New publication of COSM group : “Synthesis of Ether lipids: natural compounds and analogues”
M.A.G.B. Gomes, A. Bauduin, C. Le Roux, R. Fouinneteau, W. Berthe, M. Berchel, H. Couthon, P.A. Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299-1369 ; DOI: 10.3762/bjoc.19.96
Ether lipids are compounds present in many living organisms including humans that feature an ether bond linkage at the sn-1 position of the glycerol. This class of lipids features singular structural roles and biological functions. Alkyl ether lipids and alkenyl ether lipids (also identified as plasmalogens) correspond to the two sub-classes of naturally occurring ether lipids. The discovery in 1979 of the structure of the Platelet-Activating Factor (PAF) that belongs to the alkyl ether class of lipids increased the interest of these bio-active lipids and further promoted the synthesis of non-natural ether lipids that was initiated in the late 60’s with the development of Edelfosine (an anticancer drug). More recently, Ohmline, a glyco-glycero-ether lipid that modulates selectively SK3 ion channels and reduces in vivo the occurrence of bone metastases, and other glycol-glycero ether also identified as GAEL (Glycosylated Antitumor Ether Lipids) that exhibit promising anticancer-properties renew the interest of this class of compounds. Indeed, ether-lipid represent a new and promising class of compounds featuring the capacity to modulate selectively the activity of some membrane proteins or, for other compounds, feature antiproliferative properties via an original mechanism of action. The increasing interest in studying ether lipids for fundamental and applied researches invited to review the methodologies developed to prepare ether lipids. In this review we focused on the synthetic method used for the preparation of alkyl ether lipids either naturally occurring ether lipids (e.g. PAF) or synthetic derivatives that were developed to study their biological properties. The synthesis of neutral or charged ether lipids are reported with the aim to assemble in this review the most frequently used methodologies to prepare this specific class of compounds.