• Isoprostani
• Organometalli
• Organocatalisi
• Sintesi stereoselettiva
• Cicloaddizioni [3+2]
• Addizione coniugata
• Ciclopentanellazione

Five-membered rings are ubiquitous in natural and biologically relevant products. Among the plethora of known compounds, an important class consists of the prostaglandins (PGs), which are oxygenated cyclopentane derivatives endowed with remarkable bio-activity towards various systems (e.g. cardio-vascular, gastro-intestinal, etc.). In the past decades, much interest was attracted by some stereoisomers of the prostaglandins. In particular, the isoprostanes (IsoPs) are a family of prostaglandin-like compounds, which are formed in vivo by the non-enzymatic oxidative cyclization of polyunsaturated fatty acids under oxidative stress conditions. The peculiar stereochemical feature of the most representative compounds in the IsoP class is the cis relationship between the carbon side chains protruding from the cyclopentane core. These compounds are analytically relevant, being biomarkers for several human diseases and exerting different biological activities as well.
In this Thesis work, three new synthetic routes were investigated for the diastereoselective preparation of functionalized cyclopentane building-blocks, susceptible to further elaboration into prostanoidic derivatives.
The first approach envisaged domino Michael/intramolecular α-alkylation reaction between ethyl-4-chloroacetoacetate and 2-cyclopentenone. The second approach involved the initial synthesis of 3,4-epoxycycloalkanones and their subsequent proline-promoted cyclization. Unfortunately, due to different reasons all these attempts were largely ineffective, but nonetheless set a convenient experimental background for further developments in this laboratory.
The third approach made use of synthetic equivalents of trimethylenemethane. In a first embodiment of the idea, allyl functionalized organometallic reagents (magnesium, zinc and indium) were briefly examined. Finally, the last part of the Thesis involved the synthesis of alkylidenecyclopropanes and the study of their metal-catalyzed [3+2] cycloaddition reactions with olefins. Contrarily to literature precedents, mainly from the Binger’s group in Germany, in our hands the Ni- or Pd-catalyzed reactions were unsatisfactory when applied to unsaturated substrates of interest for the preparation of IsoPs. In spite of this, several experimental observations could be made in the present work, which opened the way to understanding the reasons of the experimental shortcomings and provided hints for their solution.