Kinetička rezolucija fluoriranih alkohola katalizirana lipazama

master's thesis

• Title (english): Kinetic resolution of fluoroalcohols catalysed by lipases
• Author: Valentina Ević
• Mentor: Maja Majeric Elenkov (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Jasmina Rokov Plavec (član povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Ivana Biljan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2019-02-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Optički čisti spojevi su vrijedni prekursori u farmaceutskoj industriji. Fluorirani spojevi su
aktivne tvari u mnogim lijekovima, stoga su nove mogućnosti sinteze fluoriranih kiralnih
graĎevnih blokova posebno zanimljive i vrijedne. U ovom radu sintetizirana su tri racemična
derivata 1-fluorpropan-2-ola koji su supstituirani u položaju 3 azido (1a), cijano (2a)
skupinom i klorom (3a) te su korišteni kao supstrati za kinetičku rezoluciju kataliziranu
lipazama. Pripravljeni su i odgovarajući racemični acetati alkohola (1b-3b) kao standardi. U
ovim reakcijama ispitano je pet različitih lipaza. Najaktivnije i najselektivnije lipaze za
pojedini alkohol testirane su u različitim organskim otapalima. Lipaze su pokazale nisku do
srednje visoku enantioselektivnost prema ispitanim supstratima (E = 1 – 44). U preparativnim
reakcijama kataliziranim lipazama najviše enantioselektivnosti, pripravljeni su enantiomerno
obogaćeni produkti: (R)-1a (ev = 65 – 85 %), (S)-1b (ev = 92 %), (R)-2a (ev = 84 %), (S)-2b
(ev = 68 %) te smjesa (S)-3a (ev = 30 %) i (R)-3b (ev = 69 %).

Abstract (english)

Optically pure compunds are valuable precursors in pharmaceutical industry. Active
ingridients in many drugs are fluorinated compounds, therefore the new possibilities in
synthesis of fluorinated chiral building blocks are especially interesting and valuable. In this
thesis three racemic derivatives of 1-fluoropropan-2-ol were synthesized, substituated at
position 3 with azide (1a), cyanide (2a) and chloride (3a) and used as substrates in lipasecatalyzed
kinetic resolution. Corresponding racemic acetates were prepared (1b-3b) as
standards. Five different lipases were tested. Lipase with highest activity and selectivity with
each alcohol was tested in different organic solvents. Lipases have shown low to high
enantioselectivity toward supstrates (E = 1 – 44). In preparative-scale reactions catalysed by
lipases with highest enantioselectivity, enantiomerically enriched products were prepared:
(R)-1a (ee = 65 – 85 %), (S)-1b (ee = 92 %), (R)-2a (ee = 84 %), (S)-2b (ee = 68 %), and
mixture of (S)-3a (ee = 30 %) and (R)-3b (ee = 69 %).

• Keywords: fluoroalkoholi; halogenhidrin dehalogenaza; kinetička rezolucija; kiralni spojevi; lipaze
• Keywords (english): chiral compunds; fluoroalcohols; halohydrin dehalogenase; kinetic resolution; lipases
• Language: croatian
• URN:NBN: urn:nbn:hr:217:807825
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-03-07 11:01:53