Sinteza i karakterizacija novih derivata tetrahidropirolo[3,4-b]indola s propargilnom i tert-butilnom esterskom skupinom, kao prekursora hibridnih molekula s potencijalnim antimalarijskim djelovanjem

master's thesis

• Title (english): Synthesis and characterization of new derivatives of tetrahydropyrrolo[3,4-b]indole with propargyl and tert-butyl ester groups as precursors of hybrid molecules with potential antimalarial activity
• Author: Lucija Sente
• Mentor: Ivana Perković (mentor)
• Mentor: Matija Gredičak (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Mirela Matić (član povjerenstva)
• Committee member: Matija Gredičak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2024-11-19, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Malarija je infektivna bolest tropskih i subtropskih krajeva koja svake godine bilježi porast mortaliteta, a nemogućnost
kontrole širenja bolesti predstavlja veliki izazov. Ovaj rad obuhvaća sintezu i karakterizaciju novih derivata
tetrahidropirolo[3,4-b]indola s propargilnom i tert-butilnom esterskom skupinom, kao prekursora hibridnih molekula s
potencijalnim antimalarijskim djelovanjem. Izabrani izocijanidni derivati dobiveni su iz odgovarajućih aminokiselina.
Propargilni esteri DL-alanina i L-fenilalanina (8, 13) pripravljeni su u 3 koraka, dok je tert-butilni ester DL-alanina (3)
pripravljen u jednom sintetskom koraku. Potom je amino-skupina pripravljenih estera (3, 8, 13) prevedena u
formamidnu, a u posljednjem koraku formamidi su prevedeni u odgovarajuće izocijanidne derivate (5, 10, 15). Dobiveni
spojevi (16, 17, 18) korišteni su u reakciji dearomatizacije N-tosil-3-nitroindola (2) koji je prethodno pripravljen iz
indola u 2 koraka. Zbog nestabilnosti spojeva dobivenih dearomatizacijom provedena je in situ redukcija uz NaBH3CN.
U daljnjim istraživanjima, koja prelaze okvire ovog rada, click-reakcijom propargilne skupine pripravljenog spoja i
molekule koja sadrži funkcionalnu skupinu azid sintetizirat će se novi hibridni spojevi potencijalnog anitmalarijskog
djelovanja.

Abstract (english)

Malaria is an infectious disease found in tropical and subtropical regions, which records an annual increase in mortality,
and the inability to control the spread of the disease presents a major challenge. This paper covers the synthesis and
characterization of new derivatives of tetrahydropyrrolo[3,4-b]indole with propargyl and tert-butyl ester groups as
precursors of hybrid molecules with potential antimalarial activity. The selected isocyanide derivatives were obtained
from the corresponding amino acids. Propargyl esters of DL-alanine and L-phenylalanine (8, 13) were prepared in three
steps, while the tert-butyl ester of DL-alanine (3) was synthesized in a single synthetic step. The amino group of the
prepared esters (3, 8, 13) was then converted to a formamide group, and in the final step, the formamides were converted
into the corresponding isocyanide derivatives (5, 10, 15). The obtained compounds (16, 17, 18) were used in the
dearomatization reaction of N-tosyl-3-nitroindole (2), which was previously synthesized from indole in two steps. Due
to the instability of the compounds obtained through dearomatization, in situ reduction was performed using NaBH3CN.
In further research, beyond the scope of this work, new hybrid compounds with potential antimalarial activity will be
synthesized by performing a click reaction between the propargyl group of the prepared compound and a molecule
containing an azide functional group.

• Keywords: tetrahidropirolo[3; 4-b]indol; izocijanoester; malarija
• Keywords (english): tetrahydropyrrolo[3; 4-b]indole; isocyanoester; malaria
• Language: croatian
• URN:NBN: urn:nbn:hr:163:295087
• 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: 2026-11-19
• Created on: 2025-02-05 14:21:01