Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages.
Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages.
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DOI：
10.1021/acs.jnatprod.5b00574
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发表时间：
2015-12-24
影响因子：
5.1
通讯作者：
Hansen TV
中科院分区：
文献类型：
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作者：
Aursnes M;Tungen JE;Colas RA;Vlasakov I;Dalli J;Serhan CN;Hansen TV
N-3多不饱和脂肪酸作为急性炎症消退阶段的底物，用于专门化的促消解脂质介质的生物合成。一个主要的例子是C22-二羟基-多不饱和脂肪酸保护素D1(1)。人15-脂氧合酶I型，通过立体选择性过程，以二十二碳六烯酸为底物，能够形成这种专门化的促进分解的脂质介体。在此，基于LC/MS-MS代谢脂质组学的结果，支持在人巨噬细胞中通过中间体16S，17S-环氧基保护素(5)进行1的生物合成。通过Katsuki-Sharpless环氧化反应，确定了C16和C17原子的手性，一次Z-选择性还原以及E-和Z-立体选择性的Wittig反应，得到了立体化学纯5。此外，还提供了非酶水解产物和16S，17S-环氧基保护素的半衰期的信息(5)。
The n-3 polyunsaturated fatty acids act as substrates during the resolution phase of acute inflammation for the biosynthesis of specialized pro-resolving lipid mediators. One premier example is the C22-dihydroxy-polyunsaturated fatty acid protectin D1 (1). The human 15-lipoxygenase type I, via stereoselective processes and with docosahexaenoic acid as the substrate, enables the formation of this specialized pro-resolving lipid mediator. Herein, based on results from LC/MS-MS metabololipidomics, support is presented for the apprehended biosynthesis of 1 in human macrophages occurs via the intermediate 16S,17S-epoxy-protectin (5). Stereochemical pure 5 was obtained using the Katsuki-Sharpless epoxidation protocol, establishing the chirality at the C16 and C17 atoms, one Z-selective reduction as well as E- and Z-stereoselective Wittig reactions. In addition, information on the non-enzymatic aqueous hydrolysis products and the half-life of 16S,17S-epoxy-protectin (5) is presented.