Efnasmíðar á metoxyl setnum eterlípíðum og n-3 PUFA / Syntheses of methoxylated ether lipids and n-3 PUFA - verkefni lokið
Fréttatilkynning verkefnisstjóra
The strategy that was followed is based on copper promoted sequential condensations of terminal acetylenes with propargyl halides and attaching a diyne head group to an appropriate mono-, di-, tri- or tetrayne tail part, depending on the target molecule, regardless of whether synthesizing the polyunsaturated MELs or n-3 PUFAs.
The chief objectives of the project were total syntheses of various saturated, mono- and polyunsaturated methoxylated ether lipids (MELs) found in the liver oil of shark and elasmobranch fish and the omega-3 polyunsaturated fatty acids (n-3 PUFAs) that are characteristic of marine fat. These tasks were based on a modified methodology that we previously developed supported by IRF for the total synthesis of a remarkable n-3 polyunsaturated MEL discovered in the liver oil of the Greenland shark. That fascinating natural product constitutes the hexaene n-3 framework found in docosahexaenoic acid (DHA), one of the two most prevalent n-3 PUFAs in fish and marine fat.
Heiti
verkefnis: Efnasmíðar á metoxyl setnum eterlípíðum og n-3 PUFA / Syntheses of
methoxylated ether lipids and n-3 PUFA
Verkefnisstjóri: Guðmundur G. Haraldsson, Raunvísindastofnun Háskólans
Tegund styrks: Verkefnisstyrkur
Styrkár: 2012-2014
Fjárhæð styrks: 19,93 millj. kr. alls
Tilvísunarnúmer Rannís: 12002302
The strategy that was followed is based on
copper promoted sequential condensations of terminal acetylenes with propargyl
halides and attaching a diyne head group to an appropriate mono-, di-, tri- or
tetrayne tail part, depending on the target molecule, regardless of whether
synthesizing the polyunsaturated MELs or n-3 PUFAs. The synthesis may be
divided into three parts: (a) synthesis of a diyne head group; (b) synthesis of
a polyyne tail part; (c) attachment of the head group and tail part, and a
subsequent stereoselective partial hydrogenation to induce the all-cis methylene interrupted polyene
framework.
We managed to develop a highly efficient synthetic methodology to synthesize polyyne precursors to the polyunsaturated MELs and the n-3 PUFAs and their successful conversion into the intended target compounds. Current work supported by IRF aims at improving the key stereoselective partial hydrogenation step, where the polyynes are converted into their corresponding polyenes.
It is anticipated that syntheses of various polyunsaturated bioactive lipids and lipid mediators, isotopic labeling and structure elucidation of unknown lipids will benefit from the synthetic methodology developed in this project. The project has resulted in submission of four Master theses and it is clear that several peer-reviewed publications will emerge from this work in the near future.
