Sinteza propargilnih epoksida i njihova rezolucija halogenhidrin-dehalogenazama

doctoral thesis

• Title (english): Synthesis of propargylic epoxides and their resolution by halohydrin dehalogenases
• Author: Robert Junior Kolman
• Mentor: Irena Dokli (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Antonija Tomić (član povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2024-12-09, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Raznovrsna reaktivnost uslijed prisustva ugljik-ugljik trostruke veze čini propargil-epokside vrijednim građevnim blokovima u organskoj sintezi. Međutim, postoji malo opisanih metoda za njihovu pripravu. Halogenhidrin-dehalogenaze (HHDH) su enzimi koji kataliziraju pretvorbu halogenhidrina i epoksida u oba smjera. U okviru ove doktorske disertacije sintetizirane su dvije serije racemičnih terminalnih propargil-epoksida. Spojevi su sintetizirani s različitim brojem, položajem i vrstom supstituenata. Time je istražena mogućnost upotrebe propargil-epoksida kao supstrata HHDH u reakcijama kinetičke rezolucije. Pokazano je da su aromatima monosupstituirani te disupstituirani spojevi dobri supstrati, dok alifatima monosupstituirani nisu. Najbolji supstrati iz skupine aromatskih te disupstituiranih spojeva upotrijebljeni su za sintezu optički čistih propargilnih azidoalkohola na preparativnoj skali. Na optički čistim spojevima provedene su reakcije postmodifikacija te je dobiven spoj koji sadrži dihidrofuranil-triazolni motiv koji se nalazi u spojevima s poznatim biološkim aktivnostima.

Abstract (english)

Due to the presence of a carbon-carbon triple bond, propargylic epoxides are valuable building blocks in organic synthesis. However, known methods for their synthesis are scarce. Halohydrin dehalogenases (HHDH) are enzymes that facilitate the conversion of epoxides and halohydrins in both directions. Within this dissertation, two series of racemic terminal propargylic epoxides were synthesized. The number, position and type of substituents was varied. The use of propargylic epoxides as substrates in kinetic resolution reactions catalyzed by HHDHs was investigated. It was demonstrated that the aromatic monosubstituted and disubstituted compounds are good substrates, whereas the aliphatic monosubsituted compounds are not. The best performing aromatic monosubstituted and disubstituted compounds were used for synthesis of optically pure propargylic azido alcohols on a preparative scale. Optically pure compounds were then transformed in post-modification reactions. A compound containing the dihydrofuranyl triazole motif, found in compounds with known biological activities, was obtained.

• Keywords: biokataliza; cinkom katalizirana Grignardova reakcija; halogenhidrin-dehalogenaze; kinetička rezolucija; propargil-alkoholi; propargil-epoksidi; triazoli
• Keywords (english): biocatalysis; halohydrin dehalogenases; kinetic resolution; propargylic alcohols; propargylic epoxides; triazoles; zinc-catalyzed Grignard reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:217:367925
• Promotion: 2024
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica u području prirodnih znanosti (doktor/doktorica u području prirodnih znanosti)
• Type of resource: Text
• Extent: LXXII, 115 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-12-13 13:31:15