Total Synthesis of 2-(5,6-Epoxyisoprostane A_2)phosphorylcholine and Elucidation of the Relative Configuration of the Isoprostane Moiety

摘要

1-Palmitoyl-2-(5,6-epoxyisoprostane E_2)-sn-glycero-3-phos-phorylcholine (1) and the related molecule 2 with 5,6-epoxyisoprostane A_2 at the sn-2 position (Scheme 1) are oxidation products of 1-palmitoyl-2-arachidonoyl-.w-glycero-3-phosphorylcholine (PAPC)'1' that are found in interleukin-1(3-stimulated human aortic endothelial cells (HAEC) and in mildly oxidized low-density lipoproteins (ox-LDL).[2] These molecules stimulate HAEC to release interleukin-8 and monocyte chemotactic protein-1.The monocytes activated by these chemokines'2'3' enter the vessel wall,where they initiate and cause the progression of atherosclerotic lesion.'3'4' The whole structures of 1 and 2,and in particular the vinyl epoxide moiety of the isoprostane unit,are important for this activity.