Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική ΒιομηχανίαLibrary of the School of Science
Supervisors info:
Δημήτριος Γεωργιάδης, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Βικτωρία Μαγκριώτη, Αναπληρώτρια Καθηγήτρια, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Χριστόφορος Κόκοτος, Αναπληρωτής Καθηγητής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Διερεύνηση της Καταλυόμενης από οξύ Lewis Στερεοεκλεκτικής P-Mannich Αντίδρασης για τη Σύνθεση Φωσφινοδιπεπτιδίων
Translated title:
Investigation of Stereoselective P-Mannich Reaction Catalysed by Lewis Acid for the Synthesis of Phosphinic Dipeptides
Summary:
The P-Mannich reaction is an extremely useful synthetic tool in the field of organophosphorus analogues of amino acids. The successful outcome of this reaction is highly dependent on the reactivity of phosphorus nucleophiles, their valence state [Ρ(ΙΙΙ) or Ρ(V)] and the applied type of catalysis which must be compatible with the stability of the often sensitive P-nucleophiles. In addition, the stereoselective synthesis of organophosphorus amino acid analogues constitutes one of the main challenges in the field due to their significance as structural units of bioactive compounds.
Recently, our research team developed an acid-catalyzed protocol for the synthesis of α-aminophosphinic acids that is based on cyclic mixed anhydrides, in situ formed from β-phosphinyl propionic acids. The high reactivity of these derivatives renders them extremely useful synthetic intermediates for the assembly of aminophosphinic acids and, in particular phosphinic peptides, a class of compounds that has found wide application to the synthesis of phosphinopeptidic enzyme inhibitors. As an extension of the aforementioned methodology, the use of these intermediates to the stereoselective Ρ-Mannich reaction with chiral imines is studied in the present thesis. The proposed methodology leads to high stereoselectivities (d.r. 90:10 up to >99:1) and allows the one-step stereoselective assembly of the aminophosphinic unit found in the P1 position of phosphinic dipeptides, according to the principles of late-stage diversification. These preliminary results are expected to form the basis for a general and reliable methodology towards the stereoselective late-stage diversification of aminophosphinic units within phosphinopeptidic building blocks.
Main subject category:
Science
Keywords:
Organic Synthesis, Late-stage diversification, Phosphinic Acid, Mannich, Imine
Number of references:
139
