dc.contributor.advisor | Stenstrøm, Yngve | |
dc.contributor.advisor | Nolsøe, Jens M. J. | |
dc.contributor.advisor | Hansen, Trond Vidar | |
dc.contributor.advisor | Antonsen, Simen | |
dc.contributor.author | Gjessing, Gard | |
dc.date.accessioned | 2018-06-21T13:20:57Z | |
dc.date.available | 2018-06-21T13:20:57Z | |
dc.date.issued | 2018 | |
dc.identifier.uri | http://hdl.handle.net/11250/2502550 | |
dc.description.abstract | I denne oppgaven ble det utviklet en syntese av (3R,5Z,8Z,11Z,14Z,17Z)-3-hydroksieikosa-5,8,11,14,17-pentaensyre (3(R)-HEPE), et 3(R)-hydroksi-oksilipin biosyntetisert fra (5Z,8Z,11Z,14Z,17Z)-eikosa-5,8,11,14,17-pentaensyre (EPA) av visse gjær-arter. Det er påvist at den patogene gjæren Candida albicans er mindre virulent når den får hemmet biosyntesen av 3(R)-hydroksi-oksilipiner. Biologisk testing av 3(R)-HEPE vil kunne avdekke hvordan disse forbindelsene biosyntetiseres, og hvordan biosyntesen kan blokkeres.
Utgangsstoffet i syntesen av 3(R)-HEPE, etyl (4Z,7Z,10Z,13Z,16Z,19Z)-dokosa-4,7,10,13,16,19-heksaenat (DHA-EE), ble omdannet til et C18-aldehyd. Dette aldehydet ble addert til et N-acetyl-tioksotiazolidin i en Evans-Nagao acetat aldol-type reaksjon som gav to diastereomere aldolprodukter. Det ble oppnådd et 8:1 diastereomerforhold i favør av den ønskede diastereomeren med R-konfigurasjon ved karbinolgruppen. Omdannelse av tioksotiazolidin-substituenten til en hydroksylgruppe gav deretter målmolekylet 3(R)-HEPE. | nb_NO |
dc.description.abstract | A synthesis of 3(R)-HEPE, a 3(R)-hydroxy-oxylipin biosynthesized from (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoic acid (EPA) by certain yeast species, was developed in this thesis. It has been shown that the pathogenic yeast Candida albicans is less virulent when its biosynthesis of 3(R)-hydroxy-oxylipins is inhibited. Biological testing of 3(R)-HEPE may uncover how these compounds are biosynthesized, and how the biosynthesis can be inhibited.
The starting material in the synthesis of 3(R)-HEPE, ethyl (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenate (DHA-EE), was converted to a C18-aldehyde. This aldehyde was added to an N-acetyl-thioxothiazolidine in an Evans-Nagao acetate aldol-type reaction which afforded two diastereomeric aldol products. We achieved a diastereomeric ratio of 8:1 in favor of the desired diastereomer with an R-configured carbinol group. Converting the thioxothiazolidine substituent into a hydroxyl group then afforded the target molecule 3(R)-HEPE. | nb_NO |
dc.language.iso | nob | nb_NO |
dc.publisher | Norwegian University of Life Sciences, Ås | nb_NO |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.subject | Oksilipiner | nb_NO |
dc.subject | Candida albicans | nb_NO |
dc.subject | Acetat aldol | nb_NO |
dc.title | Syntese av 3(R)-HEPE via en Evans-Nagao acetat aldol-type reaksjon | nb_NO |
dc.title.alternative | Synthesis of 3(R)-HEPE via an Evans-Nagao acetate aldol-type reaction | nb_NO |
dc.type | Master thesis | nb_NO |
dc.description.version | submittedVersion | nb_NO |
dc.subject.nsi | VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440::Organisk kjemi: 441 | nb_NO |
dc.description.localcode | M-KJEMI | nb_NO |