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Full-Text Articles in Physical Sciences and Mathematics
Synthesis And Antimalarial Activity Of Sixteen Dispiro-1,2,4,5-Tetraoxanes: Alkyl-Substituted 7,8,15,16-Tetraoxadispiro[5.2.5.2]Hexadecanes, Jonathan L. Vennerstrom, Yuxiang Dong, Walter Reed Army Institute Of Research, Arba L. Ager Jr., Hong-Ning Fu, Sheri M. Walters, James K. Wood, Geoffrey Edwards, Alexandra D. Holme, W. Graham Mclean
Synthesis And Antimalarial Activity Of Sixteen Dispiro-1,2,4,5-Tetraoxanes: Alkyl-Substituted 7,8,15,16-Tetraoxadispiro[5.2.5.2]Hexadecanes, Jonathan L. Vennerstrom, Yuxiang Dong, Walter Reed Army Institute Of Research, Arba L. Ager Jr., Hong-Ning Fu, Sheri M. Walters, James K. Wood, Geoffrey Edwards, Alexandra D. Holme, W. Graham Mclean
Chemistry Faculty Publications
Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in H2-SO4/CH3CN or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as single stereoisomers, whereas the five tetraoxanes formed without the stereochemical control provided by alkyl groups at the 1 and 10 positions were isolated as mixtures of diastereomers. Three of the sixteen …
Methyl-Substituted Dispiro-1,2,4,5-Tetraoxanes: Correlations Of Structural Studies With Antimalarial Activity, Kevin J. Mccollough, James K. Wood, Walter Reed Army Institute Of Research, Yuxiang Dong, Jonathan L. Vennerstrom
Methyl-Substituted Dispiro-1,2,4,5-Tetraoxanes: Correlations Of Structural Studies With Antimalarial Activity, Kevin J. Mccollough, James K. Wood, Walter Reed Army Institute Of Research, Yuxiang Dong, Jonathan L. Vennerstrom
Chemistry Faculty Publications
Two tetramethyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15,16-tetraoxadispiro[5.2.5.2]- hexadecanes) 3 and 4 were designed as metabolically stable analogues of the dimethylsubstituted dispiro-1,2,4,5-tetraoxane prototype WR 148999 (2). For a positive control we selected the sterically unhindered tetraoxane 5 (7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecane), devoid of any substituents. Tetraoxanes 3 and 4 were completely inactive in contrast to tetraoxanes 2 and 5. We hypothesize that the two inactive tetraoxanes possess sufficient steric hindrance about the tetraoxane ring due to the two additional axial methyl groups to prevent their activation to presumed parasiticidal carbon radicals by inhibiting electron transfer from heme or other iron(II) species. For each of the tetraoxanes 2-4, …