Chemistry, Department of


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A DISSERTATION Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Doctor of Philosophy, Major: Chemistry, Under the Supervision of Professor Patrick H. Dussault. Lincoln, Nebraska: June, 2011

Copyright 2011 Charles E. Schiaffo


The use of ozone for the transformation of alkenes to carbonyls has been well established. The reaction of ozone with alkenes in this fashion generates either a 1,2,4-trioxolane (ozonide) or a hydroperoxyacetal, either of which must undergo a separate reduction step to provide the desired carbonyl compound. There is considerable interest in being able to perform a reductive ozonolysis to directly provide the carbonyl. Previous reports from the Dussault lab have shown that amine N-oxides are able to perform a reductive ozonolysis. In the course of efforts to expand this reaction to other oxyanions it was realized that water was also able to efficiently perform a net reductive ozonolysis via nucleophilic capture of the carbonyl oxide. This transformation was investigated for a variety of substrates and was shown to offer a useful alternative to conventional ozonolysis conditions.

Malaria is a global health epidemic that affects between 300-500 million people annually, with the most deadly strain being P. falciparum. The current treatment for malaria is artemisinin combination therapy, but the development of artemisinin-resistant strains of malaria has spurred the need for the development of new treatments. 1,2,4- Trioxolanes exhibit high efficacy against malaria, but concerns remain about their thermal and serum stability. Our analysis of the likely mechanism of action of ozonides guided our development of structurally related 3-alkoxy-1,2-dioxolanes as a potential treatment for malaria. This class of compounds has shown to possess high levels of activity against P. falciparum in vitro. The synthesis of these dioxolanes required the development of new synthetic routes, which will be discussed in detail, as will efforts to optimize the activity of 3-alkoxy-1,2-dioxolanes. In addition, the synthesis and evaluation of 1,2,4-trioxepanes as potential antimalarials was explored.

In the course of our investigation into the synthesis of 3-alkoxy-1,2-dioxolanes, we found Re (VII) oxide to be an effective catalyst for the transetherification of 3-alkoxy-1,2-dioxolanes. Re (VII) oxide was briefly explored as a catalyst for allylation or etherification reactions that involve stabilized carbocations as intermediates.

Advisor: Patrick H. Dussault