Enantioselektivna sinteza optički aktivnih 2-oksazolidinona i alkohola katalizirana halogenhidrin-dehalogenazama

doctoral thesis

• Title (english): Enantioselective synthesis of optically active 2-oxazolidinones and alcohols catalysed by halohydrin dehalogenases
• Author: Ana Mikleušević; VIAF: 12146574004338102690
• Mentor: Maja Majerić-Elenkov (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Maja Majerić-Elenkov (član povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2016-04-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Sažetak
Dvije halogenhidrin-dehalogenaze (HheC i HheA-N178A) potrebne za provođenje biokatalitičkih transformacija pripravljene su u obliku sirovog enzimskog ekstrakta. Pripravljeni su racemični epoksidi, oksazolidinoni, azidoalkoholi, cijanoalkoholi i bromalkoholi koji su korišteni kao supstrati i/ili standardi za enzimske reakcije.Razvijene su metode tekućinske kromatografije visoke djelotvornosti i plinske kromatografije na kolonama s kiralnim nepokretnim fazama za praćenje tijeka, regio- i enantioselektivnosti reakcija. Ispitana je kinetička i dinamička kinetička rezolucija racemičnih epibromhidrina i utjecaj dodanog natrijevog bromida u enzimskim reakcijama s različitim nukleofilima (cijanat, cijanid, azid kataliziranima halogenhidrin-dehalogenazom HheC. Dobiveni rezultati pokazali su da je HheC efikasan katalizator za pripravu odgovarajućih oksazolidinona u visokom iskorištenju i visoke enantiomerne čistoće. Ispitana je katalitička aktivnost genetski modificirane halogenhidrin-dehalogenaze HheA-N187A u reakcijama azidolize racemičnih aromatskih epoksida. Kao rezultat ovog istraživanja, novim biokatalitičkim postupkom pripravljeni su optički čisti 2-oksazolidinoni i β-azidoalkoholi te je dobiven bolji uvid u katalitičku aktivnost, regioselektivnost i enantioselektivnost ispitanih halogenhidrin-dehalogenaza.

Abstract (english)

A crude enzyme extracts of two halohydrin dehalogenases(HheC and HheA-N178A) for biocatalytic transformations with different substrates have been prepared. Racemic epoxides, oxazolidinones, azidoalcohols, cyanohydrins and bromoalcohols for substrates and/or standards for enzymatic reactions have been synthesized. Analytical methods of high performance liquid chromatography and gas chromatography on columns with chiral stationary phases for monitoring conversion, regio- and enantioselectivity of enzymatic reactions have been developed. Kinetic and dinamic kinetic resolution of racemic epibromohydrins in enzymatic reactions with different nucleophiles (cyanate, cyanide and azide) catalysed by halohydrin dehalogenase HheC have been studied. Catalytic activity of genetically modified halohydrin dehalogenase HheA-N178A in reactions of azidolysis of aromatic epoxides has been explored. As a result of this research, optically active 2-oxazolidinones and β-azidoalcohols have been prepared via biocatalytic reactions. A brighter insight in catalytic activity, regioselectivity and enantioselectivity of tested halohydrin dehalogenases has been given.

• Keywords: dinamička kinetička rezolucija; epoksidi; halogenhidrin-dehalogenaze; kinetička rezolucija; oksazolidinoni; β-azidoalkoholi
• Keywords (english): dinamic kinetic resolution; epoxides; halohydrin-dehalogenases; kinetic resolution; oxazolidinones; β-azidoalcohols
• Language: croatian
• URN:NBN: urn:nbn:hr:217:908286
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 104 str. ; 30 cm
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2019-03-21 13:15:29