Synthesis of fish oil derived omega-3 polyunsaturated fatty acid analogs

Fish oil exerts its biological activity through the omega-3 polyunsaturated fatty acid (;Menhaden oil with an initial content of 16.4% EPA and 6.6% DHA was concentrated to 54.3% and 28.4% respectively using a urea fractionation procedure. EPA and DHA were subsequently obtained in 96.2-98.6% purity and 76.7-83.5% purity respectively by reversed-phase open column chromatography. The elution and extraction time of the PUFAs was 70 to 90 minutes.;Several analogs of eicosapentaenoic and docosahexaenoic acid were prepared. The first series of compounds included 1-eicosapentaenoyl-2,3-isopropylidene-sn-glycerol (EPA-SE), 1-eicosapentaenoyl-sn-glycerol (EPA-G), 1-eicosapentaenoyl-2,3-isopropylidene-sn-amide-glycerol (EPA-iGA) and 1-eicosapentaenoyl-sn-amide-glycerol (EPA-GA). The synthesis were carried out at room temperature and under nitrogen to minimize oxidative degradation of the unsaturated acyl chain. EPA-SE was synthesized by condensation of the fatty acyl chloride with isopropylidene glycerol. EPA-SE was then treated with 1 N HCl in 2-propanol as a solvent to prepare EPA-G. The yields of the compounds were 81.99% and 47.23% respectively. EPA-iGA was synthesized from fatty acyl chloride and amine glycerol. EPA-CA was then obtained using EPA-iGA as a starting material. They were obtained in 59.47% and 49.92% yield respectively.;The second series of compounds included the N-eicosapentaenoyl-L-alanine (EPA-ALA) and N-eicosapentaenoyl-L-alanyl ethyl ester (EPA-AE). EPA-ALA was synthesized by condensation of the eicosapentaenoyl chloride (1 g, 3.3 mmol) with L-alanine (1.5 g, 16.8 mmol). EPA-AE was obtained by esterification of EPA-ALA with ethanol at 60...