Synthesis of Enantiopure Reversed Structured Ether Lipids of the 1-O-Alkyl-sn-2,3-diacylglycerol Type

Abstract

This report describes the synthesis of reversed structured 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGEs) possessing a pure saturated even number fatty acid (C6:0–C16:0) at the sn-2 position along with a pure EPA or DHA located at the terminal sn-3 position of the glycerol backbone of chimyl, batyl and selachyl alcohols. These adducts were synthesized by a highly efficient two-step chemoenzymatic process involving an immobilized Candida antarctica lipase to introduce pure EPA and DHA activated as oxime esters exclusively to the sn-3 terminal position of enantiopure chimyl, batyl and selachyl alcohols in excellent yields. The saturated fatty acids were subsequently incorporated to the remaining sn-2 position of the resulting 3-monoacylglyceryl ethers (3-MAGEs) using EDAC coupling agent in the presence of DMAP in very high to excellent yields (85%–98%). No losses of enantiomeric composition were observed during these processes. The multiple utilities of the resulting focused library of reversed structured DAGEs are discussed including how such compounds may possibly be utilized within the pharmaceutical area.

Keywords

• diacylglyceryl ethers (DAGE)
• ether lipids
• structured lipids
• n-3 PUFA
• EPA
• DHA
• n-3 PUFA oxime esters
• lipase
• chemoenzymatic synthesis
• focused lipid library