A new diastereoselective route to F-type Isoprostanes

The Isoprostanes (IsoPs) are naturally occurring compounds generated in vivo by the free-radical oxidation of polyunsaturated fatty acids. Thanks to their mechanism of formation, the IsoPs are among the best biomarkers to assess oxidative stress (OS), a condition known to be involved in the onset and progression of several human and animal pathologies. Moreover, preliminary studies demonstrated that these compounds exert a significant biological activity, which prompts intense investigations on their potential pharmaceutical applications. Both the aforementioned goals require the availability of adequate, and possibly cheap, synthetic standards. In this M.Sc. Thesis work, a new diastereoselective route to F-type IsoPs has been developed by optimizing the metal-catalyzed [3+2] pentanullation reaction between a cyclopropane reactant and a suitably protected cyclopentene substrate. By these means, a versatile synthetic intermediate, structurally related to the Rokach-Galano-Duran lactone, could be obtained, which was then converted into racemic F2t-IsoP and epi-F2t-IsoP. The stereochemical course in the [3+2] reaction stage was further confirmed by X-ray diffraction on crystals obtained from the deprotected cycloadduct