Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of a Triene C18 : 3 Omega-8 MEL Derivative

The asymmetric synthesis of a triene C18 : 3 n-8 methoxylated ether lipid (MEL) of the 1-O-alkyl-sn-glycerol type is described by two different routes. The C18 : 3 hydrocarbon chain is attached by an ether linkage to the pro-S hydroxymethyl group of the glycerol backbone, and constitutes an all-cis methylene skipped triene framework, along with a methoxyl group in the 2’-position and R-configuration at the resulting chiral centre. The initial synthesis was based on the polyacetylene approach involving a semi-hydrogenation of the resulting triyne. A modified approach based on a combined polyacetylene-Wittig strategy was also successfully executed and an attempt made to compare and evaluate these strategies. Both syntheses were started from our previously described enantio- and diastereomerically pure isopropylidene-protected glyceryl glycidyl ether, a double-C3 building block designed as a head group synthon for synthesis of various types of MELs which was shown to suit the Wittig-based approach very well.