Synthesis towards ω-functionalized polyunsaturated fatty acid derivatives

Målet med oppgaven var å syntetisere (9Z,12Z,15Z)-metyl-18-hydroksi-2-metyloktadeka-9,12,15-trienat (1), (12Z,15Z)-metyl-18-hydroksi-2-metyloktadeka-12,15-dienat (23a) og (12Z,15Z)-metyl-18-metoksi-2-metyloktadeka-12,15-dienat (23b), som en del av et prosjekt om fettsyrers biokjemiske innvirkning på fiskehelse og metabolisme hos atlantisk laks (Salmo salar). Oppgaven omhandler to syntesestrategier, hvor de samme sentrale reaksjonene er felles. Dette innebærer koblingsreaksjoner med terminale alkyner og propargyl bromider basert på acetylenkjemi, innføring og fjerning av beskyttelsesgrupper og hydrogenering. Målsetningen for den første strategien var å syntetisere et ω-3,6,9 fettsyrederivat (målmolekyl 1), mens målsetningen for den andre strategien var å syntetisere ω-3,6 fettsyrederivatene (målmolekyl 23a og 23b). Målmolekylene er vist i figur 1.1, 1.2 og 1.3. For målmolekyl 1 bestod arbeidet i å syntetisere metyldek-9-ynat (13) og 3-brom-1-(trimetylsilyl)-1-propyn (17) som ble koblet sammen til metyl 13-(trimetylsilyl)trideka-9,12-diynat (12). Det var meningen at forbindelse 12 videre skulle syntetiseres til forbindelse 10. Det ble forsøkt å syntetisere 5-brompent-3-yn-1-ol (4) som da skulle kobles med forbindelse 10. Veien videre var ment å skulle være en lineær syntese fram mot målmolekyl 1. For målmolekylene 23a og 23b bestod arbeidet i å syntetisere butyn-3-ylacetat (30) og koble denne sammen med 3-brom-1-(trimetylsilyl)-1-propyn (17) for å danne 7-(trimetylsilyl)hepta-3,6-diyn-1-ylacetat (29). Videre ble hepta-3,6-diyn-1-ylacetat (28) syntetisert ved å fjerne beskyttelsesgruppen trimetylsilyl (TMS) som ble forsøkt koblet sammen med metyl 11-bromundekanat (27), for å danne metyl 18-acetoksioktadeka-12,15-diynat (26). Veien videre mot målmolekylene 23a og 23b var ment å skulle være en lineær syntese. The aim of this study was to synthesize (9Z,12Z,15Z)-methyl-18-hydroxy-2-methyloctadeca-9,12,15-trienoate (1), (12Z,15Z)-methyl-18-hydroxy-2-methyloctadeca-12,15-dienoate (23a) and (12Z,15Z)-methyl-18-metoxy-2-methyloctadeca-12,15-dienoate (23b) as a part of various studies of fatty acids impact on the health and metabolism in atlantic salmon (Salmo salar). This thesis deals with two synthesis strategies which are related to the same central reactions. This mainly involves coupling reactions with terminal alkynes and propargylic bromides, introduction/removal of protecting groups and hydrogenation. The goal of the first strategy was to synthesise a ω-3,6,9 fatty acid derivative (target molecule 1), while the goal of the second strategy was to synthesize ω-3,6 fatty acid derivatives (target molecules 23a and 23b). The target molecules are shown in figure 1.1, 1.2 and 1.3. To reach target molecule 1 the process consisted of synthesizing methyldec-9-ynoate (13) and 3-bromo-1-(trimethylsilyl)-1-propyne (17), which was coupled to form methyl 13-(trimethylsilyl)trideca-9,12-diynoate (12). The intention was that 12 would further react to form compound 10. An attempt to synthesise 5-bromopent-3-yn-1-ol (4) for coupling with compound 10 was also undertaken, and a linear approach to synthesise molecule 1 was planned. The production of target molecules 23a and 23b consisted of synthesizing butyn-3-yl acetate (30), which was coupled with 3-bromo-1-(trimethylsilyl)-1-propyne (17), to form 7-(trimethylsilyl)hepta-3,6-diyne-1-yl acetate (29). Futhermore, hepta-3, 6-diyne-1-yl acetate (28) was synthesized by removing the protecting group trimethylsilyl (TMS), which was an attempted coupling reaction, using methyl 11-bromoundecanoate (27) to form methyl 18- acetoxyoctadeca-12,15-diynoate (26). A linear approach to produce molecules 23a and 23b was also meant to be undertaken