Methodology development for the synthesis of electronically poor (N4-aryl-N1-β-D-glucopyranosyl) cytosines

Postgraduate Thesis uoadl:2879683 267 Read counter

Unit:
Κατεύθυνση Οργανική Σύνθεση και Εφαρμογές της στη Χημική Βιομηχανία
Library of the School of Science
Deposit date:
2019-07-24
Year:
2019
Author:
Emmanouil Eirini
Supervisors info:
Αθανάσιος Γκιμήσης, Αναπληρωτής Καθηγητής, τμήμα Χημείας, ΕΚΠΑ
Original Title:
Ανάπτυξη νέων πρωτοκόλλων σύνθεσης ηλεκτρονιακά φτωχών N4-αρυλο-Ν1-(β-D-γλυκοπυρανοζυλο)κυτοσινών
Languages:
Greek
Translated title:
Methodology development for the synthesis of electronically poor (N4-aryl-N1-β-D-glucopyranosyl) cytosines
Summary:
The present thesis deals with the synthesis β-D-glucopyranosyl nucleosides,
potential inhibitors for the catalytic site of glycogen phosphorylase, a molecular
target for the development for antidiabetic drugs. The main target of the thesis
was the development of new synthetic protocols of N4-aryl-N1-(β-Dglucopyranosyl)cytosines,
where the aryl groups correspond to 2arylbenzimidazoles
or N-arylphthalimides.
The previous synthetic protocol, developed in our laboratory, that entailed the
substitution of an 1,2,4-triazolyl group at 4-position of protected
glucopyranosylpyrimidines by arylamines, adsorbed in silica gel or dissolved in
DMSO, was not efficient in the case of electronically poor arylamines.
For this reason, a first synthetic protocol was developed, where with the use of
acidic conditions, in the presence of the pivalic acid, the synthesis of Narylphtalimide
substituted glucopyranosylpyrimidines was effected in good
yields.
In a second synthetic approach, we developed a protocol based on a BuchwaldHartwig
reaction between a protected β-D-glucopyranosylcytosine and
aryliodides in a presence of palladium catalyst. The polarity reversal in the
system allowed the use of electronically poor aryliodides in the coupling
reaction, obtaining final products similar with the ones obtained under the
previous synthetic protocol.
Finally, substitution of the 1,2,4-triazolyl group in the 4-position of protected
glucopyranosylpyrimidines by malonates lead to the synthesis of a new family
of potential inhibitors of glycogen phosphorylase.
Main subject category:
Science
Keywords:
Inhibitors, glycogen phosphorylase, 2-aryl-6-aminobenzimidazoles, N-aryl-4-aminophthalimides, Umpolung
Index:
Yes
Number of index pages:
2
Contains images:
Yes
Number of references:
67
Number of pages:
169
Ανάπτυξη νέων πρωτοκόλλων σύνθεσης ηλεκτρονιακά φτωχών Ν4-αρυλο-Ν1-(β-D-γλυκοπυρανοζυλο)κυτοσινών.pdf (6 MB) Open in new window