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

Abstract

AbstractThe 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.