Total synthesis of the lipid mediator PD1n-3 DPA: configurational assignments and anti-inflammatory and pro-resolving actions.
Total synthesis of the lipid mediator PD1n-3 DPA: configurational assignments and anti-inflammatory and pro-resolving actions.
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DOI：
10.1021/np4009865
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发表时间：
2014-04-25
影响因子：
5.1
通讯作者：
Hansen TV
中科院分区：
文献类型：
--
作者：
Aursnes M;Tungen JE;Vik A;Colas R;Cheng CY;Dalli J;Serhan CN;Hansen TV
最近从 5 和人类巨噬细胞的自消炎性渗出物中分离出多不饱和脂质介质 PD1n-3 DPA (5)。在此，PD1n-3 DPA (5) 的首次全合成经过 10 个步骤，总产率为 9%。这些努力，连同其甲酯6的NMR数据，证实了5的结构是(7Z,10R,11E,13E,15Z,17S,19Z)-10,17-二羟基二十二碳五烯酸。所提出的涉及环氧化物中间体的生物合成途径得到了捕获实验结果的支持。此外，从合成甲酯6的水解获得的游离酸5的LC-MS/MS数据与内源产生的生物材料的数据相匹配。天然产物 PD1n-3 DPA (5) 表现出强大的抗炎特性以及刺激人类巨噬细胞吞噬作用和胞吞作用的促消退作用。这些结果提供了关于 n-3 DPA 结构-功能的新知识，这些结构和功能越来越多的专门的促解决脂质介质和途径。
The polyunsaturated lipid mediator PD1n-3 DPA (5) was recently isolated from self-resolving inflammatory exudates of 5 and human macrophages. Herein, the first total synthesis of PD1n-3 DPA (5) is reported in 10 steps and 9% overall yield. These efforts, together with NMR data of its methyl ester 6, confirmed the structure of 5 to be (7Z,10R,11E,13E,15Z,17S,19Z)-10,17-dihydroxydocosa-7,11,13,15,19-pentaenoic acid. The proposed biosynthetic pathway, with the involvement of an epoxide intermediate, was supported by results from trapping experiments. In addition, LC-MS/MS data of the free acid 5, obtained from hydrolysis of the synthetic methyl ester 6, matched data for the endogenously produced biological material. The natural product PD1n-3 DPA (5) demonstrated potent anti-inflammatory properties together with pro-resolving actions stimulating human macrophage phagocytosis and efferocytosis. These results contribute new knowledge on the n-3 DPA structure–function of the growing numbers of specialized pro-resolving lipid mediators and pathways.
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影响因子：
4
作者：
Serhan, Charles N.;Chiang, Nan
通讯作者：
Chiang, Nan
影响因子：
62.1
作者：
Serhan, Charles N.;Petasis, Nicos A.
通讯作者：
Petasis, Nicos A.
影响因子：
4.4
作者：
Serhan, CN;Gotlinger, K;Petasis, NA
通讯作者：
Petasis, NA
DOI：
10.1084/jem.192.8.1197
发表时间：
2000-10-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Serhan CN;Clish CB;Brannon J;Colgan SP;Chiang N;Gronert K
通讯作者：
Gronert K
影响因子：
20.3
作者：
Dalli, Jesmond;Serhan, Charles N.
通讯作者：
Serhan, Charles N.