Total synthesis of 2-(5,6-epoxyisoprostane A2)phosphorylcholine and elucidation of the relative configuration of the isoprostane moiety
Total synthesis of 2-(5,6-epoxyisoprostane A2)phosphorylcholine and elucidation of the relative configuration of the isoprostane moiety
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DOI：
10.1002/anie.200500534
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Kobayashi, Y
中科院分区：
文献类型：
--
作者：
Acharya, HP;Kobayashi, Y
1-棕榈酰-2-（5，6-环氧异前列烷E2）-sn-甘油基-3-磷酸胆碱（1）和相关分子2与5，在sn-2位的6-环氧异前列烷A2（方案1）是1-棕榈酰-2-花生四烯酸酰-sn-甘油基-3-磷酸胆碱（PAPC）[1]的氧化产物，其在白细胞介素-1 β刺激的人主动脉内皮细胞（HAEC）和轻度氧化的低密度脂蛋白（ox-LDL）。[2]这些分子刺激HAEC释放白细胞介素-8和单核细胞趋化蛋白-1。由这些趋化因子激活的单核细胞[2，3]进入血管壁，在那里它们启动并导致动脉粥样硬化病变的进展。[3，4] 1和2的整个结构，特别是异前列烷单元的乙烯基环氧化物部分，对于该活性是重要的。[5]In与这些化合物的生物学研究取得的相当大的进展相反，1和2的环氧异前列烷部分的结构尚未完全阐明。因此，尽管环氧和Δ14烯烃部分的连接性和几何结构已经通过1H NMR光谱和质谱法明确地确定，[1] Δ7烯烃的E几何结构和相对构型仍然存在。
1-Palmitoyl-2-(5, 6-epoxyisoprostane E2)-sn-glycero-3-phosphorylcholine (1) and the related molecule 2 with 5, 6-epoxyisoprostane A2 at the sn-2 position (Scheme1) are oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC)[1] that are found in interleukin-1β-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.[5]In contrast to the considerable progress made in the biological study of these compounds, the structures of the epoxyisoprostane parts of 1 and 2 had not been elucidated fully. Thus, although the connectivities and geometries of the epoxy and Δ14 olefinic moieties had been determined unambiguously by 1H NMR spectroscopy and mass spectrometry,[1] the E geometry of the Δ7 alkene and the relative configura-