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Tesi etd-08072020-151259


Thesis type
Tesi di laurea magistrale
Author
RONCUCCI, DANIELE
URN
etd-08072020-151259
Title
New pentannulation strategies for the stereo-controlled synthesis of the isoprostanoids core
Struttura
CHIMICA E CHIMICA INDUSTRIALE
Corso di studi
CHIMICA
Supervisors
relatore Dott. Mandoli, Alessandro
Parole chiave
  • Isoprostanes
  • cyclization reactions
  • conjugate addition
  • organocatalysis
  • diastereoselectivity
  • Baldwin rules
Data inizio appello
14/09/2020;
Consultabilità
Parziale
Data di rilascio
14/09/2023
Riassunto analitico
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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