magistrsko delo
Ida Brcar (Author), Janez Košmrlj (Mentor), Helena Prosen (Thesis defence commission member), Martin Gazvoda (Thesis defence commission member)

Abstract

V magistrskem delu smo uporabili reakcijske pogoje Sonogashirove reakcije brez bakra v sintezah zdravilnih učinkovin iz aril kloridov oziroma bromidov ter terminalnih acetilenov kot izhodnih substratov. Aril kloridi predstavljajo lažje dostopno in cenejšo alternativo aril bromidom, aril bromidi pa aril jodidom. Ovira, ki zmanjša uporabo aril kloridov in bromidov v primerjavi z aril jodidi, je močnejša interakcija med bromidom oz. kloridom in aromatskim obročem in posledično nižja reaktivnost substratov v dotičnih reakcijah. V delu so predstavljeni aktualni industrijski postopki sinteze treh komercialnih zdravilnih učinkovin, ki v vsaj enem koraku zajemajo spajanje po Sonogashiri s souporabo bakra. Ta korak smo nadomestili s Sonogashirovo reakcijo brez bakra, ga po potrebi optimizirali ter tako pripravili izbrane intermediate oz. končne produkte zdravilnih učinkovin. V prvem delu smo reakcijske pogoje za pretvorbo izbranih aril bromidov preko Sonogashirove reakcije brez bakra uporabili pri sintezi zdravilne učinkovine Fenleuton. Za drugo farmacevtsko učinkovino smo si zastavili aplikacijo reakcijskih pogojev za pretvorbo aril bromidov preko Sonogashirove reakcije brez bakra v postopek sinteze zdravila za kandidiazo. Nato pa smo reakcijske pogoje Sonogashirove reakcije brez souporabe bakra uporabili za pretvorbo aril kloridov v postopku sinteze antagonista receptorja TRPV1. Reakcijski pogoji so bili po potrebi prilagojeni.

Keywords

reakcije spajanja;Sonogashirova reakcija brez bakra;zdravline učinkovine;fosfinski ligandi;paladij;magistrska dela;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
Publisher: [I. Brcar]
UDC: 547.057(043.2)
COBISS: 117023491 Link will open in a new window
Views: 87
Downloads: 20
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Other data

Secondary language: English
Secondary title: Application of copper-free Sonogashira reaction in the synthesis of active pharmaceutical ingredients
Secondary abstract: The aim of this master's thesis is to present the application of copper-free Sonogashira reaction conditions in the formation of active pharmaceutical ingredients, starting from aryl chlorides or bromides and terminal acetylenes as substrates. Aryl chlorides are an accessible and cheaper alternative to aryl bromides, the same as aryl bromides are to aryl iodides. The downside of using bromides and chlorides is their reactivity, which is strongly decreased because of the stronger interaction between the bromine and chlorine atom and the aromatic ring. In this master’s thesis current industrial processes for the synthesis of three active pharmaceutical ingredients are presented, which include at least one step of Sonogashira reaction with Pd/Cu co-catalysis. This step was replaced by a copper-free Sonogashira reaction procedure and was optimized when necessary. Selected intermediates or end products were prepared. Firstly, the reaction conditions for the conversion of aryl bromides via the copper-free Sonogashira reaction were applied to the synthesis of the active pharmaceutical ingredient Fenleuton. Secondly, the reaction conditions for the conversion of aryl bromides via the Sonogashira copper-free reaction were applied to a Candidiasis drug synthesis process. Finally, the copper-free Sonogashira reaction catalytic system for the cross-coupling of aryl chlorides and acetylenes was applied to the synthesis path of TRPV1 receptor antagonist. The reaction conditions were adapted to each case as needed.
Secondary keywords: copper-free Sonogashira coupling;active pharmaceutical ingredients;phosphine ligands;palladium;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: 58 str.
ID: 15841047