Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid.

The first total synthesis of a docosahexaenoic acid (DHA)-like methoxylated ether lipid (MEL) is reported. This compound constitutes an all- methylene skipped hexaene framework identical to that present in DHA, the well-known omega-3 polyunsaturated fatty acid. The polyene C22 hydrocarbon chain, bearing a methoxyl group in the 2-position and -configuration at the resulting chiral center, is attached by an ether linkage to the hydroxymethyl group (-1 position) of a glycerol backbone.

Asymmetric Synthesis of Methoxylated Ether Lipids: A Glyceryl Glycidyl Ether Key Building Block Design, Preparation, and Synthetic Application.

The report describes the preparation and use of a double-C3 building block intended as a head group synthon in the synthesis of saturated, mono-, and polyunsaturated 1--alkyl--glycerol type methoxylated ether lipids (MELs). The resulting head piece, an enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, was accomplished in 49% yield (max 50%) from a 1:1 diastereomeric mixture obtained from -solketal and racemic epichlorohydrin after treatment with the Jacobsen (,)-Co(III)salen catalyst for the hydrolytic kinetic resolution of terminal epoxides. The diol hydrolytic product obtained in 47% yield from the unwanted diastereomer was reconverted into epoxide with an inversion of configuration in a three-step operation involving a highly regioselective lipase.