ETD

Archivio digitale delle tesi discusse presso l'Università di Pisa

Tesi etd-08072020-151259


Tipo di tesi
Tesi di laurea magistrale
Autore
RONCUCCI, DANIELE
URN
etd-08072020-151259
Titolo
New pentannulation strategies for the stereo-controlled synthesis of the isoprostanoids core
Dipartimento
CHIMICA E CHIMICA INDUSTRIALE
Corso di studi
CHIMICA
Relatori
relatore Dott. Mandoli, Alessandro
Parole chiave
  • Isoprostanes
  • diastereoselectivity
  • cyclization reactions
  • conjugate addition
  • Baldwin rules
  • organocatalysis
Data inizio appello
14/09/2020
Consultabilità
Completa
Riassunto
The isoprostanes (IsoPs) are a family of prostaglandin-like compounds that form in vivo by the non-enzymatic oxidative cyclization of polyunsaturated fatty acids (PUFAs) under oxidative stress conditions. The distinctive stereochemical feature of the most representative compounds in this class is the cis relationship between the side chains that protrude from a common mono or dioxygenated cyclopentane core, as well as the cis configuration of the hydroxy substituents in the derivatives that belong to the isoprostane family.
Given the analytical relevance of the IsoPs as bio-markers for a number of pathological conditions, in this Thesis work new routes were explored for the diastereoselective preparation of functional cyclopentane building-blocks, amenable of further elaboration into prostanoidic derivatives. The general synthetic scheme adopted for this purpose involved the initial conjugate addition of allyl metal reagents to cyclopent-2-enones under Lipshutz conditions, followed by the functionalization of the allyl C––C double bond (if required), and a final cyclization step. For the latter stage alternative strategies were examined, viz. the olefin+silylenolether oxidative cyclization, the intramolecular alkylation of an enolate, and the proline-promoted cyclization of cyclopentanones bearing an epoxy side chain. While the former two approaches proved to be essentially useless, the latter afforded moderate yields of the desired products (40-42%), in a hiterto unknown enamine+epoxide cyclization process.
The connectivity and the relative configuration of the stereocenters in the oxy-functionalyzed bicyclo[3.3.0]octane derivatives from these organocatalytic reaction runs were fully characterized by mono- and bi-dimensional NMR techniques.
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