Dioxiranes and bioactive molecules: Selective oxyfunctionalization of vitamin D synthons, linear peptides, and cyclosporins

Dimethyldioxirane and methyl(trifluoromethyl)dioxirane are effective reagents to carry out a variety of synthetically useful oxidations. Because of their very mild reaction conditions, they are the reagents of choice to achieve the oxidation of labile compounds and of natural products.;This thesis reports some interesting examples of selective oxyfunctionalization of biologically relevant molecules by dioxiranes.;The first chapter is focused on the conversion of epoxy alcohols into the corresponding epoxy ketones. Epoxy ketones are useful building blocks in organic synthesis.;The second chapter describes the reactivity of methyl(trifluoromethyl)dioxirane with representative Boc-protected and acetyl-protected peptide methyl esters bearing alkyl side chains. The described reactions give easy access to valuable synthons in hydroxamic acids and polypeptides preparation and can be used in the development of peptide derivatives that are therapeutically useful.;The third chapter reports the oxyfunctionalization of cyclosporine, that is a potent immunosuppressant. It is also effective in the treatment of many immunoregulatory dysfunctions. However, its clinical use is associated with toxic side effects.;The selective oxyfunctionalization of cyclosporine by dioxiranes is interesting for several reasons. Introducing new functionalities on cyclosporine by dioxiranes might improve the bioavailability and/or the pharmacological profile of this drug. It will also provide useful insight into the metabolic fate of the parent molecule, since it allows the access to the labile cyclosporine-epoxide. It has been hypothesized that the formation of certain cyclosporine metabolites occurs through the generation of a common cyclosporine metabolite intermediate, the cyclosporine-epoxide. The availability of cyclosporineepoxide as isolated compound will provide the opportunity to support or eliminate this hypothesis.;The description of dihydrocyclosporine acetate is also reported in the third chapter, and its oxidation by methyl(trifluoromethyl)dioxirane is described. Even in a complex system as dihydrocyclosporine acetate, methyl(trifluoromethyl)dioxirane provides outstanding selectivity, producing just one major product, the gamma-hydroxy-MeLeu4 derivative. Therefore this chapter includes also a remarkable example of outstanding selectivity in organic synthesis, achieved by dioxirane.