Priprava novih meta i para supstituiranih piridinonskih alfa-manozida i njihov antiadhezijski učinak

master's thesis

• Title (english): Preparation of Novel meta and para Substituted Pyridinone alpha-Mannosides and their Anti-adhesion Activity
• Author: Mateja Matišić
• Mentor: Vesna Petrović Peroković (mentor)
• Committee member: Vesna Petrović Peroković (predsjednik povjerenstva)
• Committee member: Sanda Rončević (član povjerenstva)
• Committee member: Biserka Prugovečki (član povjerenstva)
• Committee member: Srđanka Tomić-Pisarović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2018-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom diplomskom radu opisane su sinteze meta i para supstituiranih N-aril-3-
hidroksipiridin-4-ona (3-7) i njihovih α-D-manozida (13-16). Piridinonski prekursori 3-7
priređeni su modificiranom Harrisovom metodom iz 5-benziloksipiran-4-on-2-karboksilne
kiseline (2), dobivene iz komercijalno dostupne kojične kiseline, i odgovarajućih anilina (m- i
p-metilanilina, m- i p-nitroanilina te m-metoksianilina) uz dodatak kiselog katalizatora (p-
TsOH) zagrijavanjem u zatvorenoj teflonskoj posudi (autoklav). Spojevi 3-7 prevedeni su u
acetilirane manozne derivate (8-11) pomoću 2,3,4,6-tetra-O-acetil-1-brom-α-D-manopiranoze
uz AgOTf kao promotor i kolidin (Koenigs-Knorrova metoda glikozidacije). Uklanjanjem
acetatnih skupina s manozne podjedinice spojeva 8-11 Zemplénovim postupkom priređene su
ciljne molekule, N-aril-3-hidroksipiridin-4-onskih α-manozidi (13-16), kojima je ispitan
inhibitorski učinak u procesu adhezije E. coli na stanice eritrocita.
Strukture svih priređenih spojeva određene su spektroskopijom NMR (1H i 13C) i
spektrometrijom masa (MS).

Abstract (english)

In this diploma thesis the syntheses of meta and para substituted N-aryl 3-hydroxypyridin-4-
ones (3-7) and their α-D-mannosides (13-16) are described. Pyridinone precursors 3-7 were
prepared by Harris method from 5-benzyloxypyran-4-one-2-carboxylic acid (2) and
corresponding anilines (m- and p-methylaniline, m- and p-nitroaniline and m-methoxyaniline)
with the addition of acid catalyst (p-TsOH) and heathing in a sealed Teflon container
(autoclave). Compound 2 was synthesized from commercially available kojic acid. Acetylated
mannose derivatives (8-11) were obtained by Koenigs-Knorr glycosidation using 2,3,4,6-
tetra-O-acetyl-1-bromo-α-D-mannopyranose, collidine and AgOTf as promoter. The target
compounds, N-aryl 3-hydroxypyridin-4-one α-mannosides (13-16), were prepared by removal
of acetyl groups from mannose subunit in compounds 8-11 (Zemplén procedure). The
inhibitory activity of target molecules 13-16 in the E. coli adhesion to erythrocyte cells was
evaluated.
The structures of all prepared compounds were determined by NMR (1H i 13C)
spectroscopy and mass spectrometry (MS).

• Keywords: N-aril-3-hidroksipiridin-4-oni; FimH inhibitori; Koenigs-Knorrova metoda glikozidacije; kojična kiselina; manokonjugati
• Keywords (english): N-aryl 3-hydroxypyridin-4-ones; FimH inhibitors; glycosidation; Koenigs-Knorr method; kojic acid; mannoconjugates
• Language: croatian
• URN:NBN: urn:nbn:hr:217:046696
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2020-02-23
• Created on: 2018-03-23 13:51:18