Κατεύθυνση Οργανική Χημεία
Library of the School of Science

2016-10-19

2016

Παπαθανασοπούλου Μυρτώ

Δημήτριος Γεωργιάδης Αναπλ. Καθηγητής

Διερεύνηση Διαστερεοεκλεκτικότητας κατά τη Σύνθεση Ρ1΄-Ισοξαζολυλο-Υποκατεστημένων Φωσφινικών Διπεπτιδίων μέσω Προσθήκης P-Michael

Greek

Investigation of Diastereoselectivity during the Synthesis of P1΄-Isoxazol Substituted Phosphinic Dipeptides via P-Michael Addition

At this thesis, the structural factors and reaction conditions that control
diastereoselectivity of P-Michael reactions between aminophosphinic acids and
acrylic esters, that is the most popular reaction for preparing phosphinic
dipeptides, are being explored. It was found that the presence of isoxazole
rings at P1΄ position can lead to high diastereoselectivities for R,S isomer.
This can be further improved in the case of acrylic benzylesters (dr: 6:1).
Such rings have significant biological value since they are included in a
number of inhibitors for various enzymes. After optimization of solvent and
temperature it was discovered that diastereoselectivity can be increased to
18:1 using DMF at 4 C. Investigation of a variety of different acrylic esters
led to the observation that diphenylmethyl ester can produce an impressive d.r.
of 53:1. Finally, a strong epimerization effect was observed for the first time
in such type of structures, which is dependent on the nature of ester and can
reach to 96%. A putative mechanism is proposed which involves a cyclic
intermediate between the phosphinic acid and carboxylic acid group. The results
of this study are expected to set the basis for a reliable protocol for the
stereochemical control of P1΄ position of phosphinic peptides.

Organic Synthesis, Stereoselectivity, Epimerization, P-Michael, Phosphinic Acid

Yes

1-8

Yes

103

140

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https://pergamos.lib.uoa.gr/uoa/dl/object/1316829