Lipids from the marine world: Perspectives of an organic chemist

This report describes synthesis of novel structured triacylglycerols (TAGs) and diacylglyceryl ethers (DAGEs) of the 1-O-alkyl-sn-glycerol type constituting EPA and DHA as the sole fatty acids. One of two TAGs was comprised of a pure EPA located at the 1,3-positions with pure DHA at the 2-position and the other had it reversed with a pure DHA at the 1,3-positions and pure EPA at the 2-positions. The similarly structured DAGEs were derived from chimyl-, batyl-, and selachyl alcohols constituting pure EPA at their sn-3 position with pure DHA at the sn-2 position as well as the opposite composition with pure DHA at the sn-3 position and EPA at the sn-2 position, the total of six such DAGE products. The syntheses of these compounds were brought about by a two-step chemoenzymatic process involving a highly regioselective immobilized Candida antarctica lipase to incorporate EPA or DHA activated as acetoxime esters exclusively into the 1,3-positions of glycerol and the sn-3 position of the 1-O-alkyl-sn-glycerols. The second PUFA acyl groups were subsequently introduced to the remaining 2-positions by EDCI coupling agent to accomplish the title compounds highly efficiently in very high to excellent yields (86–92%). Practical applications: The work described is based on a previously reported methodology to introduce n-3 PUFAs activated as oxime esters exclusively into the terminal 1,3-positions of glycerol and 1-O-alkyl-sn-glycerols to prepare reversed structured TAGs and DAGEs by use of immobilized Candida antarctica lipase. The methodology is ideal for introducing isotopically labeled fatty acids into predetermined positions of TAGs and DAGEs. Novel structured triacylglycerols (TAGs) and diacylglyceryl ethers (DAGEs), constituting EPA and DHA as the sole fatty acids, were obtained by a two-step chemoenzymatic synthesis comprised of an exclusive incorporation of EPA or DHA, activated as acetoxime esters, into the terminal positions of glycerol and 1-O-alkyl-sn-glycerols by use of immobilized Candida antarctica lipase, and a subsequent introduction of a second PUFA acyl group to the remaining 2-positions by EDCI coupling agent.