• isoprostanes
• prostaglandins
• silylenolethers
• organoindium
• Grignard
• conjugate addition
• ketene acetals
• Nakamura
• oxidative cyclization
• cyclopentannulation

The isoprostanes (IsoPs) are a family of prostaglandin-like compounds, which are formed in vivo by the non-enzymatic oxidative cyclization under oxidative stress conditions of polyunsaturated fatty acids (PUFAs). The majority of the products in this class bear the distinctive stereochemical feature of possessing a cis relationship, between the side chains that protrude from mono- or dioxygenated cyclopentane core. Moreover, it is noteworthy the cis configuration of the hydroxy substituents in the derivatives, belonging to the isoprostane F-family. These compounds are analytically relevant, being bio-markers for several human diseases, and can exert different biological activities as well.
Hence, in this Thesis work, new routes were investigated for the diastereoselective preparation of functionalized cyclopentane building-blocks, amenable to further elaboration into prostanoidic derivatives. With this aim, new cyclopentannulation routes were explored by following two widely different synthetic schemes.
The first approach involved the initial conjugate addition of functionalized allyl-metal reagents (indium and magnesium) to 2-cyclopentenones, under two different protocols (Lipshutz-Hackmann and Lee et al.). Then, the cyclization of the resulting 3-allylcyclopentanone (or the corresponding silylenolether) was tackled, by resorting to vanadium- and palladium-promoted oxidative chemistry. Unfortunately, all these attempts along this route were largely ineffective, with only traces of the desired cyclized product obtained even in the best cases.
Much better results were obtained by following the alternative strategy, based on the thermal cycloaddition of the Nakamura’s methylenecyclopropane to electronpoor olefins and subsequent oxidation with dimethyldioxirane of the resulting ketene acetals. Building on the findings of an ongoing Ph.D. study, the present Thesis work addressed the substrate scope to some larger extent and prepared a number of new, densely funcionalized cyclopentane derivatives, which were characterized by the combination of GC-MS and mono- and bidimensional NMR techniques.