Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική ΒιομηχανίαLibrary of the School of Science
Author:
Ziotopoulou Angeliki
Supervisors info:
Δημήτριος Γεωργιάδης, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Βικτωρία Μαγκριώτη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Σταματία Βασιλείου, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
H Χρήση της Εφαιναμίνης και Ισομερών της στην Ασύμμετρη Αλκυλίωση β-Φωσφινυλο Καρβοξυλικών Παραγώγων
Translated title:
The Use of Ephenamine and its Isomers in the Asymmetric Alkylation of β-Phosphinyl Carboxylic Derivatives
Summary:
Phosphinic acids constitute an important class of bioactive compounds and the incorporation of such groups in short peptide chains is a successful strategy towards the development of inhibitors of enzymes (e.g. metalloproteases, aspartyl proteases). The enhanced bioactivity of these compounds depends on their stereochemical features, thus methods aiming to their stereoselective synthesis are necessary. The development of such methods presents significant synthetic challenges and the discovery of practical approaches for the production of stereochemically defined phosphinopeptidic compounds is a field of intense research activity.
To this respect, the main objective of the present thesis is the asymmetric alkylation of β-phoshinyl propionic derivatives, structural units of phosphinopeptidic building blocks. The proposed methodology is also suitable for the late-stage diversification of P1΄ position of target compounds, providing stereoselective access to a large variety of compounds. In particular, the use of ephenamine-based chiral auxiliaries was evaluated and the most efficient isomers in terms of yield and stereoselectivity were identified. The scope and limitations of the proposed methodology are described and useful conclusions for the generality of the method and the suitability of selected auxiliaries were drawn. The results described in this thesis are expected to guide future studies from our laboratory towards the development of a reliable and general method for the stereoselective alkylation of β-phosphinyl propionic scaffolds.
Main subject category:
Science
Keywords:
Organic Synthesis, Ephenamine, Alkylation, Stereoselectivity, Phosphinic Acid
Number of references:
158
