Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O. Box 1068, 0316 Oslo, Norway.
Lipid Mediator Unit, Center for Biochemical Pharmacology, William Harvey Research, Institute, Barts and The London School of Medicine, Queen Mary University of London Charterhouse Square, London EC1M 6BQ, U.K.
J Nat Prod. 2023 Nov 24;86(11):2546-2553. doi: 10.1021/acs.jnatprod.3c00769. Epub 2023 Oct 25.
The methyl ester of resolvin D5, a lipid mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid, was stereoselectively prepared in 8% yield over 12 steps (longest linear sequence). The key steps for the introduction of the two stereogenic secondary alcohols were an organocatalyzed oxyamination and the Midland Alpine borane reduction. For the assembly of the carbon chain, the Sonogashira cross-coupling reaction and the Takai olefination were utilized. The physical properties, including retention time in liquid chromatography and tandem mass spectra, of the synthetic material were matched against material from human peripheral blood and mouse infectious exudates. Synthetic RvD5, obtained just prior to biological experiments, displayed potent leukocyte-directed activities, upregulating the ability of neutrophils and macrophages to phagocytose bacteria, known as hallmark bioactions of specialized pro-resolving endogenous mediators.
消旋-5-去甲前列腺素 D5 的甲酯，一种由ω-3 脂肪酸 n-3 二十二碳五烯酸生物合成的脂质介质，通过 12 步（最长线性序列）以 8%的收率立体选择性合成。引入两个手性仲醇的关键步骤是有机催化的氧胺化和米德兰阿尔卑斯硼烷还原。为了组装碳链，利用了 Sonogashira 交叉偶联反应和 Takai 烯烃化反应。合成材料的物理性质，包括液相色谱和串联质谱中的保留时间，与来自人外周血和小鼠传染性渗出物的材料相匹配。在进行生物学实验之前获得的合成 RvD5 显示出强大的白细胞定向活性，上调了中性粒细胞和巨噬细胞吞噬细菌的能力，这是专门的促解决内源性介质的标志性生物作用。
