Unit:
Κατεύθυνση Οργανική ΧημείαLibrary of the School of Science
Author:
Ρούτης Βασίλειος-Μελέτιος
Supervisors info:
Δημήτριος Γεωργιάδης Επίκ. Καθηγητής
Original Title:
Διερεύνηση στερεοεκλεκτικών προσεγγίσεων σύνθεσης φωσφινικών ψευδοπεπτιδικών κορμών
Translated title:
Investigation stereoselective synthesis approaches phosphonates pseudo peptide logs
Summary:
The synthesis of stereochemically defined phosphinic peptides, a class of
metalloenzyme inhibitors that act as transition state analogues, is a highly
important target since optimization of their biological activity relies heavily
on specific stereochemical requirements. The lack of general methods for the
asymmetric insertion of side chain groups at P1 and P1’ positions hampers the
synthesis of such molecules.
At this work, the results of our extensive research efforts on the
stereochemical control of P1΄ position of derivatives II are presented. First,
P-alkylation of H-phosphinic esters with a variety of chiral halides was
investigated but without any positive result. Next, we focused on the Evans
chemistry that makes use of oxazolidinone as chilar auxiliaries for the
diastereoselective α-alkylation of substrates such as III. Unfortunately,
alkylation of substrates III to IV was unsuccessful due to the unexpected
extensive oxazolidinone cleavage. Then, based on Myers chemistry, we considered
the use of ephedrine as a chilar auxiliary. It was observed that the use of
this amide auxiliary is stable under alkylation conditions, unlike imide type
oxazolidinones. In addition, the use of ephedrine which is cheaper than
pseudoephedrine, not only afforded alkylated substrates VI in high conversion
yields but resulted in excellent diastereomeric ratios with a variety of R1΄
groups. Those preliminary results are expected to set the basis for a reliable
protocol concerning the stereochemical control of P1΄ position of phosphinic
peptides.
Keywords:
Organic Synthesis, Oxazolidinone, Ephedrine, Stereoselectivity, Phosphinic Acid
Number of references:
124
File:
File access is restricted.
document.pdf
5 MB
File access is restricted.
