Synthesis of atovaquone

Tetrahedron Letters

Volumn 39, Issue 42, 1998, Pages 7629-7632

  Williams, David R ^a   Clark, Michael P ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATOVAQUONE;

ANTIFUNGAL ACTIVITY; ANTIMALARIAL ACTIVITY; ARTICLE; DRUG CONFORMATION; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

EID: 0032532799     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01691-8     Document Type: Article

References (19)

1. 1. For an overview: (a) Thomson, R. H. Naturally Occuring Quinones; 3rd ed.; Chapman and Hall: London, 1987.
2. (b) Patai, S.; Rappoport, Z. Eds.; The Chemistry of Quinonoid Compounds; John Wiley and Sons: New York, 1988, Vol. 2.
3. (c) Finley, K. T. Supplement E: The Chemistry of Hydroxyl, Ether and Peroxide Groups; Patai, S. Ed.; John Wiley and Sons: New York, 1993, Vol. 2, pp 1027-1134.
4. 2. (a) Cirioni, O.; Giancometti, A.; Balducci, M.; Burzacchini, F.; Scalise, G. J. Antimicrob. Chemother. 1995, 36, 740.
5. (b) Comley, J. C. W.; Yeates, C. L.; Frend, T. J. Antimicrob. Agents Chemother. 1995, 39, 2217.
6. 3. Atovaquone is a prescription pharmaceutical manufactured by Glaxo-Wellcome under the trade name Mepron®. Hudson, A. T.; Yeates, C. L. E.P. Patent 445141, 1996. Hudson, A. T.; E.P. Patent 634996 A1, 1996.
7. 4. (a) Antimalarial agent: Looareesuwan, S.; Viravan, C.; Webster, H.; Kyle, D. E.; Hutchinson, D. B.; Canfield, C. J. Am. J. Trop. Med. Hyg. 1996, 54, 62.
8. (b) Toxoplasmosis: Araujo, F. G.; Suzuki, Y.; Remington, J. S. Eur. J. Clin. Microbiol Infect. 1996, 15, 394.
9. (c) Babesiosis: Hughes, W. T.; Oz, H. S. J. Infect. Dis. 1995, 172, 1042.
10. 5. Hammond, D. J.; Burchell, J. R.; Pudney, M. Mol. Biochem. Parasitol. 1985, 14, 97.
11. 3) δ 158.7, 157.7, 144.0, 131.9, 128.6, 128.1, 77.3, 42.4, 31.9, 31.4.
12. 7. For related studies: Cory, R. M.; Walker, J. R.; Zabel, P. D. Synth. Commun. 1994, 24, 799.
13. 8. Stronger acids and/or higher reaction temperatures will contribute to the elimination (TsOH; toluene at reflux).
14. 9. Suzuki, H.; Tani, H.; Kubota, H; Sato, N.; Tsuji, J.; Osuka, A. Chem. Lett. 1992, 1299.
15. 10. Jacobsen, N.; Goldman, J.; Torssell, K. Acta Chemica Scandinavica 1974, 528, 492.
16. 11. Our efforts for coupling of 4-(4-chlorophenyl)cyclohexane-1-carboxylic acid (13) and 8 gave yields of 9 ranging from 10 to 14%. Reference 3 describes the oxidation of 13 to yield 7% of 9.
17. 12. Minisci, F.; Lazzarini, E.; Fontana, F.; Coppa, F. Chem. Lett. 1992, 1299.
18. 10) ammonium chloride (Aldrich). One drop of phase-transfer catalyst was used per 5 mL of solution.
19. 14. We gratefully acknowledge the assistance of Dr. Martin Osterhout (Glaxo-Wellcome) in obtaining a sample of atovaquone as well as NMR spectra for our comparisons.