magistrsko delo
Luka Jedlovčnik (Author), Janez Košmrlj (Mentor), Matija Strlič (Thesis defence commission member), Janez Cerkovnik (Thesis defence commission member)

Abstract

Magistrsko delo opisuje sintezo 5-devteropirimidin-4-karboksilne kisline. Devterij smo uvedli na mesto 5 v obroču, kar bi lahko omogočilo preučevanje sekundarnega kinetičnega izotopskega efekta pri delovanju encima orotidin 5′-monofosfat dekarboksilaze (OMPDC), ki katalizira reakcijo dekarboksilacije pri pretvorbi orotidin 5′-monofosfata (OMP) v uridin 5′-monofosfat (UMP). Ta reakcija predstavlja zadnjo stopnjo v biosintezi nukleotidov pri parazitu Plasmodium falciparum, odgovornemu za večino smrtnih primerov malarije pri človeku. Sintezo smo izvedli v treh korakih, kjer smo najprej karboksilno skupino pretvorili v orto usmerjajočo amidno skupino. V naslednjem koraku smo z organolitijevim reagentom deprotonirali molekulo na mestu 5 in s sledečo elektrofilno substitucijo s težko vodo v molekulo uvedli devterij. V zadnjem koraku smo z bazično hidrolizo amidno skupino pretvorili nazaj v karboksilno funkcionalno skupino in s tem izolirali končno, 5-devteropirimidin-4-karboksilno kislino. V procesu sinteze smo kot usmerjajočo skupino preizkusili tudi estrsko funkcionalno skupino, a pri tem devteriranje ni poteklo. Nastala je nova, v literaturi še neopisana spojina, N,N-diizopropil-5-(pirimidin-4-karbonil)pirimidin-4-karboksamid. Obe sintetizirani spojini smo okarakterizirali z NMR tehnikami, IR spektroskopijo, meritvijo tališča in masno spektrometrijo visoke ločljivosti. Sintetizirana 5-devteropirimidin-4-karboksilna kislina je bila poslana partnerjem na projektu na Queen's University v Kingstonu (Ontario, Kanada), ki bodo izvedli študije reakcijske kinetike in sekundarnega kinetičnega izotopskega efekta.

Keywords

organska sinteza;devteriranje;usmerjeno orto-metaliranje;areni;kinetični izotopski efekt;malarija;magistrska dela;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
Publisher: [L. Jedlovčnik]
UDC: 547.853(043.2)
COBISS: 125707523 Link will open in a new window
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Downloads: 17
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Other data

Secondary language: English
Secondary title: Towards the synthesis of 5-deuteropyrimidine-4-carboxylic acid
Secondary abstract: This thesis describes the synthesis of 5-deuteropyrimidine-4-carboxylic acid. Deuterium was introduced at the site 5 in the ring, which could allow the study of a secondary kinetic isotope effect in the action of the enzyme orotidine 5′-monophosphate decarboxylase (OMPDC), which catalyses the decarboxylation reaction in the conversion of orotidine 5′-monophosphate (OMP) to uridine 5′-monophosphate (UMP). This reaction represents the final step in nucleotide biosynthesis in the Plasmodium falciparum parasite, which is responsible for most of the fatal cases of malaria in humans. The synthesis was carried out in three steps, first converting the carboxyl group to an ortho-directing amide group. In the next step, the molecule was deprotonated at the site 5 using an organolithium reagent and deuterium was introduced into the molecule by subsequent electrophilic substitution with heavy water. In the final step, the amide group was converted back to the carboxyl functional group by basic hydrolysis and the final 5-deuteropyrimidine-4-carboxylic acid was isolated. The ester functional group was also tried as a directing group in the synthesis process, but no deuteration took place. A new compound, N,N-diisopropyl-5-(pyrimidin-4-carbonyl)pyrimidin-4-carboxamide, not yet described in the literature, was obtained. Both synthesised compounds were characterised by NMR techniques, IR spectroscopy, melting point measurement and high resolution mass spectrometry. The synthesised 5-deuteropyrimidine-4-carboxylic acid was sent to the project partners at Queen's University in Kingston (Ontario, Canada) to carry out studies on reaction kinetics and the secondary kinetic isotope effect.
Secondary keywords: pyrimidine;deuteration;directed ortho-metalation;kinetic isotope effect;organic synthesis;Pirimidini;Univerzitetna in visokošolska dela;
Type (COBISS): Master's thesis/paper
Study programme: 1000375
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo, smer Kemija
Pages: 53 str.
ID: 16345644