Sinteza i karakterizacija alkina tetrahidropirolo[3,4-b]indola, prekursora hibridnih spojeva s potencijalnim antimalarijskim djelovanjem

master's thesis

• Title (english): Synthesis and characterization of tetrahydropyrrolo[3,4- b]indole alkyne, a precursor of hybrid molecules with potential antimalarial activity
• Author: Ante Kuvačić
• Mentor: Ivana Perković (mentor)
• Mentor: Matija Gredičak (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Matija Gredičak (član povjerenstva)
• Committee member: Kristina Pavić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2025-04-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Malarija je po život opasna zarazna bolest uzrokovana parazitima roda Plasmodium koji se prenose ubodom zaraženih
komaraca roda Anopheles. Unatoč značajnom napretku u kontroli i liječenju bolesti, malarija i dalje predstavlja
ozbiljnu javnozdravstvenu prijetnju, osobito u tropskim i supstropskim područjima. Rezistencija na postojeće lijekove
je u porastu, zbog čega je istraživanje novih načina liječenja malarije nužno. Ovaj rad obuhvaća sintezu i
karakterizaciju derivata tricikličkog prstena tetrahidropirolo[3,4-b]indola s propargilnom esterskom skupinom kao
ishodišne molekule u sintezi novih hibridnih molekula s potencijalnim antimalarijskim djelovanjem. U svrhu priprave
takvog derivata, modificirani su i kondenzirani indolski prsten i aminokiselina L-fenilalanin, pri čemu je pripravljen
N-tosil nitroindol u dva sintetska koraka. Propargilni ester aminokiseline je pripravljen u tri koraka (5), zatim je
amino- skupina spoja 5 prevedena u izocijanidnu skupinu u dva koraka (7). Izocijanidom modificiran propargilni ester
L-fenilalanina 7 korišten je u dearomatizaciji prethodno pripravljenog N-tosil nitroindola (2) pri čemu je sintetiziran
konačni produkt s karakterističnim tetrahidropirolo[3,4-b]indolskim prstenom (8). Strukture svih sintetiziranih spojeva
potvrđene su standardnim spektroskopskim metodama (1H i 13C NMR). Dobivena molekula će se u budućim
istraživanjima koristiti kao alkinski prekursor u klik-reakciji s azidima 4-amino-7-klorokinolinskih derivata, pri čemu
će nastati hibridi s triazolskom poveznicom potencijalnog antimalarijskog djelovanja.

Abstract (english)

Malaria is a life-threatening infectious disease caused by Plasmodium parasites, transmitted through the bites of
infected Anopheles mosquitoes. Despite significant progress in disease control and treatment, malaria remains a
serious public health threat, particularly in tropical and subtropical regions. The increasing resistance to existing drugs
poses a major challenge, emphasizing the necessity for the synthesis of new antimalarial agents. This thesis
encompasses the synthesis and characterization of tetrahydropyrrolo[3,4-b]indole tricyclic ring derivatives with a
propargyl ester group as a starting molecule for the synthesis of new hybrid compounds with potential antimalarial
activity. To prepare such a derivative, modifications were made to the indole ring and the amino acid L-phenylalanine,
leading to the synthesis of N-tosyl nitroindole in two synthetic steps. The propargyl ester of the amino acid 5 was
synthesized in three steps, after which the amino group was converted into an isocyanide group in two steps. The
obtained isocyanide-modified propargyl ester of L-phenylalanine 7 was then used in the dearomatization of the
previously synthesized N-tosyl nitroindole (2), resulting in the synthesis of the final product featuring a characteristic
tetrahydropyrrolo[3,4-b]indole ring (8).

• Keywords: malarija; sinteza; 4-amino-7-klorokinolini; 1; 2; 3-triazol; tetrahidropirolo[3; 4-b]indol
• Keywords (english): malaria; synthesis; 4-amino-7-chloroquinolines; 1; 2; 3-triazole; tetrahydropyrrolo[3; 4-b]indole
• Language: croatian
• URN:NBN: urn:nbn:hr:163:510517
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2027-04-11
• Created on: 2025-04-22 12:55:48