Sinteza i karakterizacija hibrida 3-supstituiranih beta-karbolina i ferocena povezanih 1,2,3-triazolskim prstenom

master's thesis

• Title (english): Synthesis and characterization of hybrids of 3-substituted beta-carbolines and ferrocenes linked by 1,2,3-riazole ring
• Author: Tina Šutalo
• Mentor: Ivana Perković (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Zrinka Rajić (član povjerenstva)
• Committee member: Miranda Sertić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2021-07-01, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

U ovom radu sintetizirana su i strukturno karakterizirana 2 nova hibridna spoja koji u svojoj strukturi
sadrže β-karbolinski prsten i ferocen, povezane 1H-1,2,3-triazolom, kao i prekursori potrebni za njihovu
sintezu, b-karbolinski azid 4 i b-karbolinski alkin 6, te ferocenazid 7, dok je etinilferocen nabavljen iz
komercijalnih izvora. b-karbolinski azid sintetiziran je u četiri reakcijska koraka. Pictet-Spenglerovom
kondenzacijom metilnog estera L-triptofana i acetaldehid-dimetil-acetala nastaje tetrahidro-bkarbolinski
međuprodukt 1 koji je oksidiran (aromatiziran) u odgovarajući b-karbolin s esterskom
skupinom na položaju 3. Redukcijom estera nastaje primarni alkohol koji je uz pomoć ADMP-a kao
donora azidne skupine uz DBU preveden u b-karbolinski azid 4. Sinteza alkina u položaju C3 β-
karbolinskog prstena nastavlja se od primarnog alkohola 3. Oksidacijom alkohola te reakcijom nastalog
aldehida i Bestmann-Ohirinog reagensa nastaje b-karbolinski alkin 6. Ferocenazid 7 je sintetiziran u
jednom reakcijskom koraku. Alkololna skupina ferocenmetanola se prevodi u azido uz ADMP u
bazičnim uvjetima. Za povezivanje b-karbolinskog azida 4 i etinilferocena, te b-karbolinskog alkina 6 i
ferocenazida 7 u hibridne spojeve 8 i 9, korištena je bakrom (I) katalizirana azid-alkin cikloadicija koja
rezultira stvaranjem triazolskog prstena, poveznice između b-karbolinskog prstena i ferocena. Strukture
sintetiziranih spojeva potvrđene su spektroskopskim i spektrometrijskim metodama (1H i 13C NMR, IR,
MS). U daljnjim istraživanjima bit će ispitano biološko djelovanje sintetiziranih hibridnih spojeva.

Abstract (english)

Two new hybrid compounds, 8 and 9, consisting of β-carboline and ferrocene moieties, connected via
1H-1,2,3-triazole, have been synthesized and structurally characterized, as well as precursors required
for their synthesis, b-carboline azide 4, b-carboline alkyne 6, and ferrocenazide 7, while
ethynylferrocene was obtained from commercial sources. b-carboline azide has been sythesized in a
four steps procedure. Pictet-Spengler condensation of L-tryptophan with ADMA generated tetrahydrob-
carboline intermedier 1 which was subsequently oxidized to corresponding b-carboline ester 2.
Reduction of the ester gave the corresponding alcohol 3 which was converted to b-carboline azide 4 by
using ADMP under basic conditions (DBU). The synthesis of alkyne at the C3 position of the bcarboline
ring involves oxidation of the alcohol 3 to the aldehyde 5. Homologation of aldehyde with
dimethyl (1-diazo-2-oxopropyl) phosphonate in the presence of K2CO3 resulted in b-carboline alkyne 6.
Ferrocenazide 7 was synthesized in a one reaction step. The alcohol group of ferrocenmethanol was
converted to the azido using ADMP in the presence of DBU. The copper(I)-catalyzed azide-alkyne
cycloaddition was used as a method of choice for linking b-carboline azide 4 and ethynylferrocene or
β-carboline alkyne 6 and ferrocenazide 7, into hybrid compounds 8 and 9, respectively. As a result, a
triazole ring was formed. The structures of the prepared compounds were confirmed by analytical and
spectroscopic methods (1H and 13C NMR, IR, MS). In further studies, the biological activity of the
synthesized hybrid compounds, will be investigated.

• Keywords: β-karbolin; ferocen; hibridni spoj; 1H-1; 2; 3-triazol; sinteza
• Keywords (english): β-carboline; ferrocene; hybrid compounds; 1; 2; 3-triazole; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:934647
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-07-01
• Created on: 2022-02-28 13:13:42