960121-33-9Relevant academic research and scientific papers
Spiro- and dispiro-1,2-dioxolanes: Contribution of iron(II)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides
Wang, Xiaofang,Dong, Yuxiang,Wittlin, Sergio,Creek, Darren,Chollet, Jacques,Charman, Susan A.,Tomas, Josefina Santo,Scheurer, Christian,Snyder, Christopher,Vennerstrom, Jonathan L.
, p. 5840 - 5847 (2007)
Fourteen spiro- and dispiro-1,2-dioxolanes were synthesized by peroxycarbenium ion annulations with alkenes in yields ranging from 30% to 94%. Peroxycarbenium ion precursors included triethylsilyldiperoxyketals and -acetals derived from geminal dihydroperoxides and from a new method employing triethylsilylperoxyketals and -acetals derived from ozonolysis of alkenes. The 1,2-dioxolanes were either inactive or orders of magnitude less potent than the corresponding 1,2,4-trioxolanes or artemisinin against P. falciparum in vitro and P. berghei in vivo. In reactions with iron(II), the predominant reaction course for 1,2-dioxolane 3a was two-electron reduction. In contrast, the corresponding 1,2,4-trioxolane 1 and the 1,2,4-trioxane artemisinin undergo primarily one-electron iron(II)-mediated reductions. The key structural element in the latter peroxides appears to be an oxygen atom attached to one or both of the peroxide-bearing carbon atoms that permits rapid β-scission reactions (or H shifts) to form primary or secondary carbon-centered radicals rather than further reduction of the initially formed Fe(III) complexed oxy radicals.
