Synthesis of (Z)-(2′R)-1-O-(2′-methoxynonadec-10′-enyl)-sn-glycerol, a new analog of bioactive ether lipids

An unsaturated 2-methoxy-substituted 1-O-alkylglycerol, (Z)-(2′R)-1-O-(2′-methoxynonadec-10′-enyl)-sn-glycerol, a new analog of bioactive ether lipids, was synthesized from oleic acid and 2,3-isopropylidene-sn-glycerol. The two key steps of this synthesis were the conversion of oleyl aldehyde to a monounsaturated epoxide using Matteson’s method followed by hydrolytic kinetic resolution and a nucleophilic epoxide opening by 2,3-isopropylidene-sn-glycerol in the presence of potassium tert-butoxide in anhydrous DMF, which appeared to be a good reagent for this purpose. Furthermore, the diol by-product of the HKR process was also easily converted back to the starting epoxide thus almost doubling the amount of target molecule.

Graphical abstractAn unsaturated methyl glyceryl ether, analog of known antitumor derivatives was synthesized in seven steps from oleic acid. Diol by-product of an HKR process was also easily converted to epoxide with the required absolute configuration.Figure optionsDownload full-size imageDownload as PowerPoint slide