prikaz prve stranice dokumenta Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora
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master's thesis
Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora
Zagreb: University of Zagreb, Faculty of Science, 2020. urn:nbn:hr:217:796237
Radošević, Ela
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Radošević, E. (2020). Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:796237

Radošević, Ela. "Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora." Master's thesis, University of Zagreb, Faculty of Science, 2020. https://urn.nsk.hr/urn:nbn:hr:217:796237

Radošević, Ela. "Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora." Master's thesis, University of Zagreb, Faculty of Science, 2020. https://urn.nsk.hr/urn:nbn:hr:217:796237

Radošević, E. (2020). 'Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora', Master's thesis, University of Zagreb, Faculty of Science, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:796237

Radošević E. Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2020 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:217:796237

E. Radošević, "Asimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:217:796237

Metadata
TitleAsimetrična alilna dearomatizacija u sintezi potencijalnih kinaznih inhibitora
Title (english)Asymmetric allylic dearomatization reaction in potential kinase inhibitor synthesis
AuthorEla Radošević
MentorSanja Koštrun (mentor)
Committee memberInes Primožič (predsjednik povjerenstva)
Committee memberIva Juranović Cindrić (član povjerenstva)
Committee memberŽeljka Soldin (član povjerenstva)
Committee memberIvan Kodrin (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2020-11-27, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Abstract
SRC-kinaze su enzimi koji su uključeni u regulaciju mnogobrojnih staničnih funkcija, od rasta, diobe, metabolizma, pa do apoptoze stanica. U sklopu ovog diplomskog rada provedena je analiza literaturno dostupnih kristalnih struktura kompleksa poznatih inhibitora sa SRC-kinazom. Proučavnjem njihovih interakcija unutar aktivnog mjesta, metodom molekulskog uklapanja dizajnirani su njihovi analozi koji sadrže fragment bogat sp3 hibridiziranim ugljikovim atomima. Za sintezu su odabrani spojevi koji su imali najbolje rezultate u molekularnom uklapanju te je za njih provedena retrosintetska analiza. Nadalje, provedena je višestupanjska sinteza spoja N-benzil-6-brom-4-vinil-1,3,4,9-tetrahidro-β-karbolina temeljena na reakciji asimetrične alilne dearomatizacije katalizirane iridijem. Zatim su sintetizirani fragmenti ponatiniba i PP2 liganda te je 3-etinilimidazo[1,2-b]piridazinski fragment ponatiniba uspješno povezan s sp3 bogatim fragmentom, dok sinteza analoga jednog od najaktivnijih inhibitora SRC kinaza, PP2 liganda, nije bila uspješna.
Abstract (english)
SRC-kinases are enzymes that are involved in many cellular functions, from cell growth, division and metabolism to cell apoptosis. In this diploma thesis analysis of literally available crystal structures of SRC-kinase with different inhibitors was performed. By studying interactions between active site and known inhibitors, by means of molecular docking method, new analogues that contain a fragment rich in sp3 hybridized carbon atoms were designed. Compounds with the best docking scores were chosen for the synthesis and the retrosynthetic analysis of selected compounds was successfully done. Furthermore, in this diploma thesis N-benzyl-6-bromo-4-vinyl-1,3,4,9-tetrahydro-β-carboline was prepared in five steps relaying on iridium catalyzed asymmetric allyl dearomatization. Hinge binder fragments of ponatinib and PP2 ligand were synthesized and 3-ethynylimidazo[1,2-b]pyridazine fragment was successfully coupled to sp3 rich fragment. Synthesis of the PP2 analogue, one of the most active SRC-kinase inhibitors, was not successful.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:796237
Study programmeTitle: 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 resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2020-12-10 13:15:20