Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of Polyunsaturated C18:3 Omega-3 and Omega-6 MEL Triene Derivatives

The asymmetric synthesis of polyunsaturated triene C18:3 n-3 and C18:3 n-6 methoxylated ether lipids (MEL) of the 1- -alkyl- -glycerol type is described as possible structural candidates for a triene C18:3 MEL of an unknown identity found in a mixture of shark and dogfish liver oil. Their C18:3 hydrocarbon chains constitute an all- methylene skipped n-3 or n-6 triene framework, along with a methoxyl group at the 2'-position and -configuration of the resulting stereogenic center. The methoxylated polyenes are attached by an ether linkage to the hydroxymethyl group of the glycerol backbone. The syntheses were based on the polyacetylene approach that involves a semi-hydrogenation of the resulting triynes. Both syntheses were started from our previously described enantio- and diastereomerically pure isopropylidene-protected glyceryl glycidyl ether, a double-C3 building block that was designed as a head group synthon for the synthesis of various types of MELs.