Sinteza statina imobiliziranim enzimom u kontinuiranim reaktorima

master's thesis

• Title (english): Synthesis of statins by immobilized enzyme in continuous flow systems
• Author: Martina Batur
• Mentor: Ana Vrsalović Presečki (mentor)
• Committee member: Ana Vrsalović Presečki (predsjednik povjerenstva)
• Committee member: Domagoj Vrsaljko (član povjerenstva)
• Committee member: Anita Šalić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-20, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Statini su farmaceutici koji se koriste za snižavanje kolesterola u krvi i u prevenciji kardiovaskularnih bolesti. Enzim 2-deoksiriboza-5-fosfat aldolaza (DERA) je jedini poznati enzim koji sudjeluje u visokoselektivnoj reakciji aldolne adicije pri čemu nastaje laktol, važan prekursor za proizvodnju bočnog lanca statina. DERA katalizira reakciju sinteze
(3R, 5R)-6-kloro-3,5-dihidroksiheksanala (laktola) dvostrukom aldolnom adicijom acetaldehida (AA) i kloroacetaldehida (CAA). Cilj ovog diplomskog rada bio je provesti sintezu statina imobiliziranim enzimom DERA u različitim tipovima kontinuiranih reaktora volumena 300 i 600 μL te serijski spojenim reaktorima (2 x 300 μL), odnosno ispitati utjecaj različitih volumena i protoka na nastanak međuprodukta, 4-kloro-3-hidroksibutanala (4 C-Cl) i produkta, 6-kloro-3,5-dihidroksiheksanala (6 C-Cl) . Reakcija u reaktorima se provodila pri protocima; 2, 5 i 7 μL/min. Usporedbom procesnih pokazatelja u reaktorima, kao najbolji parametri uspješnosti dobiveni su: XCAA,max = 99,98 % i XCAA,max = 96,93 % u eksperimentima E2-1 (V = 600 μL, q = 2 μL/min) i E3-1 (V = 2 x 300 μL, q = 2 μL/min) pri većem vremenu zadržavanja (87,0 min) dok je najveća produktivnost procesa u iznosu
1,99 mM/min postignuta u eksperimentu E1-3 (V = 300 μL, q = 7 μL/min) pri vremenu zadržavanja od 12,4 min.

Abstract (english)

Statins are pharmaceuticals used to lower cholesterol in the blood and to prevent cardiovascular diseases. Enzyme 2-deoxyribose-5-phosphate aldolase (DERA) is the only known enzyme that participates in the highly selective aldol addition reaction in which lactol, an important precursor for statin side chain production, is formed. DERA catalyzes the synthesis reaction of (3R, 5R)-6-chloro-3,5-dihydroxyhexanal (lactol) by double aldol addition of acetaldehyde (AA) and chloroacetaldehyde (CAA). The aim of this work was to carry out the synthesis of statins with an immobilized enzyme DERA in different types of continuous reactors with volumes of 300 and 600 μL and in series connected reactors (2 x 300 μL), i.e. examine the influence of different volumes and flow rates on formation of the intermediate product, 4-chloro-3-hydroxybutanal (4 C-Cl) and the product, 6-chloro-3,5-dihydroxyhexanal (6 C-Cl). The reaction in the reactors was carried out at flow rates; 2, 5 and 7 μL/min.
By comparing the process indicators in the reactors, as the best performance parameters were obtained: XCAA,max = 99.98 % and XCAA,max = 96.93 % in experiments
E2-1 (V = 600 μL, q = 2 μL/min) and E3-1 (V = 2 x 300 μL, q = 2 μL/min) at a longer retention time (87.0 min), while the highest productivity of the process in the amount of
1.99 mM/min was achieved in experiment E1-3 (V = 300 μL, q = 7 μL/min) at a retention time of 12.4 min.

• Keywords: statini; 2-deoksiriboza-5-fosfat aldolaza; DERA; aldolna adicija; imobilizacija; kontinuirani reaktori
• Keywords (english): statins; 2-deoxyribose-5-phosphate aldolase; DERA; aldol addition; immobilization; continuous reactors
• Language: croatian
• URN:NBN: urn:nbn:hr:149:097730
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-10-01
• Created on: 2023-11-15 13:13:32