Synthesis of C-glucopyranoside analogues of natural nucleosides with potential pharmaceutical activity"

Postgraduate Thesis uoadl:1320130 363 Read counter

Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική Βιομηχανία
Library of the School of Science
Deposit date:
2016-03-09
Year:
2016
Author:
Μαυρέας Κωνσταντίνος-Φιοραβάντες
Supervisors info:
Γκιμήσης Αθανάσιος Αναπληρωτής Καθηγητής (Επιβλέπων), Δημήτρης Γεωργιάδης Επίκ. Καθηγητής Γεώργιος Βουγιακαλάκης Λέκτορας
Original Title:
Σύνθεση C-γλυκοπυρανοζυλο-αναλόγων φυσικών νουκλεοζιτών με πιθανή φαρμακολογική δράση
Languages:
Greek
Translated title:
Synthesis of C-glucopyranoside analogues of natural nucleosides with potential pharmaceutical activity"
Summary:
Type 2 diabetes has been rapidly reaching the proportions of a global epidemic
in
recent years. Our laboratory has been active in this research field with the
synthesis
and further study of numerous N-β-D-glucopyranosides of modified pyrimidines
exhibiting inhibitory effects on Glycogen Phosphorylase, an enzyme exceedingly
involved in the pathogenesis of type 2 diabetes, as potential therapeutic
agents.
In this diplomatic thesis the synthesis of new molecules with the general
structure of
pyrimidinyl C-glucopyranosides, having as a target the synthesis of molecules
with
similar structures to already known inhibitors, with improved pharmacological
properties,
as similarly structured drug molecules (e.g. Dapagliflozin).was studied. The
natural Cnucleoside
pseudoruridine was used as an example, as uridine did for inhibitors thus far
synthesized.
Utilizing published methods from the synthesis of pseudouridine, and combining
them
with the increasingly common method of β-C-glucopyranoside synthesis by
organosilane-Lewis acid stereoselective reduction, the synthesis of β-
C-glucopyranosyl
analogue of pseudouridine was studied and accomplished, as shown in the
graphical
abstract, as well as the synthesis of a further analogue designed to allow for
further
chemical modification, leading to the synthesis of a new group of drug molecule
candidates. Following additional kinetic and crystallographic studies, the
founding of a
new category of new, biologically more stable and antidiabetically active
molecules is
anticipated.
Keywords:
Diabetes, Glucogen Phosphorylase, Pseudouridine, C-glucopyranosyl-pyrimidines, Silane
Index:
Yes
Number of index pages:
12-15, 99-100
Contains images:
Yes
Number of references:
70
Number of pages:
154
File:
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