

References (103)

1. Xueqin, Xao Honglou Meng, translated as The Story of the Stone by David Hawkes: Penguin Classics: Harmondsworth, London, 1977; Vol. 2 (The Crab-Flower Club), Chapter 51.
2. Xueqin, Xao Honglou Meng, translated as The Story of the Stone by David Hawkes: Penguin Classics: Harmondsworth, London, 1977; Vol. 2 (The Crab-Flower Club), Chapter 51.
3. A description of uses of qinghao appears on pp 944-946 of the 1991 edition of Ben Cao Gang Mu; People's Health Publishing, Lanzhou Printing Press: Lanzhou, China, 1991.
4. For reviews with references to development and clinical use, see: Qinghaosu Antimalaria Coordinating Research Group. Antimalaria Studies on Qinghaosu. Chin. Med. J. 1979, 92, 811. Klayman, D. L. Science 1985, 228, 1049. Luo, X.-D.; Shen, C.-C. Med. Res. Rev. 1987, 7, 29. Trigg, P. I. Econ. Med. Plant Res. 1989, 3, 19. Woerdenbag, H. J.; Lugt. C. B.; Pras, N. Pharm. Weekbl., Sci. Ed. 1990, 12, 169.
5. For reviews with references to development and clinical use, see: Qinghaosu Antimalaria Coordinating Research Group. Antimalaria Studies on Qinghaosu. Chin. Med. J. 1979, 92, 811. Klayman, D. L. Science 1985, 228, 1049. Luo, X.-D.; Shen, C.-C. Med. Res. Rev. 1987, 7, 29. Trigg, P. I. Econ. Med. Plant Res. 1989, 3, 19. Woerdenbag, H. J.; Lugt. C. B.; Pras, N. Pharm. Weekbl., Sci. Ed. 1990, 12, 169.
6. For reviews with references to development and clinical use, see: Qinghaosu Antimalaria Coordinating Research Group. Antimalaria Studies on Qinghaosu. Chin. Med. J. 1979, 92, 811. Klayman, D. L. Science 1985, 228, 1049. Luo, X.-D.; Shen, C.-C. Med. Res. Rev. 1987, 7, 29. Trigg, P. I. Econ. Med. Plant Res. 1989, 3, 19. Woerdenbag, H. J.; Lugt. C. B.; Pras, N. Pharm. Weekbl., Sci. Ed. 1990, 12, 169.
7. For reviews with references to development and clinical use, see: Qinghaosu Antimalaria Coordinating Research Group. Antimalaria Studies on Qinghaosu. Chin. Med. J. 1979, 92, 811. Klayman, D. L. Science 1985, 228, 1049. Luo, X.-D.; Shen, C.-C. Med. Res. Rev. 1987, 7, 29. Trigg, P. I. Econ. Med. Plant Res. 1989, 3, 19. Woerdenbag, H. J.; Lugt. C. B.; Pras, N. Pharm. Weekbl., Sci. Ed. 1990, 12, 169.
8. For reviews with references to development and clinical use, see: Qinghaosu Antimalaria Coordinating Research Group. Antimalaria Studies on Qinghaosu. Chin. Med. J. 1979, 92, 811. Klayman, D. L. Science 1985, 228, 1049. Luo, X.-D.; Shen, C.-C. Med. Res. Rev. 1987, 7, 29. Trigg, P. I. Econ. Med. Plant Res. 1989, 3, 19. Woerdenbag, H. J.; Lugt. C. B.; Pras, N. Pharm. Weekbl., Sci. Ed. 1990, 12, 169.
9. For usage in treatment of severe malaria, see inter alia: Li, G-Q.; Guo, X.-B.; Jin, R,; Wang, Z.-C; Jian, H.-X.; Li, Z.-Y. J. Tradit. Chin. Med. 1982, 2, 125. Hien, T. T.; White, N. J. Lancet 1993, 341, 603. Arnold, K. J. Hong Kong Med. Assoc. 1993, 45, 189. White, N. J. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S5. Looareesuwan, S. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S9.
10. For usage in treatment of severe malaria, see inter alia: Li, G-Q.; Guo, X.-B.; Jin, R,; Wang, Z.-C; Jian, H.-X.; Li, Z.-Y. J. Tradit. Chin. Med. 1982, 2, 125. Hien, T. T.; White, N. J. Lancet 1993, 341, 603. Arnold, K. J. Hong Kong Med. Assoc. 1993, 45, 189. White, N. J. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S5. Looareesuwan, S. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S9.
11. For usage in treatment of severe malaria, see inter alia: Li, G-Q.; Guo, X.-B.; Jin, R,; Wang, Z.-C; Jian, H.-X.; Li, Z.-Y. J. Tradit. Chin. Med. 1982, 2, 125. Hien, T. T.; White, N. J. Lancet 1993, 341, 603. Arnold, K. J. Hong Kong Med. Assoc. 1993, 45, 189. White, N. J. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S5. Looareesuwan, S. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S9.
12. For usage in treatment of severe malaria, see inter alia: Li, G-Q.; Guo, X.-B.; Jin, R,; Wang, Z.-C; Jian, H.-X.; Li, Z.-Y. J. Tradit. Chin. Med. 1982, 2, 125. Hien, T. T.; White, N. J. Lancet 1993, 341, 603. Arnold, K. J. Hong Kong Med. Assoc. 1993, 45, 189. White, N. J. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S5. Looareesuwan, S. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S9.
13. For usage in treatment of severe malaria, see inter alia: Li, G-Q.; Guo, X.-B.; Jin, R,; Wang, Z.-C; Jian, H.-X.; Li, Z.-Y. J. Tradit. Chin. Med. 1982, 2, 125. Hien, T. T.; White, N. J. Lancet 1993, 341, 603. Arnold, K. J. Hong Kong Med. Assoc. 1993, 45, 189. White, N. J. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S5. Looareesuwan, S. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S9.
14. For details of comparative trials with artemether (2) and quinine in the treatment of severe falciparum malaria, see: van Hensbroek, M. B.; Onyiorah, E.; Jaffar, S.; Schneider, G.; Palmer, A.; Frenkel, J.; Enwere, G.; Forck, S.; Nusmeijer, A.; Bennet, S.; Greenwood, B.; Kwiatowski, N. N. Engl. J. Med. 1996, 335, 69. D. Hien, T. T.; Day, P. J. N.; Phu, N. H.; Hoang, N. T.; Chau, T. T. H.; Loc, P. P.; Sinh, D. X.; Cuong, L. V.; Vinh, H.; Waller, D.; Peto, T. E. A.; White, N. J. N. Engl. J. Med. 1996, 335, 76.
15. For details of comparative trials with artemether (2) and quinine in the treatment of severe falciparum malaria, see: van Hensbroek, M. B.; Onyiorah, E.; Jaffar, S.; Schneider, G.; Palmer, A.; Frenkel, J.; Enwere, G.; Forck, S.; Nusmeijer, A.; Bennet, S.; Greenwood, B.; Kwiatowski, N. N. Engl. J. Med. 1996, 335, 69. D. Hien, T. T.; Day, P. J. N.; Phu, N. H.; Hoang, N. T.; Chau, T. T. H.; Loc, P. P.; Sinh, D. X.; Cuong, L. V.; Vinh, H.; Waller, D.; Peto, T. E. A.; White, N. J. N. Engl. J. Med. 1996, 335, 76.
16. For an excellent overview see: Bruce-Chwatt, L. J. In Malaria: Principles and Practice of Malariology, Wernsdorfer, W. H., McGregor, I., Eds.; Churchill Livingstone: Edinburgh, 1988, Vol. 1, Chapter 1.
17. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
18. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
19. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
20. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
21. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
22. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
23. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
24. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Huaxue Xuebao 1983, 41, 574. Schmid, G.; Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624. Xu, X.-X.; Zhu, J.; Huang, D.-Z.; Zhou, W.-S. Tetrahedron 1986, 42, 819. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. Tetrahedron Lett. 1987, 28, 4629. Ravindranathan, T.; Kumar, M. A.; Menon, R. B.; Hiremath, S. V. Tetrahedron Lett. 1990, 31, 755. Avery, M. A.; Chong, W. K. M.; Jennings-White, C. J. Am. Chem. Soc. 1992, 114, 974. Lansbury, P. T.; Nowak, D. M. Tetrahedron Lett. 1992, 34, 4435. Liu, H.-J.; Yen, W.-L.; Chew, S. Y. Tetrahedron Lett. 1993, 34, 4435.
25. For reviews, see: Zaman, S. S.; Sharma, R. P. Heterocycles 1991, 32, 1593. Butler, A. R.; Wu, Y.-L. Chem. Soc. Rev. 1992, 85. Zhou, W.-S.; Xu, X.-X. Acc. Chem. Res. 1994, 27, 211.
26. For reviews, see: Zaman, S. S.; Sharma, R. P. Heterocycles 1991, 32, 1593. Butler, A. R.; Wu, Y.-L. Chem. Soc. Rev. 1992, 85. Zhou, W.-S.; Xu, X.-X. Acc. Chem. Res. 1994, 27, 211.
27. For reviews, see: Zaman, S. S.; Sharma, R. P. Heterocycles 1991, 32, 1593. Butler, A. R.; Wu, Y.-L. Chem. Soc. Rev. 1992, 85. Zhou, W.-S.; Xu, X.-X. Acc. Chem. Res. 1994, 27, 211.
28. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1789. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1792. Avery, M. A.; Chong, W. K. M.; Bupp, J. E. J. Chem. Soc., Chem. Commun. 1990, 1487. Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron Lett. 1990, 31, 1799. Avery, M. A.; Bupp, J. Internat. Pat. Applic. WO 91/14689, Oct 1991.
29. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1789. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1792. Avery, M. A.; Chong, W. K. M.; Bupp, J. E. J. Chem. Soc., Chem. Commun. 1990, 1487. Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron Lett. 1990, 31, 1799. Avery, M. A.; Bupp, J. Internat. Pat. Applic. WO 91/14689, Oct 1991.
30. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1789. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1792. Avery, M. A.; Chong, W. K. M.; Bupp, J. E. J. Chem. Soc., Chem. Commun. 1990, 1487. Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron Lett. 1990, 31, 1799. Avery, M. A.; Bupp, J. Internat. Pat. Applic. WO 91/14689, Oct 1991.
31. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1789. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1792. Avery, M. A.; Chong, W. K. M.; Bupp, J. E. J. Chem. Soc., Chem. Commun. 1990, 1487. Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron Lett. 1990, 31, 1799. Avery, M. A.; Bupp, J. Internat. Pat. Applic. WO 91/14689, Oct 1991.
32. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1789. Avery, M. A.; Jennings-White, C.; Chong, W. K. M. J. Org. Chem. 1989, 54, 1792. Avery, M. A.; Chong, W. K. M.; Bupp, J. E. J. Chem. Soc., Chem. Commun. 1990, 1487. Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron Lett. 1990, 31, 1799. Avery, M. A.; Bupp, J. Internat. Pat. Applic. WO 91/14689, Oct 1991.
33. Deng, D.; Zhu, D.; Gao, Y.; Dai, J.; Xu, R. Kexue Tongbao 1982, 27, 1359. Klayman, D. L.; Lin, A. J.; Acton, N.; Scovill, J. P.; Hoch, J. M.; Milhous, W. K.; Theoharides, A. D.; Dobek, A. S. J. Nat. Prod. 1984, 47, 715-717.
34. Deng, D.; Zhu, D.; Gao, Y.; Dai, J.; Xu, R. Kexue Tongbao 1982, 27, 1359. Klayman, D. L.; Lin, A. J.; Acton, N.; Scovill, J. P.; Hoch, J. M.; Milhous, W. K.; Theoharides, A. D.; Dobek, A. S. J. Nat. Prod. 1984, 47, 715-717.
35. Analysis of dried leaf samples provided by the Kunming Pharmaceutical Factory, Kunming, China, indicate concentrations of qinghao acid 3-fold less than those of qinghaosu. In contrast, the concentration of qinghao acid in A. annua samples from Shandong Province is reported at 3.8% dry wt (top leaves of the main stem): Huang, J.-J.; Zhou, F.-Y.; Wu, L. F.; Zhen, G.-H. Acta Chim. Sin. 1988, 383.
36. Haynes, R. K.; Vonwiller, S. C. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, Suppl. 1, S23.
37. Kim, N.-C; Kim, S.-U. J. Korean Agric. Chem. Soc. 1992, 35, 106.
38. See inter alia: Arain, M. F.; Haynes, R. K.; Vonwiller, S. C.; Hambley, T. W. J. Am. Chem. Soc. 1985, 107, 4582. Haynes, R. K.; Hilliker, A. E. Tetrahedron. Lett. 1986, 27, 509. Arain, M. F.; Haynes, R. K.; Vonwiller, S. C. Aust. J. Chem. 1988, 41, 505 and references therein.
39. See inter alia: Arain, M. F.; Haynes, R. K.; Vonwiller, S. C.; Hambley, T. W. J. Am. Chem. Soc. 1985, 107, 4582. Haynes, R. K.; Hilliker, A. E. Tetrahedron. Lett. 1986, 27, 509. Arain, M. F.; Haynes, R. K.; Vonwiller, S. C. Aust. J. Chem. 1988, 41, 505 and references therein.
40. See inter alia: Arain, M. F.; Haynes, R. K.; Vonwiller, S. C.; Hambley, T. W. J. Am. Chem. Soc. 1985, 107, 4582. Haynes, R. K.; Hilliker, A. E. Tetrahedron. Lett. 1986, 27, 509. Arain, M. F.; Haynes, R. K.; Vonwiller, S. C. Aust. J. Chem. 1988, 41, 505 and references therein.
41. During a visit to the Chinese Academy of Science Shanghai Institute of Organic Chemistry in June 1988, historical development of qinghaosu was related to R.K.H. in discussions with Professor Zhou Wei-Shan's group.
42. The significance of the stereochemistry of oxygen insertion into aldehyde 10 (Scheme 1) is discussed in ref 40.
43. For reviews, see: Frimer, A. A. Chem. Rev. 1979, 79, 363. Kropf, H. Methoden der Organischen Chemie (Houben-Weyl); Band E13, Organische Peroxoverbindungen; George Thieme Verlag: Stuttgart, 1988; Teilband II, Chapter B, pp 1084-1095 and references therein.
44. For reviews, see: Frimer, A. A. Chem. Rev. 1979, 79, 363. Kropf, H. Methoden der Organischen Chemie (Houben-Weyl); Band E13, Organische Peroxoverbindungen; George Thieme Verlag: Stuttgart, 1988; Teilband II, Chapter B, pp 1084-1095 and references therein.
45. Porter, N. A. In Organic Peroxides; Ando, W., Ed.; Wiley, New York, 1992; pp 143-146 and references therein.
46. Haynes, R. K.; Vonwiller, S. C. J. Chem. Soc., Chem. Commun. 1990, 449.
47. Courtneidge, J. L. J. Chem. Soc., Chem. Commun. 1992, 381.
48. We did not discount Hock cleavage as a possible route to the dicarbonyl compounds, as is assumed in ref 20 in a criticism of our work in ref 19.
49. Haynes, R. K.; Vonwiller, S. C J. Chem. Soc, Chem. Commun. 1990, 1102.
50. For biosynthetic conversions invoking Hock cleavage in fatty acid metabolism, see ref 18.
51. Morand, P.; Kaufman, M. J. Org. Chem. 1969, 34, 2175.
52. Haynes, R. K.; Vonwiller, S. C.; Warner, J. A. Unpublished results.
53. Haynes, R. K.; Vonwiller, S. C. J. Chem. Soc., Chem. Commun. 1990, 452.
54. 3 induces allylic hydroperoxide cleavage under both nitrogen and oxygen. It is ineffective as an oxygenation catalyst; see: Haynes, R. K.; King, G. R.; Vonwiller, S. C. J. Org. Chem. 1994, 59, 4743.
55. Vonwiller, S. C.; Warner, J. A.; Mann, S. T.; Haynes, R. K. J. Am. Chem. Soc. 1995, 117, 11098.
56. Acton, N.; Klayman, D. L. Planta Med. 1985, 441.
57. Acton, N.; Klayman, D. L. Planta Med. 1987, 266.
58. For an alternative approach to dehydroqinghaosu from qinghaosu, see: El-Feraly, F. S.; Ayalp, A.; A.;-Yahya, M. A.; McPhail, D. R.; McPhail, A. T. J. Nat. Prod. 1990, 53, 66.
59. Haynes, R. K.; Vonwiller, S. C. Provisional Patent P6989, September 1989. Haynes, R. K.; Vonwiller, S. C. Int. Applic. PCT/Au90/00456 (27/9/90) WO; Chem. Abstr. 1992, 116, 59094a. Haynes, R. K.; Vonwiller, S. C. Synlett 1992, 481. Haynes, R. K.; Vonwiller, S. C. PCT Int. Applic. WO 9308195 (29/4/93); Chem. Abstr. 1993, 119, 181047q. Haynes, R. K.; Vonwiller, S. C.; Wang, H.-J. Tetrahedron Lett. 1995, 36, 4641.
60. Haynes, R. K.; Vonwiller, S. C. Provisional Patent P6989, September 1989. Haynes, R. K.; Vonwiller, S. C. Int. Applic. PCT/Au90/00456 (27/9/90) WO; Chem. Abstr. 1992, 116, 59094a. Haynes, R. K.; Vonwiller, S. C. Synlett 1992, 481. Haynes, R. K.; Vonwiller, S. C. PCT Int. Applic. WO 9308195 (29/4/93); Chem. Abstr. 1993, 119, 181047q. Haynes, R. K.; Vonwiller, S. C.; Wang, H.-J. Tetrahedron Lett. 1995, 36, 4641.
61. Haynes, R. K.; Vonwiller, S. C. Provisional Patent P6989, September 1989. Haynes, R. K.; Vonwiller, S. C. Int. Applic. PCT/Au90/00456 (27/9/90) WO; Chem. Abstr. 1992, 116, 59094a. Haynes, R. K.; Vonwiller, S. C. Synlett 1992, 481. Haynes, R. K.; Vonwiller, S. C. PCT Int. Applic. WO 9308195 (29/4/93); Chem. Abstr. 1993, 119, 181047q. Haynes, R. K.; Vonwiller, S. C.; Wang, H.-J. Tetrahedron Lett. 1995, 36, 4641.
62. Haynes, R. K.; Vonwiller, S. C. Provisional Patent P6989, September 1989. Haynes, R. K.; Vonwiller, S. C. Int. Applic. PCT/Au90/00456 (27/9/90) WO; Chem. Abstr. 1992, 116, 59094a. Haynes, R. K.; Vonwiller, S. C. Synlett 1992, 481. Haynes, R. K.; Vonwiller, S. C. PCT Int. Applic. WO 9308195 (29/4/93); Chem. Abstr. 1993, 119, 181047q. Haynes, R. K.; Vonwiller, S. C.; Wang, H.-J. Tetrahedron Lett. 1995, 36, 4641.
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88. The conversion of enol 34 into dehydroqinghaosu (32) requires installation of three new chiral centers (cf. Scheme 1). Addition of oxygen to the Re-face of the enol radical 36 leading to hydroperoxide 30 is preferred because of the adjacent β-configured diaxial side chains. In 30, the hydroperoxy group is equatorial and the distal carbonyl group is accessible for both Re-face attack, leading to peroxyhemiacetal 31, and Si-face attack, leading to "unnatural" peroxyhemiacetal. As unnatural qinghaosu-like products are never observed, it is possible that equilibration of any unnatural hemiacetal precursor may occur via ring-opening and reclosure to the "natural" qinghaosu or precursor.
89. Rearrangement of hydroperoxide 26 to enol 34 is presumed to proceed via a cyclic enol ether (cf. compound 9, Scheme 1), an intermediate which we have so far not been able to detect.
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93. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
94. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
95. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
96. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
97. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
98. For varying views, see: Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 253. Haynes, R. K.; Vonwiller, S. C. Tetrahedron Lett. 1996, 37, 257. Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301. Posner, G. H.; Park, S. B.; Gonzalez, L.; Wang, D. S.; Cumming, J. N.; Klinedinst, D.; Shapiro, T. A.; Bachi, M. D. J. Am. Chem. Soc. 1996, 118, 3537 and references therein. For a recapitulation of results and interpretations described in the foregoing publications and propositions of chemically intriguing events and entities including suprafacial [1,2]-shifts of hydroxyl radicals and nonredox active Fe(II) see: Jefford, C. W.; Vicente, M. G. H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, Brunner, G.; Burger, U. Helv. Chim. Acta 1996, 79, 1475. For an additional viewpoint, see: Wu, W.-M.; Yao, Z.-J.; Wu, Y.-L.; Jiang, K.; Wang, Y.-F.; Chen, H.-B.; Shan, F.; Li, Y. J. Chem. Soc., Chem. Commun. 1996, 2213.
99. For activity of qinghaosu and derivatives against other targets, see inter alia: Xiao, S.-H.; Catto, B. A. Antimicrob. Agents Chemother. 1989, 33, 1557. Ou-Yang, K.; Krug, E. C.; Marr, J. J.; Berens, R. L. Antimicrob. Agents Chemother. 1990, 34, 1961. Merali, S.; Meshnick, S. R. Antimicrob. Agents Chemother. 1991, 35, 1225. You, J.-Q.; Mei, J.-Y.; Xiao, S.-H. Acta Pharm. Sin. 1992, 13, 280. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingré, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. T. J. Nat. Prod. 1993, 56, 849.
100. For activity of qinghaosu and derivatives against other targets, see inter alia: Xiao, S.-H.; Catto, B. A. Antimicrob. Agents Chemother. 1989, 33, 1557. Ou-Yang, K.; Krug, E. C.; Marr, J. J.; Berens, R. L. Antimicrob. Agents Chemother. 1990, 34, 1961. Merali, S.; Meshnick, S. R. Antimicrob. Agents Chemother. 1991, 35, 1225. You, J.-Q.; Mei, J.-Y.; Xiao, S.-H. Acta Pharm. Sin. 1992, 13, 280. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingré, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. T. J. Nat. Prod. 1993, 56, 849.
101. For activity of qinghaosu and derivatives against other targets, see inter alia: Xiao, S.-H.; Catto, B. A. Antimicrob. Agents Chemother. 1989, 33, 1557. Ou-Yang, K.; Krug, E. C.; Marr, J. J.; Berens, R. L. Antimicrob. Agents Chemother. 1990, 34, 1961. Merali, S.; Meshnick, S. R. Antimicrob. Agents Chemother. 1991, 35, 1225. You, J.-Q.; Mei, J.-Y.; Xiao, S.-H. Acta Pharm. Sin. 1992, 13, 280. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingré, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. T. J. Nat. Prod. 1993, 56, 849.
102. For activity of qinghaosu and derivatives against other targets, see inter alia: Xiao, S.-H.; Catto, B. A. Antimicrob. Agents Chemother. 1989, 33, 1557. Ou-Yang, K.; Krug, E. C.; Marr, J. J.; Berens, R. L. Antimicrob. Agents Chemother. 1990, 34, 1961. Merali, S.; Meshnick, S. R. Antimicrob. Agents Chemother. 1991, 35, 1225. You, J.-Q.; Mei, J.-Y.; Xiao, S.-H. Acta Pharm. Sin. 1992, 13, 280. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingré, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. T. J. Nat. Prod. 1993, 56, 849.
103. For activity of qinghaosu and derivatives against other targets, see inter alia: Xiao, S.-H.; Catto, B. A. Antimicrob. Agents Chemother. 1989, 33, 1557. Ou-Yang, K.; Krug, E. C.; Marr, J. J.; Berens, R. L. Antimicrob. Agents Chemother. 1990, 34, 1961. Merali, S.; Meshnick, S. R. Antimicrob. Agents Chemother. 1991, 35, 1225. You, J.-Q.; Mei, J.-Y.; Xiao, S.-H. Acta Pharm. Sin. 1992, 13, 280. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingré, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. T. J. Nat. Prod. 1993, 56, 849.