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Tesi etd-03022015-182424


Thesis type
Tesi di laurea magistrale
Author
CRISTOFORI, VIRGINIA
URN
etd-03022015-182424
Title
studi rivolti alla sintesi di (-)-nutlin-3
Struttura
CHIMICA E CHIMICA INDUSTRIALE
Corso di studi
CHIMICA
Commissione
relatore Carpita, Adriano
relatore Trapella, Claudio
controrelatore Iuliano, Anna
Parole chiave
  • Enantiosective Synthesis Dual-cathalysis Nutlin Ca
Data inizio appello
14/04/2015;
Consultabilità
completa
Riassunto analitico
Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2−p53 protein− protein interaction (PPI) has been pursued as a new anti-cancer therapeutic strategy. The best documented class of compounds, cis-imidazolines (named Nutlins), are selective and potent inhibitors, and selected examples exhibit potency in the nanomolar range. The eutomer (-)-Nutlin-3 induce apoptosis in p53 wild-type cells and show in vivo efficacy in mice xenograft models.<br>Herein we briefly summarized the main methods for the synthesis of (±)-Nutlin-3 and its derivatives, and we described the enantioselective way for preparing (-)-Nutlin-3.<br>We also identified an asymmetric, economic and simple route for the desymmetrization of a stilben-meso-diamine as a direct precursor of (-)-Nutlin-3. The desymmetrization is based on a dual-catalytic approach with DMAP and a chiral thiourea that act as a Hydrogen-Bonding Catalyst. Part of the work has been done for the optimization of the reaction conditions in order to improve yield and enantiomeric excess.
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